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Sample records for doses predict poorer

  1. Somatic Complaints in Children with Anxiety Disorders and Their Unique Prediction of Poorer Academic Performance

    ERIC Educational Resources Information Center

    Hughes, Alicia A.; Lourea-Waddell, Brittany; Kendall, Philip C.

    2008-01-01

    The present study aimed to examine somatic complaints in children with anxiety disorders compared to non-anxious control children and whether somatic complaints predict poorer academic performance. The sample consisted of 108 children and adolescents (aged 8-14 years) assessed by a structured diagnostic interview: 69 with a principal (i.e., most…

  2. Somatic complaints in children with anxiety disorders and their unique prediction of poorer academic performance.

    PubMed

    Hughes, Alicia A; Lourea-Waddell, Brittany; Kendall, Philip C

    2008-06-01

    The present study aimed to examine somatic complaints in children with anxiety disorders compared to non-anxious control children and whether somatic complaints predict poorer academic performance. The sample consisted of 108 children and adolescents (aged 8-14 years) assessed by a structured diagnostic interview: 69 with a principal (i.e., most severe and/or interfering) anxiety disorder diagnosis and 39 non-anxious community controls. Established child and parent report measure of somatic complaints, anxiety, and internalizing symptoms were completed. The participants' primary teacher was used to assess academic performance. Findings indicated that children with anxiety disorders reported more somatic complaints than the non-anxious community controls. Furthermore, a greater frequency of somatic complaints uniquely predicted poorer academic performance beyond that accounted for by anxiety and internalizing symptoms based on both child and parent report measures. Knowledge about somatic complaints in children with anxiety disorders and their relation to academic functioning may allow for early identification and prevent academic problems.

  3. Increased marijuana use and gender predict poorer cognitive functioning in adolescents and emerging adults.

    PubMed

    Lisdahl, Krista M; Price, Jenessa S

    2012-07-01

    This study sought to characterize neuropsychological functioning in MJ-using adolescents and emerging adults (ages 18-26) and to investigate whether gender moderated these effects. Data were collected from 59 teens and emerging adults including MJ users (n = 23, 56% female) and controls (n = 35, 50% female) aged 18-26 (M = 21 years). Exclusionary criteria included independent Axis I disorders (besides SUD), and medical and neurologic disorders. After controlling for reading ability, gender, subclinical depressive symptoms, body mass index, and alcohol and other drug use, increased MJ use was associated with slower psychomotor speed/sequencing ability (p < .01), less efficient sustained attention (p < .05), and increased cognitive inhibition errors (p < .03). Gender significantly moderated the effects of MJ on psychomotor speed/sequencing ability (p < .003) in that males had a more robust negative relationship. The current study demonstrated that MJ exposure was associated with poorer psychomotor speed, sustained attention and cognitive inhibition in a dose-dependent manner in young adults, findings that are consistent with other samples of adolescent MJ users. Male MJ users demonstrated greater cognitive slowing than females. Future studies need to examine the neural substrates underlying with these cognitive deficits and whether cognitive rehabilitation or exercise interventions may serve as a viable treatments of cognitive deficits in emerging adult MJ users.

  4. Increased Marijuana Use and Gender Predict Poorer Cognitive Functioning in Adolescents and Emerging Adults

    PubMed Central

    Lisdahl, Krista M.; Price, Jenessa S.

    2014-01-01

    This study sought to characterize neuropsychological functioning in MJ-using adolescents and emerging adults (ages 18–26) and to investigate whether gender moderated these effects. Data were collected from 59 teens and emerging adults including MJ users (n = 23, 56% female) and controls (n = 35, 50% female) aged 18–26 (M = 21 years). Exclusionary criteria included independent Axis I disorders (besides SUD), and medical and neurologic disorders. After controlling for reading ability, gender, subclinical depressive symptoms, body mass index, and alcohol and other drug use, increased MJ use was associated with slower psychomotor speed/sequencing ability (p< .01), less efficient sustained attention (p< .05), and increased cognitive inhibition errors (p< .03). Gender significantly moderated the effects of MJ on psychomotor speed/sequencing ability (p< .003) in that males had a more robust negative relationship. The current study demonstrated that MJ exposure was associated with poorer psychomotor speed, sustained attention and cognitive inhibition in a dose-dependent manner in young adults, findings that are consistent with other samples of adolescent MJ users. Male MJ users demonstrated greater cognitive slowing than females. Future studies need to examine the neural substrates underlying with these cognitive deficits and whether cognitive rehabilitation or exercise interventions may serve as a viable treatments of cognitive deficits in emerging adult MJ users. PMID:22613255

  5. Sustain talk predicts poorer outcomes among mandated college student drinkers receiving a brief motivational intervention.

    PubMed

    Apodaca, Timothy R; Borsari, Brian; Jackson, Kristina M; Magill, Molly; Longabaugh, Richard; Mastroleo, Nadine R; Barnett, Nancy P

    2014-09-01

    Within-session client language that represents a movement toward behavior change (change talk) has been linked to better treatment outcomes in the literature on motivational interviewing (MI). There has been somewhat less study of the impact of client language against change (sustain talk) on outcomes following an MI session. This study examined the role of both client change talk and sustain talk, as well as therapist language, occurring during a brief motivational intervention (BMI) session with college students who had violated college alcohol policy (N = 92). Audiotapes of these sessions were coded using a therapy process coding system. A series of hierarchical regressions were used to examine the relationships among therapist MI-consistent and MI-inconsistent language, client change talk and sustain talk, as well as global measures of relational variables, and drinking outcomes. Contrary to prior research, sustain talk, but not change talk, predicted poorer alcohol use outcomes following the BMI at 3- and 12-month follow-up assessments. Higher levels of client self-exploration during the session also predicted improved drinking outcomes. Therapist measures of MI-consistent and MI-inconsistent language, and global measures of therapist acceptance and MI spirit were unrelated to client drinking outcomes. Results suggest that client sustain talk and self-exploration during the session play an important role in determining drinking outcomes among mandated college students receiving a BMI addressing alcohol use.

  6. Characteristics of Fibromyalgia Independently Predict Poorer Long‐Term Analgesic Outcomes Following Total Knee and Hip Arthroplasty

    PubMed Central

    Urquhart, Andrew G.; Hassett, Afton L.; Tsodikov, Alex; Hallstrom, Brian R.; Wood, Nathan I.; Williams, David A.; Clauw, Daniel J.

    2015-01-01

    Objective While psychosocial factors have been associated with poorer outcomes after knee and hip arthroplasty, we hypothesized that augmented pain perception, as occurs in conditions such as fibromyalgia, may account for decreased responsiveness to primary knee and hip arthroplasty. Methods A prospective, observational cohort study was conducted. Preoperative phenotyping was conducted using validated questionnaires to assess pain, function, depression, anxiety, and catastrophizing. Participants also completed the 2011 fibromyalgia survey questionnaire, which addresses the widespread body pain and comorbid symptoms associated with characteristics of fibromyalgia. Results Of the 665 participants, 464 were retained 6 months after surgery. Since individuals who met criteria for being classified as having fibromyalgia were expected to respond less favorably, all primary analyses excluded these individuals (6% of the cohort). In the multivariate linear regression model predicting change in knee/hip pain (primary outcome), a higher fibromyalgia survey score was independently predictive of less improvement in pain (estimate −0.25, SE 0.044; P < 0.00001). Lower baseline joint pain scores and knee (versus hip) arthroplasty were also predictive of less improvement (R2 = 0.58). The same covariates were predictive in the multivariate logistic regression model for change in knee/hip pain, with a 17.8% increase in the odds of failure to meet the threshold of 50% improvement for every 1‐point increase in fibromyalgia survey score (P = 0.00032). The fibromyalgia survey score was also independently predictive of change in overall pain and patient global impression of change. Conclusion Our findings indicate that the fibromyalgia survey score is a robust predictor of poorer arthroplasty outcomes, even among individuals whose score falls well below the threshold for the categorical diagnosis of fibromyalgia. PMID:25772388

  7. Greater attention problems during childhood predict poorer executive functioning in late adolescence.

    PubMed

    Friedman, Naomi P; Haberstick, Brett C; Willcutt, Erik G; Miyake, Akira; Young, Susan E; Corley, Robin P; Hewitt, John K

    2007-10-01

    Attention problems (behavior problems including inattention, disorganization, impulsivity, and hyperactivity) are widely thought to reflect deficits in executive functions (EFs). However, it is unclear whether attention problems differentially relate to distinct EFs and how developmental stability and change predict levels of EFs in late adolescence. We investigated, in an unselected sample, how teacher-rated attention problems from ages 7 to 14 years related to three correlated but separable EFs, measured as latent variables at age 17. Attention problems at all ages significantly predicted later levels of response inhibition and working memory updating, and to some extent set shifting; the relation to inhibiting was stronger than the relations to the other EFs or IQ. Growth models indicated that attention problems were quite stable in this age range, and it was the initial levels of problems, rather than their changes across time, that predicted later EFs. These results support the hypothesis that attention problems primarily reflect difficulties with response inhibition.

  8. Peer Victimization, Depressive Symptoms, and High Salivary Cortisol Predict Poorer Memory in Children

    ERIC Educational Resources Information Center

    Vaillancourt, Tracy; Duku, Eric; Becker, Suzanna; Schmidt, Louis A.; Nicol, Jeffrey; Muir, Cameron; MacMillan, Harriet

    2011-01-01

    The predictive relations of peer victimization, depressive symptoms, and salivary cortisol on memory in 168 children aged 12 at Time 1 (T1) were examined using a longitudinal design in which data were collected on four occasions over a 2-year period. Results indicated that: (1) peer victimization, depressive symptoms, and evening cortisol were…

  9. Anhedonia Predicts Poorer Recovery among Youth with Selective Serotonin Reuptake Inhibitor Treatment-Resistant Depression

    ERIC Educational Resources Information Center

    McMakin, Dana L.; Olino, Thomas M.; Porta, Giovanna; Dietz, Laura J.; Emslie, Graham; Clarke, Gregory; Wagner, Karen Dineen; Asarnow, Joan R.; Ryan, Neal D.; Birmaher, Boris; Shamseddeen, Wael; Mayes, Taryn; Kennard, Betsy; Spirito, Anthony; Keller, Martin; Lynch, Frances L.; Dickerson, John F.; Brent, David A.

    2012-01-01

    Objective: To identify symptom dimensions of depression that predict recovery among selective serotonin reuptake inhibitor (SSRI) treatment-resistant adolescents undergoing second-step treatment. Method: The Treatment of Resistant Depression in Adolescents (TORDIA) trial included 334 SSRI treatment-resistant youth randomized to a medication…

  10. Shorter Anogenital Distance Predicts Poorer Semen Quality in Young Men in Rochester, New York

    PubMed Central

    Mendiola, Jaime; Stahlhut, Richard W.; Jørgensen, Niels; Liu, Fan

    2011-01-01

    Background: In male rodents, anogenital distance (AGD) provides a sensitive and continuous correlate of androgen exposure in the intrauterine environment and predicts later reproductive success. Some endocrine-disrupting chemicals can alter male reproductive tract development, including shortening AGD, in both rodents and humans. Whether AGD is related to semen quality in human is unknown. Objective: We examined associations between AGD and semen parameters in adult males. Methods: We used multiple regression analyses to model the relationships between sperm parameters and two alternative measures of AGD [from the anus to the posterior base of the scrotum (AGDAS) and to the cephalad insertion of the penis (AGDAP)] in 126 volunteers in Rochester, New York. Results: AGDAS, but not AGDAP, was associated with sperm concentration, motility, morphology, total sperm count, and total motile count (p-values, 0.002–0.048). Men with AGDAS below (vs. above) the median were 7.3 times more likely (95% confidence interval, 2.5–21.6) to have a low sperm concentration (< 20 × 106/mL). For a typical study participant, sperm concentrations were 34.7 × 106/mL and 51.6 × 106/mL at the 25th and 75th percentiles of (adjusted) AGDAS. Conclusions: In our population, AGDAS was a strong correlate of all semen parameters and a predictor of low sperm concentration. In animals, male AGD at birth reflects androgen levels during the masculinization programming window and predicts adult AGD and reproductive function. Our results suggest, therefore, that the androgenic environment during early fetal life exerts a fundamental influence on both AGD and adult sperm counts in humans, as demonstrated in rodents. PMID:21377950

  11. C-C motif chemokine ligand 5 (CCL5) levels in gastric cancer patient sera predict occult peritoneal metastasis and a poorer prognosis.

    PubMed

    Wang, Tie; Wei, Yuzhe; Tian, Lining; Song, Hongjiang; Ma, Yan; Yao, Qian; Feng, Meiyan; Wang, Yanying; Gao, Meizhuo; Xue, Yingwei

    2016-08-01

    Gastric cancer is one of the most common cancers and the third leading cause of cancer death worldwide. A number of chemokines and cytokines play important roles in the progress of gastric cancer. The roles of C-C motif chemokine ligand 5 (CCL5) in gastric cancer remain unclear. Here, we retrospectively report an analysis of 105 patients with gastric cancer. Increased levels of CCL5 in circulation were correlated with more advanced T and N stages, poorly- or un-differentiated histological types, peritoneal metastasis, higher rates of residual tumor, and shorter survivals. Patients in the CCL5 High Group had stronger CCL5 immunohistochemistry (IHC) staining in tumor beds. Circulating CCL5 concentrations before surgery are a good biomarker for occult peritoneal metastasis. Elevated levels of serum CCL5, along with strong IHC CCL5 staining and poorly- or un-differentiated cancer are predictors for poorer outcomes. In conclusion, increased serum levels of CCL5 can be used to predict peritoneal dissemination and a poorer prognosis.

  12. An increased neutrophil-to-lymphocyte ratio predicts poorer survival following recurrence for patients with breast cancer

    PubMed Central

    Iwase, Toshiaki; Sangai, Takafumi; Sakakibara, Masahiro; Sakakibara, Junta; Ishigami, Emi; Hayama, Shouko; Nakagawa, Ayako; Masuda, Takahito; Tabe, Shunsuke; Nagashima, Takeshi

    2017-01-01

    The aim of the present study was to evaluate the association between changes in the neutrophil-to-lymphocyte ratio and the survival rate, as well as tumor subtype, in recurrent breast cancer. Patients with recurrent breast cancer following surgery were included in this study. NLR was calculated and compared between two time points: Pre-treatment and recurrence. The associations between the longitudinal NLR change, the NLR at the time of recurrence and overall survival following recurrence (OSrec) were evaluated. A total of 89 patients were evaluated. NLR increased by 0.59 at recurrence, as compared with the initial treatment (P<0.05). The triple negative (TN) type demonstrated 4.59 in NLR, which was the highest among the four subtypes at the time of recurrence (P<0.05). The highest change (an increase of 2.0) was observed in TN type cancer (P<0.05). Patients with high NLR upon recurrence demonstrated significantly shorter OSrec rates (P<0.05). On the other hand, patients with an NLR increased by more than a third quartile demonstrated a shorter OSrec rate (P=0.06). When adjusted by covariates, the NLR and tumor subtype were determined to be associated with OSrec (P<0.05). Therefore, an increased NLR predicts survival, even in patients with recurrent breast cancer, and the NLR is potentially useful as an inflammation marker for TN breast cancer.

  13. Dose-volume histogram prediction using density estimation.

    PubMed

    Skarpman Munter, Johanna; Sjölund, Jens

    2015-09-07

    Knowledge of what dose-volume histograms can be expected for a previously unseen patient could increase consistency and quality in radiotherapy treatment planning. We propose a machine learning method that uses previous treatment plans to predict such dose-volume histograms. The key to the approach is the framing of dose-volume histograms in a probabilistic setting.The training consists of estimating, from the patients in the training set, the joint probability distribution of some predictive features and the dose. The joint distribution immediately provides an estimate of the conditional probability of the dose given the values of the predictive features. The prediction consists of estimating, from the new patient, the distribution of the predictive features and marginalizing the conditional probability from the training over this. Integrating the resulting probability distribution for the dose yields an estimate of the dose-volume histogram.To illustrate how the proposed method relates to previously proposed methods, we use the signed distance to the target boundary as a single predictive feature. As a proof-of-concept, we predicted dose-volume histograms for the brainstems of 22 acoustic schwannoma patients treated with stereotactic radiosurgery, and for the lungs of 9 lung cancer patients treated with stereotactic body radiation therapy. Comparing with two previous attempts at dose-volume histogram prediction we find that, given the same input data, the predictions are similar.In summary, we propose a method for dose-volume histogram prediction that exploits the intrinsic probabilistic properties of dose-volume histograms. We argue that the proposed method makes up for some deficiencies in previously proposed methods, thereby potentially increasing ease of use, flexibility and ability to perform well with small amounts of training data.

  14. Prediction of the mortality dose-response relationship in man

    SciTech Connect

    Morris, M.D.; Jones, T.D.

    1987-01-01

    Based upon an extensive data base including 100 separate animal studies, an estimate of the mortality dose-response relationship due to continuous photon radiation is predicted for 70 kg man. The model used in this prediction exercise includes fixed terms accounting for effects of body weight and dose rate, and random terms accounting for inter- and intra-species variation and experimental error. Point predictions and 95% prediction intervals are given for the LD/sub 05/, LD/sub 10/, LD/sub 25/, LD/sub 50/, LD/sub 75/, LD/sub 90/, and LD/sub 95/, for dose rates ranging from 1 to 50 R/min. 6 refs., 5 tabs.

  15. Quantifying and Communicating Uncertainty in Preclinical Human Dose-Prediction

    PubMed Central

    Sundqvist, M; Lundahl, A; Någård, MB; Bredberg, U; Gennemark, P

    2015-01-01

    Human dose-prediction is fundamental for ranking lead-optimization compounds in drug discovery and to inform design of early clinical trials. This tutorial describes how uncertainty in such predictions can be quantified and efficiently communicated to facilitate decision-making. Using three drug-discovery case studies, we show how several uncertain pieces of input information can be integrated into one single uncomplicated plot with key predictions, including their uncertainties, for many compounds or for many scenarios, or both. PMID:26225248

  16. Comprehensive fluence model for absolute portal dose image prediction.

    PubMed

    Chytyk, K; McCurdy, B M C

    2009-04-01

    Amorphous silicon (a-Si) electronic portal imaging devices (EPIDs) continue to be investigated as treatment verification tools, with a particular focus on intensity modulated radiation therapy (IMRT). This verification could be accomplished through a comparison of measured portal images to predicted portal dose images. A general fluence determination tailored to portal dose image prediction would be a great asset in order to model the complex modulation of IMRT. A proposed physics-based parameter fluence model was commissioned by matching predicted EPID images to corresponding measured EPID images of multileaf collimator (MLC) defined fields. The two-source fluence model was composed of a focal Gaussian and an extrafocal Gaussian-like source. Specific aspects of the MLC and secondary collimators were also modeled (e.g., jaw and MLC transmission factors, MLC rounded leaf tips, tongue and groove effect, interleaf leakage, and leaf offsets). Several unique aspects of the model were developed based on the results of detailed Monte Carlo simulations of the linear accelerator including (1) use of a non-Gaussian extrafocal fluence source function, (2) separate energy spectra used for focal and extrafocal fluence, and (3) different off-axis energy spectra softening used for focal and extrafocal fluences. The predicted energy fluence was then convolved with Monte Carlo generated, EPID-specific dose kernels to convert incident fluence to dose delivered to the EPID. Measured EPID data were obtained with an a-Si EPID for various MLC-defined fields (from 1 x 1 to 20 x 20 cm2) over a range of source-to-detector distances. These measured profiles were used to determine the fluence model parameters in a process analogous to the commissioning of a treatment planning system. The resulting model was tested on 20 clinical IMRT plans, including ten prostate and ten oropharyngeal cases. The model predicted the open-field profiles within 2%, 2 mm, while a mean of 96.6% of pixels over all

  17. Predicting Pneumonitis Risk: A Dosimetric Alternative to Mean Lung Dose

    SciTech Connect

    Tucker, Susan L.; Mohan, Radhe; Liengsawangwong, Raweewan; Martel, Mary K.; Liao Zhongxing

    2013-02-01

    Purpose: To determine whether the association between mean lung dose (MLD) and risk of severe (grade {>=}3) radiation pneumonitis (RP) depends on the dose distribution pattern to normal lung among patients receiving 3-dimensional conformal radiation therapy for non-small-cell lung cancer. Methods and Materials: Three cohorts treated with different beam arrangements were identified. One cohort (2-field boost [2FB]) received 2 parallel-opposed (anteroposterior-posteroanterior) fields per fraction initially, followed by a sequential boost delivered using 2 oblique beams. The other 2 cohorts received 3 or 4 straight fields (3FS and 4FS, respectively), ie, all fields were irradiated every day. The incidence of severe RP was plotted against MLD in each cohort, and data were analyzed using the Lyman-Kutcher-Burman (LKB) model. Results: The incidence of grade {>=}3 RP rose more steeply as a function of MLD in the 2FB cohort (N=120) than in the 4FS cohort (N=138), with an intermediate slope for the 3FS group (N=99). The estimated volume parameter from the LKB model was n=0.41 (95% confidence interval, 0.15-1.0) and led to a significant improvement in fit (P=.05) compared to a fit with volume parameter fixed at n=1 (the MLD model). Unlike the MLD model, the LKB model with n=0.41 provided a consistent description of the risk of severe RP in all three cohorts (2FB, 3FS, 4FS) simultaneously. Conclusions: When predicting risk of grade {>=}3 RP, the mean lung dose does not adequately take into account the effects of high doses. Instead, the effective dose, computed from the LKB model using volume parameter n=0.41, may provide a better dosimetric parameter for predicting RP risk. If confirmed, these findings support the conclusion that for the same MLD, high doses to small lung volumes ('a lot to a little') are worse than low doses to large volumes ('a little to a lot').

  18. Predicting dose-time profiles of solar energetic particle events using Bayesian forecasting methods.

    PubMed

    Neal, J S; Townsend, L W

    2001-12-01

    Bayesian inference techniques, coupled with Markov chain Monte Carlo sampling methods, are used to predict dose-time profiles for energetic solar particle events. Inputs into the predictive methodology are dose and dose-rate measurements obtained early in the event. Surrogate dose values are grouped in hierarchical models to express relationships among similar solar particle events. Models assume nonlinear, sigmoidal growth for dose throughout an event. Markov chain Monte Carlo methods are used to sample from Bayesian posterior predictive distributions for dose and dose rate. Example predictions are provided for the November 8, 2000, and August 12, 1989, solar particle events.

  19. Warfarin Dose Model for the Prediction of Stable Maintenance Dose in Indian Patients.

    PubMed

    Gaikwad, Tejasvita; Ghosh, Kanjaksha; Avery, Peter; Kamali, Farhad; Shetty, Shrimati

    2017-01-01

    The main aim of this study was to screen various genetic and nongenetic factors that are known to alter warfarin response and to generate a model to predict stable warfarin maintenance dose for Indian patients. The study comprised of 300 warfarin-treated patients. Followed by extensive literature review, 10 single-nucleotide polymorphisms, that is, VKORC1-1639 G>A (rs9923231), CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), FVII R353Q (rs6046), GGCX 12970 C>G (rs11676382), CALU c.*4A>G (rs1043550), EPHX1 c.337T>C (rs1051740), GGCX: c.214+597G>A (rs12714145), GGCX: 8016G>A (rs699664), and CYP4F2 V433M (rs2108622), and 5 nongenetic factors, that is, age, gender, smoking, alcoholism, and diet, were selected to find their association with warfarin response. The univariate analysis was carried out for 15 variables (10 genetic and 5 nongenetic). Five variables, that is, VKORC1-1639 G>A, CYP2C9*2, CYP2C9*3, age, and diet, were found to be significantly associated with warfarin response in univariate analysis. These 5 variables were entered in stepwise and multiple regression analysis to generate a prediction model for stable warfarin maintenance dose. The generated model scored R(2) of .67, which indicates that this model can explain 67% of warfarin dose variability. The generated model will help in prescribing more accurate warfarin maintenance dosing in Indian patients and will also help in minimizing warfarin-induced adverse drug reactions and a better quality of life in these patients.

  20. Detailed dose distribution prediction of Cf-252 brachytherapy source with boron loading dose enhancement.

    PubMed

    Ghassoun, J; Mostacci, D; Molinari, V; Jehouani, A

    2010-02-01

    The purpose of this work is to evaluate the dose rate distribution and to determine the boron effect on dose rate distribution for (252)Cf brachytherapy source. This study was carried out using a Monte Carlo simulation. To validate the Monte Carlo computer code, the dosimetric parameters were determined following the updated TG-43 formalism and compared with current literature data. The validated computer code was then applied to evaluate the neutron and photon dose distribution and to illustrate the boron loading effect.

  1. Genetic Risk Score Modelling for Disease Progression in New-Onset Type 1 Diabetes Patients: Increased Genetic Load of Islet-Expressed and Cytokine-Regulated Candidate Genes Predicts Poorer Glycemic Control

    PubMed Central

    Brorsson, Caroline A.; Nielsen, Lotte B.; Andersen, Marie Louise; Kaur, Simranjeet; Bergholdt, Regine; Hansen, Lars; Mortensen, Henrik B.; Pociot, Flemming; Størling, Joachim; Hvidoere Study Group on Childhood Diabetes

    2016-01-01

    Genome-wide association studies (GWAS) have identified over 40 type 1 diabetes risk loci. The clinical impact of these loci on β-cell function during disease progression is unknown. We aimed at testing whether a genetic risk score could predict glycemic control and residual β-cell function in type 1 diabetes (T1D). As gene expression may represent an intermediate phenotype between genetic variation and disease, we hypothesized that genes within T1D loci which are expressed in islets and transcriptionally regulated by proinflammatory cytokines would be the best predictors of disease progression. Two-thirds of 46 GWAS candidate genes examined were expressed in human islets, and 11 of these significantly changed expression levels following exposure to proinflammatory cytokines (IL-1β + IFNγ + TNFα) for 48 h. Using the GWAS single nucleotide polymorphisms (SNPs) from each locus, we constructed a genetic risk score based on the cumulative number of risk alleles carried in children with newly diagnosed T1D. With each additional risk allele carried, HbA1c levels increased significantly within first year after diagnosis. Network and gene ontology (GO) analyses revealed that several of the 11 candidate genes have overlapping biological functions and interact in a common network. Our results may help predict disease progression in newly diagnosed children with T1D which can be exploited for optimizing treatment. PMID:26904692

  2. Absorbed dose measurements on LDEF and comparisons with predictions.

    PubMed

    Benton, E V; Frank, A L; Benton, E R; Armstrong, T W; Colborn, B L

    1996-11-01

    The radiation environment on LDEF was monitored by cumulative absorbed dose measurements made with TLDs at different locations and shielding depths. The TLDs were included in four experiments: A0015(a) Biostack, P0004 Seeds in Space and P0006 Linear Energy Transfer Spectrum Measurements at the trailing edge (west side) of the satellite; M0004 Fiber Optics Data Link at the leading edge (east side); and A0015(b) Biostack at the Earth side. The shielding depths varied between 0.48 and 15.4 g/cm2, Al equivalent. Both the directional dependence of trapped protons incident on the satellite and the shielding thickness were reflected in absorbed dose values. The trapped proton anisotropy was measured by TLDs at the east and west sides of LDEF. At the east side doses ranged from 2.10 to 2.58 Gy under shielding of 2.90 to 1.37 g/cm2 (M0004) while on the west side doses ranged from 2.66 to 6.48 Gy under shielding of 15.4 to 0.48 g/cm2 (P0006). The west side doses were more than a factor of two higher, where the vertical shielding thicknesses to space were equal. Other west side doses of 3.04 to 4.49 Gy under shielding of 11.7 to 3.85 g/cm2 (A0015(a)) and 2.91 to 6.64 Gy under shielding of 11.1 to 0.48 g/cm2 (P0004) generally agreed with the P0006 results. The Earth side doses of 2.41 to 3.93 Gy under shielding of 10.0 to 1.66 g cm2 (A0015(b)) were intermediate between the east side and west side doses. Calculations utilizing a model of trapped proton spectra were performed by Watts et al. (1993) and comparisons of dose measurement and calculations may be found in a companion paper (Armstrong et al., 1996).

  3. Absorbed dose measurements on LDEF and comparisons with predictions

    NASA Technical Reports Server (NTRS)

    Benton, E. V.; Frank, A. L.; Benton, E. R.; Armstrong, T. W.; Colborn, B. L.

    1996-01-01

    The radiation environment on LDEF was monitored by cumulative absorbed dose measurements made with TLDs at different locations and shielding depths. The TLDs were included in four experiments: A0015(a) Biostack, P0004 Seeds in Space and P0006 Linear Energy Transfer Spectrum Measurements at the trailing edge (west side) of the satellite; M0004 Fiber Optics Data Link at the leading edge (east side); and A0015(b) Biostack at the Earth side. The shielding depths varied between 0.48 and 15.4 g/cm2, Al equivalent. Both the directional dependence of trapped protons incident on the satellite and the shielding thickness were reflected in absorbed dose values. The trapped proton anisotropy was measured by TLDs at the east and west sides of LDEF. At the east side doses ranged from 2.10 to 2.58 Gy under shielding of 2.90 to 1.37 g/cm2 (M0004) while on the west side doses ranged from 2.66 to 6.48 Gy under shielding of 15.4 to 0.48 g/cm2 (P0006). The west side doses were more than a factor of two higher, where the vertical shielding thicknesses to space were equal. Other west side doses of 3.04 to 4.49 Gy under shielding of 11.7 to 3.85 g/cm2 (A0015(a)) and 2.91 to 6.64 Gy under shielding of 11.1 to 0.48 g/cm2 (P0004) generally agreed with the P0006 results. The Earth side doses of 2.41 to 3.93 Gy under shielding of 10.0 to 1.66 g cm2 (A0015(b)) were intermediate between the east side and west side doses. Calculations utilizing a model of trapped proton spectra were performed by Watts et al. (1993) and comparisons of dose measurement and calculations may be found in a companion paper (Armstrong et al., 1996).

  4. Can point doses predict volumetric dose to rectum and bladder: a CT-based planning study in high dose rate intracavitary brachytherapy of cervical carcinoma?

    PubMed Central

    Patil, V M; Patel, F D; Chakraborty, S; Oinam, A S; Sharma, S C

    2011-01-01

    Objective Point doses, as defined by the International Commission on Radiation Units and Measurements (ICRU), are classically used to evaluate doses to the rectum and bladder in high dose rate intracavitary brachytherapy (HDR-ICBT) in cervical cancer. Several studies have shown good correlation between the ICRU point doses and the volumetric doses to these organs. In the present study we attempted to evaluate whether this correlation could be used to predict the volumetric doses to these organs. Methods A total of 150 HDR-ICBT insertions performed between December 2006 and June 2008 were randomly divided into two groups. Group A (n=50) was used to derive the correlation between the point and volumetric doses using regression analysis. This was tested in Group B (n=100) insertions using studentised residuals and Bland–Altman plots. Results Significant correlations were obtained for all volumetric doses and ICRU point doses for rectum and bladder in Group A insertions. The strongest correlation was found for the dose to 2 cc volumes (D2cc). The correlation coefficients for bladder and rectal D2cc versus the respective ICRU point doses were 0.82 and 0.77, respectively (p<0.001). Statistical validation of equations generated in Group B showed mean studentised residual values of 0.001 and 0.000 for the bladder and rectum. However, Bland–Altman analysis showed that the error range for these equations for bladder and rectum were ±64% and ±41% of the point A dose, respectively, which makes these equations unreliable for clinical use. Conclusion Volumetric imaging is essential to obtain proper information about volumetric doses. PMID:21511749

  5. Predicting Maintenance Doses of Vancomycin for Hospitalized Patients Undergoing Hemodialysis

    PubMed Central

    El Nekidy, Wasim S; El-Masri, Maher M; Umstead, Greg S; Dehoorne-Smith, Michelle

    2016-01-01

    Background Methicillin-resistant Staphylococcus aureus is a leading cause of death in patients undergoing hemodialysis. However, controversy exists about the optimal dose of vancomycin that will yield the recommended pre-hemodialysis serum concentration of 15–20 mg/L. Objective To develop a data-driven model to optimize the accuracy of maintenance dosing of vancomycin for patients undergoing hemodialysis. Methods A prospective observational cohort study was performed with 164 observations obtained from a convenience sample of 63 patients undergoing hemodialysis. All vancomycin doses were given on the floor after completion of a hemodialysis session. Multivariate linear generalized estimating equation analysis was used to examine independent predictors of pre-hemodialysis serum vancomycin concentration. Results Pre-hemodialysis serum vancomycin concentration was independently associated with maintenance dose (B = 0.658, p < 0.001), baseline pre-hemodialysis serum concentration of the drug (B = 0.492, p < 0.001), and interdialytic interval (B = −2.133, p < 0.001). According to the best of 4 models that were developed, the maintenance dose of vancomycin required to achieve a pre-hemodialysis serum concentration of 15–20 mg/L, if the baseline serum concentration of the drug was also 15–20 mg/L, was 5.9 mg/kg with interdialytic interval of 48 h and 7.1 mg/kg with interdialytic interval of 72 h. However, if the baseline pre-hemodialysis serum concentration was 10–14.99 mg/L, the required dose increased to 9.2 mg/kg with an interdialytic interval of 48 h and 10.0 mg/kg with an interdialytic interval of 72 h. Conclusions The maintenance dose of vancomycin varied according to baseline pre-hemodialysis serum concentration of the drug and interdialytic interval. The current practice of targeting a pre-hemodialysis concentration of 15–20 mg/L may be difficult to achieve for the majority of patients undergoing hemodialysis. PMID:27826151

  6. SU-E-T-802: Verification of Implanted Cardiac Pacemaker Doses in Intensity-Modulated Radiation Therapy: Dose Prediction Accuracy and Reduction Effect of a Lead Sheet

    SciTech Connect

    Lee, J; Chung, J

    2015-06-15

    Purpose: To verify delivered doses on the implanted cardiac pacemaker, predicted doses with and without dose reduction method were verified using the MOSFET detectors in terms of beam delivery and dose calculation techniques in intensity-modulated radiation therapy (IMRT). Methods: The pacemaker doses for a patient with a tongue cancer were predicted according to the beam delivery methods [step-and-shoot (SS) and sliding window (SW)], intensity levels for dose optimization, and dose calculation algorithms. Dosimetric effects on the pacemaker were calculated three dose engines: pencil-beam convolution (PBC), analytical anisotropic algorithm (AAA), and Acuros-XB. A lead shield of 2 mm thickness was designed for minimizing irradiated doses to the pacemaker. Dose variations affected by the heterogeneous material properties of the pacemaker and effectiveness of the lead shield were predicted by the Acuros-XB. Dose prediction accuracy and the feasibility of the dose reduction strategy were verified based on the measured skin doses right above the pacemaker using mosfet detectors during the radiation treatment. Results: The Acuros-XB showed underestimated skin doses and overestimated doses by the lead-shield effect, even though the lower dose disagreement was observed. It led to improved dose prediction with higher intensity level of dose optimization in IMRT. The dedicated tertiary lead sheet effectively achieved reduction of pacemaker dose up to 60%. Conclusion: The current SS technique could deliver lower scattered doses than recommendation criteria, however, use of the lead sheet contributed to reduce scattered doses.Thin lead plate can be a useful tertiary shielder and it could not acuse malfunction or electrical damage of the implanted pacemaker in IMRT. It is required to estimate more accurate scattered doses of the patient with medical device to design proper dose reduction strategy.

  7. Estimating the predictive quality of dose-response after model selection.

    PubMed

    Hu, Chuanpu; Dong, Yingwen

    2007-07-20

    Prediction of dose-response is important in dose selection in drug development. As the true dose-response shape is generally unknown, model selection is frequently used, and predictions based on the final selected model. Correctly assessing the quality of the predictions requires accounting for the uncertainties caused by the model selection process, which has been difficult. Recently, a new approach called data perturbation has emerged. It allows important predictive characteristics be computed while taking model selection into consideration. We study, through simulation, the performance of data perturbation in estimating standard error of parameter estimates and prediction errors. Data perturbation was found to give excellent prediction error estimates, although at times large Monte Carlo sizes were needed to obtain good standard error estimates. Overall, it is a useful tool to characterize uncertainties in dose-response predictions, with the potential of allowing more accurate dose selection in drug development. We also look at the influence of model selection on estimation bias. This leads to insights into candidate model choices that enable good dose-response prediction.

  8. Extrapolation of the dna fragment-size distribution after high-dose irradiation to predict effects at low doses

    NASA Technical Reports Server (NTRS)

    Ponomarev, A. L.; Cucinotta, F. A.; Sachs, R. K.; Brenner, D. J.; Peterson, L. E.

    2001-01-01

    The patterns of DSBs induced in the genome are different for sparsely and densely ionizing radiations: In the former case, the patterns are well described by a random-breakage model; in the latter, a more sophisticated tool is needed. We used a Monte Carlo algorithm with a random-walk geometry of chromatin, and a track structure defined by the radial distribution of energy deposition from an incident ion, to fit the PFGE data for fragment-size distribution after high-dose irradiation. These fits determined the unknown parameters of the model, enabling the extrapolation of data for high-dose irradiation to the low doses that are relevant for NASA space radiation research. The randomly-located-clusters formalism was used to speed the simulations. It was shown that only one adjustable parameter, Q, the track efficiency parameter, was necessary to predict DNA fragment sizes for wide ranges of doses. This parameter was determined for a variety of radiations and LETs and was used to predict the DSB patterns at the HPRT locus of the human X chromosome after low-dose irradiation. It was found that high-LET radiation would be more likely than low-LET radiation to induce additional DSBs within the HPRT gene if this gene already contained one DSB.

  9. TH-A-9A-01: Active Optical Flow Model: Predicting Voxel-Level Dose Prediction in Spine SBRT

    SciTech Connect

    Liu, J; Wu, Q.J.; Yin, F; Kirkpatrick, J; Cabrera, A; Ge, Y

    2014-06-15

    Purpose: To predict voxel-level dose distribution and enable effective evaluation of cord dose sparing in spine SBRT. Methods: We present an active optical flow model (AOFM) to statistically describe cord dose variations and train a predictive model to represent correlations between AOFM and PTV contours. Thirty clinically accepted spine SBRT plans are evenly divided into training and testing datasets. The development of predictive model consists of 1) collecting a sequence of dose maps including PTV and OAR (spinal cord) as well as a set of associated PTV contours adjacent to OAR from the training dataset, 2) classifying data into five groups based on PTV's locations relative to OAR, two “Top”s, “Left”, “Right”, and “Bottom”, 3) randomly selecting a dose map as the reference in each group and applying rigid registration and optical flow deformation to match all other maps to the reference, 4) building AOFM by importing optical flow vectors and dose values into the principal component analysis (PCA), 5) applying another PCA to features of PTV and OAR contours to generate an active shape model (ASM), and 6) computing a linear regression model of correlations between AOFM and ASM.When predicting dose distribution of a new case in the testing dataset, the PTV is first assigned to a group based on its contour characteristics. Contour features are then transformed into ASM's principal coordinates of the selected group. Finally, voxel-level dose distribution is determined by mapping from the ASM space to the AOFM space using the predictive model. Results: The DVHs predicted by the AOFM-based model and those in clinical plans are comparable in training and testing datasets. At 2% volume the dose difference between predicted and clinical plans is 4.2±4.4% and 3.3±3.5% in the training and testing datasets, respectively. Conclusion: The AOFM is effective in predicting voxel-level dose distribution for spine SBRT. Partially supported by NIH/NCI under grant

  10. Imprecision in predicted dose from /sup 137/Cs resulting from biological variability

    SciTech Connect

    Dunning, D.E. Jr.; Schwarz, G.

    1981-01-01

    The variability of observed values of human metabolic and physiological characteristics which influence estimates of dose from ingestion of a unit of Cesium-137 activity, and the subsequent predicted total-body dose commitment is analyzed. The analysis is based on extensive literature review and statistical comparison of parameter variability, correlation and reliability. (PSB)

  11. NEUTRON GENERATOR FACILITY AT SFU: GEANT4 DOSE RATE PREDICTION AND VERIFICATION.

    PubMed

    Williams, J; Chester, A; Domingo, T; Rizwan, U; Starosta, K; Voss, P

    2016-11-01

    Detailed dose rate maps for a neutron generator facility at Simon Fraser University were produced via the GEANT4 Monte Carlo framework. Predicted neutron dose rates throughout the facility were compared with radiation survey measurements made during the facility commissioning process. When accounting for thermal neutrons, the prediction and measurement agree within a factor of 2 or better in most survey locations, and within 10 % inside the vault housing the neutron generator.

  12. Voxel-based dose prediction with multi-patient atlas selection for automated radiotherapy treatment planning

    NASA Astrophysics Data System (ADS)

    McIntosh, Chris; Purdie, Thomas G.

    2017-01-01

    Automating the radiotherapy treatment planning process is a technically challenging problem. The majority of automated approaches have focused on customizing and inferring dose volume objectives to be used in plan optimization. In this work we outline a multi-patient atlas-based dose prediction approach that learns to predict the dose-per-voxel for a novel patient directly from the computed tomography planning scan without the requirement of specifying any objectives. Our method learns to automatically select the most effective atlases for a novel patient, and then map the dose from those atlases onto the novel patient. We extend our previous work to include a conditional random field for the optimization of a joint distribution prior that matches the complementary goals of an accurately spatially distributed dose distribution while still adhering to the desired dose volume histograms. The resulting distribution can then be used for inverse-planning with a new spatial dose objective, or to create typical dose volume objectives for the canonical optimization pipeline. We investigated six treatment sites (633 patients for training and 113 patients for testing) and evaluated the mean absolute difference in all DVHs for the clinical and predicted dose distribution. The results on average are favorable in comparison to our previous approach (1.91 versus 2.57). Comparing our method with and without atlas-selection further validates that atlas-selection improved dose prediction on average in whole breast (0.64 versus 1.59), prostate (2.13 versus 4.07), and rectum (1.46 versus 3.29) while it is less important in breast cavity (0.79 versus 0.92) and lung (1.33 versus 1.27) for which there is high conformity and minimal dose shaping. In CNS brain, atlas-selection has the potential to be impactful (3.65 versus 5.09), but selecting the ideal atlas is the most challenging.

  13. Knowledge-based prediction of three-dimensional dose distributions for external beam radiotherapy

    SciTech Connect

    Shiraishi, Satomi; Moore, Kevin L.

    2016-01-15

    Purpose: To demonstrate knowledge-based 3D dose prediction for external beam radiotherapy. Methods: Using previously treated plans as training data, an artificial neural network (ANN) was trained to predict a dose matrix based on patient-specific geometric and planning parameters, such as the closest distance (r) to planning target volume (PTV) and organ-at-risks (OARs). Twenty-three prostate and 43 stereotactic radiosurgery/radiotherapy (SRS/SRT) cases with at least one nearby OAR were studied. All were planned with volumetric-modulated arc therapy to prescription doses of 81 Gy for prostate and 12–30 Gy for SRS. Using these clinically approved plans, ANNs were trained to predict dose matrix and the predictive accuracy was evaluated using the dose difference between the clinical plan and prediction, δD = D{sub clin} − D{sub pred}. The mean (〈δD{sub r}〉), standard deviation (σ{sub δD{sub r}}), and their interquartile range (IQR) for the training plans were evaluated at a 2–3 mm interval from the PTV boundary (r{sub PTV}) to assess prediction bias and precision. Initially, unfiltered models which were trained using all plans in the cohorts were created for each treatment site. The models predict approximately the average quality of OAR sparing. Emphasizing a subset of plans that exhibited superior to the average OAR sparing during training, refined models were created to predict high-quality rectum sparing for prostate and brainstem sparing for SRS. Using the refined model, potentially suboptimal plans were identified where the model predicted further sparing of the OARs was achievable. Replans were performed to test if the OAR sparing could be improved as predicted by the model. Results: The refined models demonstrated highly accurate dose distribution prediction. For prostate cases, the average prediction bias for all voxels irrespective of organ delineation ranged from −1% to 0% with maximum IQR of 3% over r{sub PTV} ∈ [ − 6, 30] mm. The

  14. Contextual Atlas Regression Forests: Multiple-Atlas-Based Automated Dose Prediction in Radiation Therapy.

    PubMed

    McIntosh, Chris; Purdie, Thomas G

    2016-04-01

    Radiation therapy is an integral part of cancer treatment, but to date it remains highly manual. Plans are created through optimization of dose volume objectives that specify intent to minimize, maximize, or achieve a prescribed dose level to clinical targets and organs. Optimization is NP-hard, requiring highly iterative and manual initialization procedures. We present a proof-of-concept for a method to automatically infer the radiation dose directly from the patient's treatment planning image based on a database of previous patients with corresponding clinical treatment plans. Our method uses regression forests augmented with density estimation over the most informative features to learn an automatic atlas-selection metric that is tailored to dose prediction. We validate our approach on 276 patients from 3 clinical treatment plan sites (whole breast, breast cavity, and prostate), with an overall dose prediction accuracies of 78.68%, 64.76%, 86.83% under the Gamma metric.

  15. Can radiation therapy treatment planning system accurately predict surface doses in postmastectomy radiation therapy patients?

    SciTech Connect

    Wong, Sharon; Back, Michael; Tan, Poh Wee; Lee, Khai Mun; Baggarley, Shaun; Lu, Jaide Jay

    2012-07-01

    Skin doses have been an important factor in the dose prescription for breast radiotherapy. Recent advances in radiotherapy treatment techniques, such as intensity-modulated radiation therapy (IMRT) and new treatment schemes such as hypofractionated breast therapy have made the precise determination of the surface dose necessary. Detailed information of the dose at various depths of the skin is also critical in designing new treatment strategies. The purpose of this work was to assess the accuracy of surface dose calculation by a clinically used treatment planning system and those measured by thermoluminescence dosimeters (TLDs) in a customized chest wall phantom. This study involved the construction of a chest wall phantom for skin dose assessment. Seven TLDs were distributed throughout each right chest wall phantom to give adequate representation of measured radiation doses. Point doses from the CMS Xio Registered-Sign treatment planning system (TPS) were calculated for each relevant TLD positions and results correlated. There were no significant difference between measured absorbed dose by TLD and calculated doses by the TPS (p > 0.05 (1-tailed). Dose accuracy of up to 2.21% was found. The deviations from the calculated absorbed doses were overall larger (3.4%) when wedges and bolus were used. 3D radiotherapy TPS is a useful and accurate tool to assess the accuracy of surface dose. Our studies have shown that radiation treatment accuracy expressed as a comparison between calculated doses (by TPS) and measured doses (by TLD dosimetry) can be accurately predicted for tangential treatment of the chest wall after mastectomy.

  16. A Comparison of Dose Metrics to Predict Local Tumor Control for Photofrin-mediated Photodynamic Therapy.

    PubMed

    Qiu, Haixia; Kim, Michele M; Penjweini, Rozhin; Finlay, Jarod C; Busch, Theresa M; Wang, Tianhao; Guo, Wensheng; Cengel, Keith A; Simone, Charles B; Glatstein, Eli; Zhu, Timothy C

    2017-01-13

    This preclinical study examines light fluence, photodynamic therapy (PDT) dose and "apparent reacted singlet oxygen," [(1) O2 ]rx , to predict local control rate (LCR) for Photofrin-mediated PDT of radiation-induced fibrosarcoma (RIF) tumors. Mice bearing RIF tumors were treated with in-air fluences (50-250 J cm(-2) ) and in-air fluence rates (50-150 mW cm(-2) ) at Photofrin dosages of 5 and 15 mg kg(-1) and a drug-light interval of 24 h using a 630-nm, 1-cm-diameter collimated laser. A macroscopic model was used to calculate [(1) O2 ]rx and PDT dose based on in vivo explicit dosimetry of the drug concentration, light fluence and tissue optical properties. PDT dose and [(1) O2 ]rx were defined as a temporal integral of drug concentration and fluence rate, and singlet oxygen concentration consumed divided by the singlet oxygen lifetime, respectively. LCR was stratified for different dose metrics for 74 mice (66 + 8 control). Complete tumor control at 14 days was observed for [(1) O2 ]rx ≥ 1.1 mm or PDT dose ≥1200 μm J cm(-2) but cannot be predicted with fluence alone. LCR increases with increasing [(1) O2 ]rx and PDT dose but is not well correlated with fluence. Comparing dosimetric quantities, [(1) O2 ]rx outperformed both PDT dose and fluence in predicting tumor response and correlating with LCR.

  17. SU-E-T-196: Comparative Analysis of Surface Dose Measurements Using MOSFET Detector and Dose Predicted by Eclipse - AAA with Varying Dose Calculation Grid Size

    SciTech Connect

    Badkul, R; Nejaiman, S; Pokhrel, D; Jiang, H; Kumar, P

    2015-06-15

    Purpose: Skin dose can be the limiting factor and fairly common reason to interrupt the treatment, especially for treating head-and-neck with Intensity-modulated-radiation-therapy(IMRT) or Volumetrically-modulated - arc-therapy (VMAT) and breast with tangentially-directed-beams. Aim of this study was to investigate accuracy of near-surface dose predicted by Eclipse treatment-planning-system (TPS) using Anisotropic-Analytic Algorithm (AAA)with varying calculation grid-size and comparing with metal-oxide-semiconductor-field-effect-transistors(MOSFETs)measurements for a range of clinical-conditions (open-field,dynamic-wedge, physical-wedge, IMRT,VMAT). Methods: QUASAR™-Body-Phantom was used in this study with oval curved-surfaces to mimic breast, chest wall and head-and-neck sites.A CT-scan was obtained with five radio-opaque markers(ROM) placed on the surface of phantom to mimic the range of incident angles for measurements and dose prediction using 2mm slice thickness.At each ROM, small structure(1mmx2mm) were contoured to obtain mean-doses from TPS.Calculations were performed for open-field,dynamic-wedge,physical-wedge,IMRT and VMAT using Varian-21EX,6&15MV photons using twogrid-sizes:2.5mm and 1mm.Calibration checks were performed to ensure that MOSFETs response were within ±5%.Surface-doses were measured at five locations and compared with TPS calculations. Results: For 6MV: 2.5mm grid-size,mean calculated doses(MCD)were higher by 10%(±7.6),10%(±7.6),20%(±8.5),40%(±7.5),30%(±6.9) and for 1mm grid-size MCD were higher by 0%(±5.7),0%(±4.2),0%(±5.5),1.2%(±5.0),1.1% (±7.8) for open-field,dynamic-wedge,physical-wedge,IMRT,VMAT respectively.For 15MV: 2.5mm grid-size,MCD were higher by 30%(±14.6),30%(±14.6),30%(±14.0),40%(±11.0),30%(±3.5)and for 1mm grid-size MCD were higher by 10% (±10.6), 10%(±9.8),10%(±8.0),30%(±7.8),10%(±3.8) for open-field, dynamic-wedge, physical-wedge, IMRT, VMAT respectively.For 6MV, 86% and 56% of all measured values

  18. Novel Radiobiological Gamma Index for Evaluation of 3-Dimensional Predicted Dose Distribution

    SciTech Connect

    Sumida, Iori; Yamaguchi, Hajime; Kizaki, Hisao; Aboshi, Keiko; Tsujii, Mari; Yoshikawa, Nobuhiko; Yamada, Yuji; Suzuki, Osamu; Seo, Yuji; Isohashi, Fumiaki; Yoshioka, Yasuo; Ogawa, Kazuhiko

    2015-07-15

    Purpose: To propose a gamma index-based dose evaluation index that integrates the radiobiological parameters of tumor control (TCP) and normal tissue complication probabilities (NTCP). Methods and Materials: Fifteen prostate and head and neck (H&N) cancer patients received intensity modulated radiation therapy. Before treatment, patient-specific quality assurance was conducted via beam-by-beam analysis, and beam-specific dose error distributions were generated. The predicted 3-dimensional (3D) dose distribution was calculated by back-projection of relative dose error distribution per beam. A 3D gamma analysis of different organs (prostate: clinical [CTV] and planned target volumes [PTV], rectum, bladder, femoral heads; H&N: gross tumor volume [GTV], CTV, spinal cord, brain stem, both parotids) was performed using predicted and planned dose distributions under 2%/2 mm tolerance and physical gamma passing rate was calculated. TCP and NTCP values were calculated for voxels with physical gamma indices (PGI) >1. We propose a new radiobiological gamma index (RGI) to quantify the radiobiological effects of TCP and NTCP and calculate radiobiological gamma passing rates. Results: The mean RGI gamma passing rates for prostate cases were significantly different compared with those of PGI (P<.03–.001). The mean RGI gamma passing rates for H&N cases (except for GTV) were significantly different compared with those of PGI (P<.001). Differences in gamma passing rates between PGI and RGI were due to dose differences between the planned and predicted dose distributions. Radiobiological gamma distribution was visualized to identify areas where the dose was radiobiologically important. Conclusions: RGI was proposed to integrate radiobiological effects into PGI. This index would assist physicians and medical physicists not only in physical evaluations of treatment delivery accuracy, but also in clinical evaluations of predicted dose distribution.

  19. Use of dose-dependent absorption into target tissues to more accurately predict cancer risk at low oral doses of hexavalent chromium.

    PubMed

    Haney, J

    2015-02-01

    The mouse dose at the lowest water concentration used in the National Toxicology Program hexavalent chromium (CrVI) drinking water study (NTP, 2008) is about 74,500 times higher than the approximate human dose corresponding to the 35-city geometric mean reported in EWG (2010) and over 1000 times higher than that based on the highest reported tap water concentration. With experimental and environmental doses differing greatly, it is a regulatory challenge to extrapolate high-dose results to environmental doses orders of magnitude lower in a meaningful and toxicologically predictive manner. This seems particularly true for the low-dose extrapolation of results for oral CrVI-induced carcinogenesis since dose-dependent differences in the dose fraction absorbed by mouse target tissues are apparent (Kirman et al., 2012). These data can be used for a straightforward adjustment of the USEPA (2010) draft oral slope factor (SFo) to be more predictive of risk at environmentally-relevant doses. More specifically, the evaluation of observed and modeled differences in the fraction of dose absorbed by target tissues at the point-of-departure for the draft SFo calculation versus lower doses suggests that the draft SFo be divided by a dose-specific adjustment factor of at least an order of magnitude to be less over-predictive of risk at more environmentally-relevant doses.

  20. MO-FG-303-03: Demonstration of Universal Knowledge-Based 3D Dose Prediction

    SciTech Connect

    Shiraishi, S; Moore, K L

    2015-06-15

    Purpose: To demonstrate a knowledge-based 3D dose prediction methodology that can accurately predict achievable radiotherapy distributions. Methods: Using previously treated plans as input, an artificial neural network (ANN) was trained to predict 3D dose distributions based on 14 patient-specific anatomical parameters including the distance (r) to planning target volume (PTV) boundary, organ-at-risk (OAR) boundary distances, and angular position ( θ,φ). 23 prostate and 49 stereotactic radiosurgery (SRS) cases with ≥1 nearby OARs were studied. All were planned with volumetric-modulated arc therapy (VMAT) to prescription doses of 81Gy for prostate and 12–30Gy for SRS. Site-specific ANNs were trained using all prostate 23 plans and using a 24 randomly-selected subset for the SRS model. The remaining 25 SRS plans were used to validate the model. To quantify predictive accuracy, the dose difference between the clinical plan and prediction were calculated on a voxel-by-voxel basis δD(r,θ,φ)=Dclin(r,θ,φ)-Dpred(r, θ,φ). Grouping voxels by boundary distance, the mean <δ Dr>=(1/N)Σ -θ,φ D(r,θ,φ) and inter-quartile range (IQR) quantified the accuracy of this method for deriving DVH estimations. The standard deviation (σ) of δ D quantified the 3D dose prediction error on a voxel-by-voxel basis. Results: The ANNs were highly accurate in predictive ability for both prostate and SRS plans. For prostate, <δDr> ranged from −0.8% to +0.6% (max IQR=3.8%) over r=0–32mm, while 3D dose prediction accuracy averaged from σ=5–8% across the same range. For SRS, from r=0–34mm the training set <δDr> ranged from −3.7% to +1.5% (max IQR=4.4%) while the validation set <δDr> ranged from −2.2% to +5.8% (max IQR=5.3%). 3D dose prediction accuracy averaged σ=2.5% for the training set and σ=4.0% over the same interval. Conclusion: The study demonstrates this technique’s ability to predict achievable 3D dose distributions for VMAT SRS and prostate. Future

  1. Radiation Dose Predicts for Biochemical Control in Intermediate-Risk Prostate Cancer Patients Treated With Low-Dose-Rate Brachytherapy

    SciTech Connect

    Ho, Alice Y.; Burri, Ryan J.; Cesaretti, Jamie A.; Stone, Nelson N.; Stock, Richard G.

    2009-09-01

    Purpose: To evaluate the influence of patient- and treatment-related factors on freedom from biochemical failure (FFbF) in patients with intermediate-risk prostate cancer. Methods and Materials: From a prospectively collected database of 2250 men treated at Mount Sinai Hospital from 1990 to 2004 with low-dose-rate brachytherapy for prostate cancer, 558 men with either one or more intermediate-risk features (prostate-specific antigen [PSA] level 10-20 ng/mL, Gleason score 7, or Stage T2b) were identified who had a minimum follow-up of 24 months and postimplant CT-based dosimetric analysis. Biologically effective dose (BED) values were calculated to compare doses from different isotopes and treatment regimens. Patients were treated with brachytherapy with or without hormone therapy and/or external-beam radiotherapy. Patient- and treatment-related factors were analyzed with respect to FFbF. The median follow-up was 60 months (range, 24-167 months). Biochemical failure was defined according to the Phoenix definition. Univariate analyses were used to determine whether any variable was predictive of FFbF. A two-sided p value of <0.05 was considered significant. Results: Overall, the actuarial FFbF at 10 years was 86%. Dose (BED <150 Gy{sub 2} vs. {>=}150 Gy{sub 2}) was the only significant predictor of FFbF (p < 0.001). None of the other variables (PSA, external-beam radiotherapy, Gleason score, treatment type, hormones, stage, and number of risk factors) was found to be a statistically significant predictor of 10-year FFbF. Conclusions: Radiation dose is an important predictor of FFbF in intermediate-risk prostate cancer. Treatment should continue to be individualized according to presenting disease characteristics until results from Radiation Therapy Oncology Group trial 0232 become available.

  2. Prediction of multidimensional drug dose responses based on measurements of drug pairs

    PubMed Central

    Zimmer, Anat; Katzir, Itay; Dekel, Erez; Alon, Uri

    2016-01-01

    Finding potent multidrug combinations against cancer and infections is a pressing therapeutic challenge; however, screening all combinations is difficult because the number of experiments grows exponentially with the number of drugs and doses. To address this, we present a mathematical model that predicts the effects of three or more antibiotics or anticancer drugs at all doses based only on measurements of drug pairs at a few doses, without need for mechanistic information. The model provides accurate predictions on available data for antibiotic combinations, and on experiments presented here on the response matrix of three cancer drugs at eight doses per drug. This approach offers a way to search for effective multidrug combinations using a small number of experiments. PMID:27562164

  3. Prediction of multidimensional drug dose responses based on measurements of drug pairs.

    PubMed

    Zimmer, Anat; Katzir, Itay; Dekel, Erez; Mayo, Avraham E; Alon, Uri

    2016-09-13

    Finding potent multidrug combinations against cancer and infections is a pressing therapeutic challenge; however, screening all combinations is difficult because the number of experiments grows exponentially with the number of drugs and doses. To address this, we present a mathematical model that predicts the effects of three or more antibiotics or anticancer drugs at all doses based only on measurements of drug pairs at a few doses, without need for mechanistic information. The model provides accurate predictions on available data for antibiotic combinations, and on experiments presented here on the response matrix of three cancer drugs at eight doses per drug. This approach offers a way to search for effective multidrug combinations using a small number of experiments.

  4. Estimation of Maximum Recommended Therapeutic Dose Using Predicted Promiscuity and Potency

    PubMed Central

    Liu, T; Oprea, T; Ursu, O; Hasselgren, C

    2016-01-01

    We report a simple model that predicts the maximum recommended therapeutic dose (MRTD) of small molecule drugs based on an assessment of likely protein–drug interactions. Previously, we reported methods for computational estimation of drug promiscuity and potency. We used these concepts to build a linear model derived from 238 small molecular drugs to predict MRTD. We applied this model successfully to predict MRTDs for 16 nonsteroidal antiinflammatory drugs (NSAIDs) and 14 antiretroviral drugs. Of note, based on the estimated promiscuity of low‐dose drugs (and active chemicals), we identified 83 proteins as “high‐risk off‐targets” (HROTs) that are often associated with low doses; the evaluation of interactions with HROTs may be useful during early phases of drug discovery. Our model helps explain the MRTD for drugs with severe adverse reactions caused by interactions with HROTs. PMID:27736015

  5. Incorporation of gantry angle correction for 3D dose prediction in intensity-modulated radiation therapy

    PubMed Central

    Sumida, Iori; Yamaguchi, Hajime; Kizaki, Hisao; Aboshi, Keiko; Tsujii, Mari; Yamada, Yuji; Yagi, Masashi; Ogawa, Kazuhiko

    2015-01-01

    Pretreatment dose verification with beam-by-beam analysis for intensity-modulated radiation therapy (IMRT) is commonly performed with a gantry angle of 0° using a 2D diode detector array. Any changes in multileaf collimator (MLC) position between the actual treatment gantry angle and 0° may result in deviations from the planned dose. We evaluated the effects of MLC positioning errors between the actual treatment gantry angles and nominal gantry angles. A gantry angle correction (GAC) factor was generated by performing a non-gap test at various gantry angles using an electronic portal imaging device (EPID). To convert pixel intensity to dose at the MLC abutment positions, a non-gap test was performed using an EPID and a film at 0° gantry angle. We then assessed the correlations between pixel intensities and doses. Beam-by-beam analyses for 15 prostate IMRT cases as patient-specific quality assurance were performed with a 2D diode detector array at 0° gantry angle to determine the relative dose error for each beam. The resulting relative dose error with or without GAC was added back to the original dose grid for each beam. We compared the predicted dose distributions with or without GAC for film measurements to validate GAC effects. A gamma pass rate with a tolerance of 2%/2 mm was used to evaluate these dose distributions. The gamma pass rate with GAC was higher than that without GAC (P = 0.01). The predicted dose distribution improved with GAC, although the dosimetric effect to a patient was minimal. PMID:25742866

  6. Incorporation of gantry angle correction for 3D dose prediction in intensity-modulated radiation therapy.

    PubMed

    Sumida, Iori; Yamaguchi, Hajime; Kizaki, Hisao; Aboshi, Keiko; Tsujii, Mari; Yamada, Yuji; Yagi, Masashi; Ogawa, Kazuhiko

    2015-05-01

    Pretreatment dose verification with beam-by-beam analysis for intensity-modulated radiation therapy (IMRT) is commonly performed with a gantry angle of 0° using a 2D diode detector array. Any changes in multileaf collimator (MLC) position between the actual treatment gantry angle and 0° may result in deviations from the planned dose. We evaluated the effects of MLC positioning errors between the actual treatment gantry angles and nominal gantry angles. A gantry angle correction (GAC) factor was generated by performing a non-gap test at various gantry angles using an electronic portal imaging device (EPID). To convert pixel intensity to dose at the MLC abutment positions, a non-gap test was performed using an EPID and a film at 0° gantry angle. We then assessed the correlations between pixel intensities and doses. Beam-by-beam analyses for 15 prostate IMRT cases as patient-specific quality assurance were performed with a 2D diode detector array at 0° gantry angle to determine the relative dose error for each beam. The resulting relative dose error with or without GAC was added back to the original dose grid for each beam. We compared the predicted dose distributions with or without GAC for film measurements to validate GAC effects. A gamma pass rate with a tolerance of 2%/2 mm was used to evaluate these dose distributions. The gamma pass rate with GAC was higher than that without GAC (P = 0.01). The predicted dose distribution improved with GAC, although the dosimetric effect to a patient was minimal.

  7. MO-G-304-02: Knowledge Based DVH Prediction Using a Geometric Dose Transform

    SciTech Connect

    Staub, D; Wang, J; Jiang, S

    2015-06-15

    Purpose: To demonstrate a novel method for predicting patient dose-volume histograms (DVHs) using a prior database of optimized radiotherapy treatment plans. Such predicted DVHs could be useful for automating treatment planning. Methods: Our initial demonstration utilized a database of 100 prostate intensity-modulated radiotherapy (IMRT) data-sets. Each data-set contained a CT image with contours of the planning target volume (PTV), rectum, and bladder, the parameters of a clinically approved IMRT plan, and a corresponding simulated dose distribution. We applied a novel geometric transformation to remove the influence of the PTV size, shape, and location on the dose distribution. We termed the transformed distribution the geometrically normalized dose distribution (GNDD). This normalization transform was applied to 80 data-sets randomly selected from the database, and a population GNDD was computed as the average. Next, the population GNDD was mapped onto each of the remaining 20 patient datasets using the reverse of the geometric normalization transform, and predicted DVHs were calculated from the reverse transformed dose distributions (GNDD-DVHs). In addition, a state of the art machine learning based method from the literature was tested for comparison. Results: DVH prediction accuracy was quantified by calculating the relative root mean squared error (rRMSE) on predicted DVHs for the 20 test patients using their known DVHs. For bladder, rectum, and PTV average rRMSEs for the GNDD method were 9.7 ± 4.2%, 13.9 ± 6.0%, and 2.3 ± 0.5% respectively. Prediction results using GNDD were roughly equivalent to that from the machine learning method. Conclusion: We developed a new method for predicting DVH curves from a database of prior patient plans. We demonstrated that our simple approach achieves accuracy comparable to a method using a complicated machine learning based approach.

  8. Improving the Accuracy of a Heliocentric Potential (HCP) Prediction Model for the Aviation Radiation Dose

    NASA Astrophysics Data System (ADS)

    Hwang, Junga; Yoon, Kyoung-Won; Jo, Gyeongbok; Noh, Sung-Jun

    2016-12-01

    The space radiation dose over air routes including polar routes should be carefully considered, especially when space weather shows sudden disturbances such as coronal mass ejections (CMEs), flares, and accompanying solar energetic particle events. We recently established a heliocentric potential (HCP) prediction model for real-time operation of the CARI-6 and CARI-6M programs. Specifically, the HCP value is used as a critical input value in the CARI-6/6M programs, which estimate the aviation route dose based on the effective dose rate. The CARI-6/6M approach is the most widely used technique, and the programs can be obtained from the U.S. Federal Aviation Administration (FAA). However, HCP values are given at a one month delay on the FAA official webpage, which makes it difficult to obtain real-time information on the aviation route dose. In order to overcome this critical limitation regarding the time delay for space weather customers, we developed a HCP prediction model based on sunspot number variations (Hwang et al. 2015). In this paper, we focus on improvements to our HCP prediction model and update it with neutron monitoring data. We found that the most accurate method to derive the HCP value involves (1) real-time daily sunspot assessments, (2) predictions of the daily HCP by our prediction algorithm, and (3) calculations of the resultant daily effective dose rate. Additionally, we also derived the HCP prediction algorithm in this paper by using ground neutron counts. With the compensation stemming from the use of ground neutron count data, the newly developed HCP prediction model was improved.

  9. Predicting astronaut radiation doses from major solar particle events using artificial intelligence

    NASA Astrophysics Data System (ADS)

    Tehrani, Nazila H.

    1998-06-01

    Space radiation is an important issue for manned space flight. For long missions outside of the Earth's magnetosphere, there are two major sources of exposure. Large Solar Particle Events (SPEs) consisting of numerous energetic protons and other heavy ions emitted by the Sun, and the Galactic Cosmic Rays (GCRs) that constitute an isotropic radiation field of low flux and high energy. In deep-space missions both SPEs and GCRs can be hazardous to the space crew. SPEs can provide an acute dose, which is a large dose over a short period of time. The acute doses from a large SPE that could be received by an astronaut with shielding as thick as a spacesuit maybe as large as 500 cGy. GCRs will not provide acute doses, but may increase the lifetime risk of cancer from prolonged exposures in a range of 40-50 cSv/yr. In this research, we are using artificial intelligence to model the dose-time profiles during a major solar particle event. Artificial neural networks are reliable approximators for nonlinear functions. In this study we design a dynamic network. This network has the ability to update its dose predictions as new input dose data is received while the event is occurring. To accomplish this temporal behavior of the system we use an innovative Sliding Time-Delay Neural Network (STDNN). By using a STDNN one can predict doses received from large SPEs while the event is happening. The parametric fits and actual calculated doses for the skin, eye and bone marrow are used. The parametric data set obtained by fitting the Weibull functional forms to the calculated dose points has been divided into two subsets. The STDNN has been trained using some of these parametric events. The other subset of parametric data and the actual doses are used for testing with the resulting weights and biases of the first set. This is done to show that the network can generalize. Results of this testing indicate that the STDNN is capable of predicting doses from events that it has not seen

  10. Predicting standard-dose PET image from low-dose PET and multimodal MR images using mapping-based sparse representation

    NASA Astrophysics Data System (ADS)

    Wang, Yan; Zhang, Pei; An, Le; Ma, Guangkai; Kang, Jiayin; Shi, Feng; Wu, Xi; Zhou, Jiliu; Lalush, David S.; Lin, Weili; Shen, Dinggang

    2016-01-01

    Positron emission tomography (PET) has been widely used in clinical diagnosis for diseases and disorders. To obtain high-quality PET images requires a standard-dose radionuclide (tracer) injection into the human body, which inevitably increases risk of radiation exposure. One possible solution to this problem is to predict the standard-dose PET image from its low-dose counterpart and its corresponding multimodal magnetic resonance (MR) images. Inspired by the success of patch-based sparse representation (SR) in super-resolution image reconstruction, we propose a mapping-based SR (m-SR) framework for standard-dose PET image prediction. Compared with the conventional patch-based SR, our method uses a mapping strategy to ensure that the sparse coefficients, estimated from the multimodal MR images and low-dose PET image, can be applied directly to the prediction of standard-dose PET image. As the mapping between multimodal MR images (or low-dose PET image) and standard-dose PET images can be particularly complex, one step of mapping is often insufficient. To this end, an incremental refinement framework is therefore proposed. Specifically, the predicted standard-dose PET image is further mapped to the target standard-dose PET image, and then the SR is performed again to predict a new standard-dose PET image. This procedure can be repeated for prediction refinement of the iterations. Also, a patch selection based dictionary construction method is further used to speed up the prediction process. The proposed method is validated on a human brain dataset. The experimental results show that our method can outperform benchmark methods in both qualitative and quantitative measures.

  11. Prediction of standard-dose brain PET image by using MRI and low-dose brain [{sup 18}F]FDG PET images

    SciTech Connect

    Kang, Jiayin; Gao, Yaozong; Shi, Feng; Lalush, David S.; Lin, Weili; Shen, Dinggang

    2015-09-15

    Purpose: Positron emission tomography (PET) is a nuclear medical imaging technology that produces 3D images reflecting tissue metabolic activity in human body. PET has been widely used in various clinical applications, such as in diagnosis of brain disorders. High-quality PET images play an essential role in diagnosing brain diseases/disorders. In practice, in order to obtain high-quality PET images, a standard-dose radionuclide (tracer) needs to be used and injected into a living body. As a result, it will inevitably increase the patient’s exposure to radiation. One solution to solve this problem is predicting standard-dose PET images using low-dose PET images. As yet, no previous studies with this approach have been reported. Accordingly, in this paper, the authors propose a regression forest based framework for predicting a standard-dose brain [{sup 18}F]FDG PET image by using a low-dose brain [{sup 18}F]FDG PET image and its corresponding magnetic resonance imaging (MRI) image. Methods: The authors employ a regression forest for predicting the standard-dose brain [{sup 18}F]FDG PET image by low-dose brain [{sup 18}F]FDG PET and MRI images. Specifically, the proposed method consists of two main steps. First, based on the segmented brain tissues (i.e., cerebrospinal fluid, gray matter, and white matter) in the MRI image, the authors extract features for each patch in the brain image from both low-dose PET and MRI images to build tissue-specific models that can be used to initially predict standard-dose brain [{sup 18}F]FDG PET images. Second, an iterative refinement strategy, via estimating the predicted image difference, is used to further improve the prediction accuracy. Results: The authors evaluated their algorithm on a brain dataset, consisting of 11 subjects with MRI, low-dose PET, and standard-dose PET images, using leave-one-out cross-validations. The proposed algorithm gives promising results with well-estimated standard-dose brain [{sup 18}F]FDG PET

  12. Using dose-surface maps to predict radiation-induced rectal bleeding: a neural network approach

    NASA Astrophysics Data System (ADS)

    Buettner, Florian; Gulliford, Sarah L.; Webb, Steve; Partridge, Mike

    2009-09-01

    The incidence of late-toxicities after radiotherapy can be modelled based on the dose delivered to the organ under consideration. Most predictive models reduce the dose distribution to a set of dose-volume parameters and do not take the spatial distribution of the dose into account. The aim of this study was to develop a classifier predicting radiation-induced rectal bleeding using all available information on the dose to the rectal wall. The dose was projected on a two-dimensional dose-surface map (DSM) by virtual rectum-unfolding. These DSMs were used as inputs for a classification method based on locally connected neural networks. In contrast to fully connected conventional neural nets, locally connected nets take the topology of the input into account. In order to train the nets, data from 329 patients from the RT01 trial (ISRCTN 47772397) were split into ten roughly equal parts. By using nine of these parts as a training set and the remaining part as an independent test set, a ten-fold cross-validation was performed. Ensemble learning was used and 250 nets were built from randomly selected patients from the training set. Out of these 250 nets, an ensemble of expert nets was chosen. The performances of the full ensemble and of the expert ensemble were quantified by using receiver-operator-characteristic (ROC) curves. In order to quantify the predictive power of the shape, ensembles of fully connected conventional neural nets based on dose-surface histograms (DSHs) were generated and their performances were quantified. The expert ensembles performed better than or equally as well as the full ensembles. The area under the ROC curve for the DSM-based expert ensemble was 0.64. The area under the ROC curve for the DSH-based expert ensemble equalled 0.59. This difference in performance indicates that not only volumetric, but also morphological aspects of the dose distribution are correlated to rectal bleeding after radiotherapy. Thus, the shape of the dose

  13. Tumor-Absorbed Dose Predicts Progression-Free Survival Following 131I-Tositumomab Radioimmunotherapy

    PubMed Central

    Dewaraja, Yuni K.; Schipper, Matthew J.; Shen, Jincheng; Smith, Lauren B.; Murgic, Jure; Savas, Hatice; Youssef, Ehab; Regan, Denise; Wilderman, Scott J.; Roberson, Peter L.; Kaminski, Mark S.; Avram, Anca M.

    2014-01-01

    The study aimed at identifying patient-specific dosimetric and nondosimetric factors predicting outcome of non-Hodgkin lymphoma patients after 131I-tositumomab radioimmunotherapy for potential use in treatment planning. Methods Tumor-absorbed dose measures were estimated for 130 tumors in 39 relapsed or refractory non-Hodgkin lymphoma patients by coupling SPECT/CT imaging with the Dose Planning Method (DPM) Monte Carlo code. Equivalent biologic effect was calculated to assess the biologic effects of nonuniform absorbed dose including the effects of the unlabeled antibody. Evaluated nondosimetric covariates included histology, presence of bulky disease, and prior treatment history. Tumor level outcome was based on volume shrinkage assessed on follow-up CT. Patient level outcome measures were overall response (OR), complete response (CR), and progression-free survival (PFS), determined from clinical assessments that included PET/CT. Results The estimated mean tumor-absorbed dose had a median value of 275 cGy (range, 94–711 cGy). A high correlation was observed between tracer-predicted and therapy-delivered mean tumor-absorbed doses (P < 0.001; r = 0.85). In univariate tumor-level analysis, tumor shrinkage correlated significantly with almost all of the evaluated dosimetric factors, including equivalent biologic effect. Regression analysis showed that OR, CR, and PFS were associated with the dosimetric factors and equivalent biologic effect. Both mean tumor-absorbed dose (P = 0.025) and equivalent biologic effect (P = 0.035) were significant predictors of PFS whereas none of the nondosimetric covariates were found to be statistically significant factors affecting PFS. The most important finding of the study was that in Kaplan–Meier curves stratified by mean dose, longer PFS was observed in patients receiving mean tumor-absorbed doses greater than 200 cGy than in those receiving 200 cGy or less (median PFS, 13.6 vs. 1.9 mo for the 2 dose groups; log-rank P < 0

  14. Comparison of Risk Predicted by Multiple Norovirus Dose-Response Models and Implications for Quantitative Microbial Risk Assessment.

    PubMed

    Van Abel, Nicole; Schoen, Mary E; Kissel, John C; Meschke, J Scott

    2016-06-10

    The application of quantitative microbial risk assessments (QMRAs) to understand and mitigate risks associated with norovirus is increasingly common as there is a high frequency of outbreaks worldwide. A key component of QMRA is the dose-response analysis, which is the mathematical characterization of the association between dose and outcome. For Norovirus, multiple dose-response models are available that assume either a disaggregated or an aggregated intake dose. This work reviewed the dose-response models currently used in QMRA, and compared predicted risks from waterborne exposures (recreational and drinking) using all available dose-response models. The results found that the majority of published QMRAs of norovirus use the 1 F1 hypergeometric dose-response model with α = 0.04, β = 0.055. This dose-response model predicted relatively high risk estimates compared to other dose-response models for doses in the range of 1-1,000 genomic equivalent copies. The difference in predicted risk among dose-response models was largest for small doses, which has implications for drinking water QMRAs where the concentration of norovirus is low. Based on the review, a set of best practices was proposed to encourage the careful consideration and reporting of important assumptions in the selection and use of dose-response models in QMRA of norovirus. Finally, in the absence of one best norovirus dose-response model, multiple models should be used to provide a range of predicted outcomes for probability of infection.

  15. Prediction of in-phantom dose distribution using in-air neutron beam characteristics for BNCS

    SciTech Connect

    Verbeke, Jerome M.

    1999-12-14

    A monoenergetic neutron beam simulation study is carried out to determine the optimal neutron energy range for treatment of rheumatoid arthritis using radiation synovectomy. The goal of the treatment is the ablation of diseased synovial membranes in joints, such as knees and fingers. This study focuses on human knee joints. Two figures-of-merit are used to measure the neutron beam quality, the ratio of the synovium absorbed dose to the skin absorbed dose, and the ratio of the synovium absorbed dose to the bone absorbed dose. It was found that (a) thermal neutron beams are optimal for treatment, (b) similar absorbed dose rates and therapeutic ratios are obtained with monodirectional and isotropic neutron beams. Computation of the dose distribution in a human knee requires the simulation of particle transport from the neutron source to the knee phantom through the moderator. A method was developed to predict the dose distribution in a knee phantom from any neutron and photon beam spectra incident on the knee. This method was revealed to be reasonably accurate and enabled one to reduce by a factor of 10 the particle transport simulation time by modeling the moderator only.

  16. Per-beam, planar IMRT QA passing rates do not predict clinically relevant patient dose errors

    SciTech Connect

    Nelms, Benjamin E.; Zhen Heming; Tome, Wolfgang A.

    2011-02-15

    Purpose: The purpose of this work is to determine the statistical correlation between per-beam, planar IMRT QA passing rates and several clinically relevant, anatomy-based dose errors for per-patient IMRT QA. The intent is to assess the predictive power of a common conventional IMRT QA performance metric, the Gamma passing rate per beam. Methods: Ninety-six unique data sets were created by inducing four types of dose errors in 24 clinical head and neck IMRT plans, each planned with 6 MV Varian 120-leaf MLC linear accelerators using a commercial treatment planning system and step-and-shoot delivery. The error-free beams/plans were used as ''simulated measurements'' (for generating the IMRT QA dose planes and the anatomy dose metrics) to compare to the corresponding data calculated by the error-induced plans. The degree of the induced errors was tuned to mimic IMRT QA passing rates that are commonly achieved using conventional methods. Results: Analysis of clinical metrics (parotid mean doses, spinal cord max and D1cc, CTV D95, and larynx mean) vs IMRT QA Gamma analysis (3%/3 mm, 2/2, 1/1) showed that in all cases, there were only weak to moderate correlations (range of Pearson's r-values: -0.295 to 0.653). Moreover, the moderate correlations actually had positive Pearson's r-values (i.e., clinically relevant metric differences increased with increasing IMRT QA passing rate), indicating that some of the largest anatomy-based dose differences occurred in the cases of high IMRT QA passing rates, which may be called ''false negatives.'' The results also show numerous instances of false positives or cases where low IMRT QA passing rates do not imply large errors in anatomy dose metrics. In none of the cases was there correlation consistent with high predictive power of planar IMRT passing rates, i.e., in none of the cases did high IMRT QA Gamma passing rates predict low errors in anatomy dose metrics or vice versa. Conclusions: There is a lack of correlation between

  17. Clinical implementation of dose-volume histogram predictions for organs-at-risk in IMRT planning

    NASA Astrophysics Data System (ADS)

    Moore, K. L.; Appenzoller, L. M.; Tan, J.; Michalski, J. M.; Thorstad, W. L.; Mutic, S.

    2014-03-01

    True quality control (QC) of the planning process requires quantitative assessments of treatment plan quality itself, and QC in IMRT has been stymied by intra-patient anatomical variability and inherently complex three-dimensional dose distributions. In this work we describe the development of an automated system to reduce clinical IMRT planning variability and improve plan quality using mathematical models that predict achievable OAR DVHs based on individual patient anatomy. These models rely on the correlation of expected dose to the minimum distance from a voxel to the PTV surface, whereby a three-parameter probability distribution function (PDF) was used to model iso-distance OAR subvolume dose distributions. DVH models were obtained by fitting the evolution of the PDF with distance. Initial validation on clinical cohorts of 40 prostate and 24 head-and-neck plans demonstrated highly accurate model-based predictions for achievable DVHs in rectum, bladder, and parotid glands. By quantifying the integrated difference between candidate DVHs and predicted DVHs, the models correctly identified plans with under-spared OARs, validated by replanning all cases and correlating any realized improvements against the predicted gains. Clinical implementation of these predictive models was demonstrated in the PINNACLE treatment planning system by use of existing margin expansion utilities and the scripting functionality inherent to the system. To maintain independence from specific planning software, a system was developed in MATLAB to directly process DICOM-RT data. Both model training and patient-specific analyses were demonstrated with significant computational accelerations from parallelization.

  18. Effects of dose reduction on bone strength prediction using finite element analysis

    NASA Astrophysics Data System (ADS)

    Anitha, D.; Subburaj, Karupppasamy; Mei, Kai; Kopp, Felix K.; Foehr, Peter; Noel, Peter B.; Kirschke, Jan S.; Baum, Thomas

    2016-12-01

    This study aimed to evaluate the effect of dose reduction, by means of tube exposure reduction, on bone strength prediction from finite-element (FE) analysis. Fresh thoracic mid-vertebrae specimens (n = 11) were imaged, using multi-detector computed tomography (MDCT), at different intensities of X-ray tube exposures (80, 150, 220 and 500 mAs). Bone mineral density (BMD) was estimated from the mid-slice of each specimen from MDCT images. Differences in image quality and geometry of each specimen were measured. FE analysis was performed on all specimens to predict fracture load. Paired t-tests were used to compare the results obtained, using the highest CT dose (500 mAs) as reference. Dose reduction had no significant impact on FE-predicted fracture loads, with significant correlations obtained with reference to 500 mAs, for 80 mAs (R2  = 0.997, p < 0.001), 150 mAs (R2 = 0.998, p < 0.001) and 220 mAs (R2 = 0.987, p < 0.001). There were no significant differences in volume quantification between the different doses examined. CT imaging radiation dose could be reduced substantially to 64% with no impact on strength estimates obtained from FE analysis. Reduced CT dose will enable early diagnosis and advanced monitoring of osteoporosis and associated fracture risk.

  19. Effects of dose reduction on bone strength prediction using finite element analysis

    PubMed Central

    Anitha, D.; Subburaj, Karupppasamy; Mei, Kai; Kopp, Felix K.; Foehr, Peter; Noel, Peter B.; Kirschke, Jan S.; Baum, Thomas

    2016-01-01

    This study aimed to evaluate the effect of dose reduction, by means of tube exposure reduction, on bone strength prediction from finite-element (FE) analysis. Fresh thoracic mid-vertebrae specimens (n = 11) were imaged, using multi-detector computed tomography (MDCT), at different intensities of X-ray tube exposures (80, 150, 220 and 500 mAs). Bone mineral density (BMD) was estimated from the mid-slice of each specimen from MDCT images. Differences in image quality and geometry of each specimen were measured. FE analysis was performed on all specimens to predict fracture load. Paired t-tests were used to compare the results obtained, using the highest CT dose (500 mAs) as reference. Dose reduction had no significant impact on FE-predicted fracture loads, with significant correlations obtained with reference to 500 mAs, for 80 mAs (R2  = 0.997, p < 0.001), 150 mAs (R2 = 0.998, p < 0.001) and 220 mAs (R2 = 0.987, p < 0.001). There were no significant differences in volume quantification between the different doses examined. CT imaging radiation dose could be reduced substantially to 64% with no impact on strength estimates obtained from FE analysis. Reduced CT dose will enable early diagnosis and advanced monitoring of osteoporosis and associated fracture risk. PMID:27934902

  20. The prediction of transmitted dose distributions using a 3D treatment planning system.

    PubMed

    Reich, P; Bezak, E; Mohammadi, M; Fog, L

    2006-03-01

    Patient dose verification is becoming increasingly important with the advent of new complex radiotherapy techniques such as conformal radiotherapy (CRT) and intensity-modulated radiotherapy (IMRT). An electronic portal imaging device (EPID) has potential application for in vivo dosimetry. In the current work, an EPID has been modelled using a treatment planning system (TPS) to predict transmitted dose maps. A thin slab of RW3 material used to initially represent the EPID. A homogeneous RW3 phantom and the thin RW3 slab placed at a clinical distance away from the phantom were scanned using a CT simulator. The resulting CT images were transferred via DICOM to the TPS and the density of the CT data corresponding to the thin RW3 slab was changed to 1 g/cm3. Transmitted dose maps (TDMs) in the modelled EPID were calculated by the TPS using the collapsed-cone (C-C) convolution superposition (C/S) algorithm. A 6 MV beam was used in the simulation to deliver 300 MU to the homogenous phantom using an isocentric and SSD (source-to-surface) technique. The phantom thickness was varied and the calculated TDMs in the modelled EPID were compared with corresponding measurements obtained from a calibrated scanning liquid-filled ionisation chamber (SLIC) EPID. The two TDMs were compared using the gamma evaluation technique of Low et al. The predicted and measured TDMs agree to within 2 % (averaged over all phantom thicknesses) on the central beam axis. More than 90 % of points in the dose maps (excluding field edges) produce a gamma index less than or equal to 1, for dose difference (averaged over all phantom thicknesses), and distance-to-agreement criteria of 4 %, 3.8 mm, respectively. In addition, the noise level on the central axis in the predicted dose maps is less than 0.1 %. We found that phantom thickness changes of approximately 1 mm, which correspond to dose changes on the central beam axis of less than 0.6 %, can be detected in the predicted transmitted dose distributions.

  1. Prediction analysis of dose equivalent responses of neutron dosemeters used at a MOX fuel facility.

    PubMed

    Tsujimura, N; Yoshida, T; Takada, C

    2011-07-01

    To predict how accurately neutron dosemeters can measure the neutron dose equivalent (rate) in MOX fuel fabrication facility work environments, the dose equivalent responses of neutron dosemeters were calculated by the spectral folding method. The dosemeters selected included two types of personal dosemeter, namely a thermoluminescent albedo neutron dosemeter and an electronic neutron dosemeter, three moderator-based neutron survey meters, and one special instrument called an H(p)(10) monitor. The calculations revealed the energy dependences of the responses expected within the entire range of neutron spectral variations observed in neutron fields at workplaces.

  2. Standard error of inverse prediction for dose-response relationship: approximate and exact statistical inference.

    PubMed

    Demidenko, Eugene; Williams, Benjamin B; Flood, Ann Barry; Swartz, Harold M

    2013-05-30

    This paper develops a new metric, the standard error of inverse prediction (SEIP), for a dose-response relationship (calibration curve) when dose is estimated from response via inverse regression. SEIP can be viewed as a generalization of the coefficient of variation to regression problem when x is predicted using y-value. We employ nonstandard statistical methods to treat the inverse prediction, which has an infinite mean and variance due to the presence of a normally distributed variable in the denominator. We develop confidence intervals and hypothesis testing for SEIP on the basis of the normal approximation and using the exact statistical inference based on the noncentral t-distribution. We derive the power functions for both approaches and test them via statistical simulations. The theoretical SEIP, as the ratio of the regression standard error to the slope, is viewed as reciprocal of the signal-to-noise ratio, a popular measure of signal processing. The SEIP, as a figure of merit for inverse prediction, can be used for comparison of calibration curves with different dependent variables and slopes. We illustrate our theory with electron paramagnetic resonance tooth dosimetry for a rapid estimation of the radiation dose received in the event of nuclear terrorism.

  3. Heliocentric Potential (HCP) Prediction Model for Nowscast of Aviation Radiation Dose

    NASA Astrophysics Data System (ADS)

    Hwang, Junga; Kim, Kyung-Chan; Dokgo, Kyunghwan; Choi, Enjin; Kim, Hang-Pyo

    2015-03-01

    It is well known that the space radiation dose over the polar route should be carefully considered especially when the space weather shows sudden disturbances such as CME and flares. The National Meteorological Satellite Center (NMSC) and Korea Astronomy and Space Science Institute (KASI) recently established a basis for a space radiation service for the public by developing a space radiation prediction model and heliocentric potential (HCP) prediction model. The HCP value is used as a critical input value of the CARI-6 and CARI-6M programs, which estimate the aviation route dose. The CARI-6/6M is the most widely used and confidential program that is officially provided by the U.S. Federal Aviation Administration (FAA). The HCP value is given one month late in the FAA official webpage, making it difficult to obtain real-time information on the aviation route dose. In order to overcome this limitation regarding time delay, we developed a HCP prediction model based on the sunspot number variation. In this paper, we focus on the purpose and process of our HCP prediction model development. Finally, we find the highest correlation coefficient of 0.9 between the monthly sunspot number and the HCP value with an eight month time shift.

  4. Optimization of human dose prediction by using quantitative and translational pharmacology in drug discovery.

    PubMed

    Bueters, Tjerk; Gibson, Christopher; Visser, Sandra A G

    2015-01-01

    In this perspective article, we explain how quantitative and translational pharmacology, when well-implemented, is believed to lead to improved clinical candidates and drug targets that are differentiated from current treatment options. Quantitative and translational pharmacology aims to build and continuously improve the quantitative relationship between drug exposure, target engagement, efficacy, safety and its interspecies relationship at every phase of drug discovery. Drug hunters should consider and apply these concepts to develop compounds with a higher probability of interrogating the clinical biological hypothesis. We offer different approaches to set an initial effective concentration or pharmacokinetic-pharmacodynamic target in man and to predict human pharmacokinetics that determine together the predicted human dose and dose schedule. All concepts are illustrated with ample literature examples.

  5. A two-dimensional matrix correction for off-axis portal dose prediction errors

    SciTech Connect

    Bailey, Daniel W.; Kumaraswamy, Lalith; Bakhtiari, Mohammad; Podgorsak, Matthew B.

    2013-05-15

    Purpose: This study presents a follow-up to a modified calibration procedure for portal dosimetry published by Bailey et al. ['An effective correction algorithm for off-axis portal dosimetry errors,' Med. Phys. 36, 4089-4094 (2009)]. A commercial portal dose prediction system exhibits disagreement of up to 15% (calibrated units) between measured and predicted images as off-axis distance increases. The previous modified calibration procedure accounts for these off-axis effects in most regions of the detecting surface, but is limited by the simplistic assumption of radial symmetry. Methods: We find that a two-dimensional (2D) matrix correction, applied to each calibrated image, accounts for off-axis prediction errors in all regions of the detecting surface, including those still problematic after the radial correction is performed. The correction matrix is calculated by quantitative comparison of predicted and measured images that span the entire detecting surface. The correction matrix was verified for dose-linearity, and its effectiveness was verified on a number of test fields. The 2D correction was employed to retrospectively examine 22 off-axis, asymmetric electronic-compensation breast fields, five intensity-modulated brain fields (moderate-high modulation) manipulated for far off-axis delivery, and 29 intensity-modulated clinical fields of varying complexity in the central portion of the detecting surface. Results: Employing the matrix correction to the off-axis test fields and clinical fields, predicted vs measured portal dose agreement improves by up to 15%, producing up to 10% better agreement than the radial correction in some areas of the detecting surface. Gamma evaluation analyses (3 mm, 3% global, 10% dose threshold) of predicted vs measured portal dose images demonstrate pass rate improvement of up to 75% with the matrix correction, producing pass rates that are up to 30% higher than those resulting from the radial correction technique alone. As in

  6. A model predicting fluindione dose requirement in elderly inpatients including genotypes, body weight, and amiodarone.

    PubMed

    Moreau, Caroline; Pautas, Eric; Duverlie, Charlotte; Berndt, Celia; Andro, Marion; Mahé, Isabelle; Emmerich, Joseph; Lacut, Karine; Le Gal, Grégoire; Peyron, Isabelle; Gouin-Thibault, Isabelle; Golmard, Jean-Louis; Loriot, Marie-Anne; Siguret, Virginie

    2014-04-01

    Indandione VKAs have been widely used for decades, especially in Eastern Europe and France. Contrary to coumarin VKAs, the relative contribution of individual factors to the indandione-VKA response is poorly known. In the present multicentre study, we sought to develop and validate a model including genetic and non-genetic factors to predict the daily fluindione dose requirement in elderly patients in whom VKA dosing is challenging. We prospectively recorded clinical and therapeutic data in 230 Caucasian inpatients mean aged 85 ± 6 years, who had reached international normalized ratio stabilisation (range 2.0-3.0) on fluindione. In the derivation cohort (n=156), we analysed 13 polymorphisms in seven genes potentially involved in the pharmacological effect or vitamin-K cycle (VKORC1, CYP4F2, EPHX1) and fluindione metabolism/transport (CYP2C9, CYP2C19, CYP3A5, ABCB1). We built a regression model incorporating non-genetic and genetic data and evaluated the model performances in a separate cohort (n=74).Body-weight, amiodarone intake, VKORC1, CYP4F2, ABCB1 genotypes were retained in the final model, accounting for 31.5% of dose variability. None influence of CYP2C9 was observed. Our final model showed good performances: in 83.3% of the validation cohort patients, the dose was accurately predicted within 5 mg, i.e.the usual step used for adjusting fluindione dosage. In conclusion, in addition to body-weight and amiodarone-intake, pharmacogenetic factors (VKORC1, CYP4F2, ABCB1) related to the pharmacodynamic effect and transport of fluindione significantly influenced the dose requirement in elderly patients while CYP2C9 did not. Studies are required to know whether fluindione could be an alternative VKA in carriers of polymorphic CYP2C9 alleles, hypersensitive to coumarins.

  7. In silico models for the prediction of dose-dependent human hepatotoxicity

    NASA Astrophysics Data System (ADS)

    Cheng, Ailan; Dixon, Steven L.

    2003-12-01

    The liver is extremely vulnerable to the effects of xenobiotics due to its critical role in metabolism. Drug-induced hepatotoxicity may involve any number of different liver injuries, some of which lead to organ failure and, ultimately, patient death. Understandably, liver toxicity is one of the most important dose-limiting considerations in the drug development cycle, yet there remains a serious shortage of methods to predict hepatotoxicity from chemical structure. We discuss our latest findings in this area and present a new, fully general in silico model which is able to predict the occurrence of dose-dependent human hepatotoxicity with greater than 80% accuracy. Utilizing an ensemble recursive partitioning approach, the model classifies compounds as toxic or non-toxic and provides a confidence level to indicate which predictions are most likely to be correct. Only 2D structural information is required and predictions can be made quite rapidly, so this approach is entirely appropriate for data mining applications and for profiling large synthetic and/or virtual libraries.

  8. Slow sluggish cognitive tempo symptoms are associated with poorer academic performance in children with ADHD.

    PubMed

    Tamm, Leanne; Garner, Annie A; Loren, Richard E A; Epstein, Jeffery N; Vaughn, Aaron J; Ciesielski, Heather A; Becker, Stephen P

    2016-08-30

    Sluggish cognitive tempo (SCT) symptoms may confer risk for academic impairment in attention-deficit/hyperactivity disorder (ADHD). We investigated SCT in relation to academic performance and impairment in 252 children (ages 6-12, 67% boys) with ADHD. Parents and teachers completed SCT and academic impairment ratings, and achievement in reading, math, and spelling was assessed. Simultaneous regressions controlling for IQ, ADHD, and comorbidities were conducted. Total SCT predicted parent-rated impairments in writing, mathematics, and overall school but not reading. Parent-rated SCT Slow predicted poorer reading and spelling, but not math achievement. Teacher-rated SCT Slow predicted poorer spelling and math, but not reading achievement. Parent-rated SCT Slow predicted greater academic impairment ratings across all domains, whereas teacher-rated SCT Slow predicted greater impairment in writing only. Age and gender did not moderate these relationships with the exception of math impairment; SCT slow predicted math impairment for younger but not older children. Parent and teacher SCT Sleepy and Daydreamy ratings were not significant predictors. SCT Slow appears to be uniquely related to academic problems in ADHD, and may be important to assess and potentially target in intervention. More work is needed to better understand the nature of SCT Slow symptoms in relation to inattention and amotivation.

  9. Factors for Predicting Rectal Dose of High-Dose-Rate Intracavitary Brachytherapy After Pelvic Irradiation in Patients With Cervical Cancer: A Retrospective Study With Radiography-Based Dosimetry

    SciTech Connect

    Huang Engyen; Wang Chongjong; Lan Jenhong; Chen Huichun; Fang Fumin; Hsu, H.-C.; Huang Yujie; Wang Changyu; Wang Yuming

    2010-02-01

    Purpose: To evaluate the predictive factors for rectal dose of the first fraction of high-dose-rate intracavitary brachytherapy (HDR-ICBT) in patients with cervical cancer. Methods and Materials: From March 1993 through February 2008, 946 patients undergoing pelvic irradiation and HDR-ICBT were analyzed. Examination under anesthesia (EUA) at the first implantation of the applicator was usually performed in the early period. Rectal point was determined radiographically according to the 38th Report of the International Commission of Radiation Units and Measurements (ICRU). The ICRU rectal dose (PRD) as a percentage of point A dose was calculated; multiple linear regression models were used to predict PRD. Results: Factors influencing successful rectal dose calculation were EUA (p < 0.001) and absence of diabetes (p = 0.047). Age (p < 0.001), body weight (p = 0.002), diabetes (p = 0.020), and EUA (p < 0.001) were independent factors for the PRD. The predictive equation derived from the regression model was PRD (%) = 57.002 + 0.443 x age (years) - 0.257 x body weight (kg) + 6.028 x diabetes (no: 0; yes: 1) - 8.325 x EUA (no: 0; yes: 1) Conclusion: Rectal dose at the first fraction of HDR-ICBT is positively influenced by age and diabetes, and negatively correlated with EUA and body weight. A small fraction size at point A may be considered in patients with a potentially high rectal dose to reduce the biologically effective dose if the ICRU rectal dose has not been immediately obtained in the first fraction of HDR-ICBT.

  10. Application of Machine-Learning Models to Predict Tacrolimus Stable Dose in Renal Transplant Recipients

    PubMed Central

    Tang, Jie; Liu, Rong; Zhang, Yue-Li; Liu, Mou-Ze; Hu, Yong-Fang; Shao, Ming-Jie; Zhu, Li-Jun; Xin, Hua-Wen; Feng, Gui-Wen; Shang, Wen-Jun; Meng, Xiang-Guang; Zhang, Li-Rong; Ming, Ying-Zi; Zhang, Wei

    2017-01-01

    Tacrolimus has a narrow therapeutic window and considerable variability in clinical use. Our goal was to compare the performance of multiple linear regression (MLR) and eight machine learning techniques in pharmacogenetic algorithm-based prediction of tacrolimus stable dose (TSD) in a large Chinese cohort. A total of 1,045 renal transplant patients were recruited, 80% of which were randomly selected as the “derivation cohort” to develop dose-prediction algorithm, while the remaining 20% constituted the “validation cohort” to test the final selected algorithm. MLR, artificial neural network (ANN), regression tree (RT), multivariate adaptive regression splines (MARS), boosted regression tree (BRT), support vector regression (SVR), random forest regression (RFR), lasso regression (LAR) and Bayesian additive regression trees (BART) were applied and their performances were compared in this work. Among all the machine learning models, RT performed best in both derivation [0.71 (0.67–0.76)] and validation cohorts [0.73 (0.63–0.82)]. In addition, the ideal rate of RT was 4% higher than that of MLR. To our knowledge, this is the first study to use machine learning models to predict TSD, which will further facilitate personalized medicine in tacrolimus administration in the future. PMID:28176850

  11. Application of Machine-Learning Models to Predict Tacrolimus Stable Dose in Renal Transplant Recipients.

    PubMed

    Tang, Jie; Liu, Rong; Zhang, Yue-Li; Liu, Mou-Ze; Hu, Yong-Fang; Shao, Ming-Jie; Zhu, Li-Jun; Xin, Hua-Wen; Feng, Gui-Wen; Shang, Wen-Jun; Meng, Xiang-Guang; Zhang, Li-Rong; Ming, Ying-Zi; Zhang, Wei

    2017-02-08

    Tacrolimus has a narrow therapeutic window and considerable variability in clinical use. Our goal was to compare the performance of multiple linear regression (MLR) and eight machine learning techniques in pharmacogenetic algorithm-based prediction of tacrolimus stable dose (TSD) in a large Chinese cohort. A total of 1,045 renal transplant patients were recruited, 80% of which were randomly selected as the "derivation cohort" to develop dose-prediction algorithm, while the remaining 20% constituted the "validation cohort" to test the final selected algorithm. MLR, artificial neural network (ANN), regression tree (RT), multivariate adaptive regression splines (MARS), boosted regression tree (BRT), support vector regression (SVR), random forest regression (RFR), lasso regression (LAR) and Bayesian additive regression trees (BART) were applied and their performances were compared in this work. Among all the machine learning models, RT performed best in both derivation [0.71 (0.67-0.76)] and validation cohorts [0.73 (0.63-0.82)]. In addition, the ideal rate of RT was 4% higher than that of MLR. To our knowledge, this is the first study to use machine learning models to predict TSD, which will further facilitate personalized medicine in tacrolimus administration in the future.

  12. Application of Machine-Learning Models to Predict Tacrolimus Stable Dose in Renal Transplant Recipients

    NASA Astrophysics Data System (ADS)

    Tang, Jie; Liu, Rong; Zhang, Yue-Li; Liu, Mou-Ze; Hu, Yong-Fang; Shao, Ming-Jie; Zhu, Li-Jun; Xin, Hua-Wen; Feng, Gui-Wen; Shang, Wen-Jun; Meng, Xiang-Guang; Zhang, Li-Rong; Ming, Ying-Zi; Zhang, Wei

    2017-02-01

    Tacrolimus has a narrow therapeutic window and considerable variability in clinical use. Our goal was to compare the performance of multiple linear regression (MLR) and eight machine learning techniques in pharmacogenetic algorithm-based prediction of tacrolimus stable dose (TSD) in a large Chinese cohort. A total of 1,045 renal transplant patients were recruited, 80% of which were randomly selected as the “derivation cohort” to develop dose-prediction algorithm, while the remaining 20% constituted the “validation cohort” to test the final selected algorithm. MLR, artificial neural network (ANN), regression tree (RT), multivariate adaptive regression splines (MARS), boosted regression tree (BRT), support vector regression (SVR), random forest regression (RFR), lasso regression (LAR) and Bayesian additive regression trees (BART) were applied and their performances were compared in this work. Among all the machine learning models, RT performed best in both derivation [0.71 (0.67–0.76)] and validation cohorts [0.73 (0.63–0.82)]. In addition, the ideal rate of RT was 4% higher than that of MLR. To our knowledge, this is the first study to use machine learning models to predict TSD, which will further facilitate personalized medicine in tacrolimus administration in the future.

  13. Absorbed Dose Determination Using Experimental and Analytical Predictions of X-Ray Spectra

    NASA Technical Reports Server (NTRS)

    Edwards, D. L.; Carruth, Ralph (Technical Monitor)

    2001-01-01

    Electron beam welding in a vacuum is a technology that NASA is investigating as a joining technique for manufacture of space structures. This investigation characterizes the x-ray environment due to operation of an in-vacuum electron beam welding tool and provides recommendations for adequate shielding for astronauts performing the in-vacuum electron beam welding. NASA, in a joint venture with the Russian Space Agency, was scheduled to perform a series of welding in space experiments on board the U.S. Space Shuttle. This series of experiments was named the international space welding experiment (ISWE). The hardware associated with the ISWE was leased to NASA by the Paton Welding Institute (PWI) in Ukraine for ground-based welding experiments in preparation for flight. Two ground tests were scheduled, using the ISWE electron beam welding tool, to characterize the radiation exposure to an astronaut during the operation of the ISWE. These radiation exposure tests used thermoluminescence dosimeters (TLD's) shielded with material currently used by astronauts during extravehicular activities to measure the radiation dose. The TLD's were exposed to x-ray radiation generated by operation of the ISWE in-vacuum electron beam welding tool. This investigation was the first known application of TLD's to measure absorbed dose from x rays of energy less than 10 keV. The ISWE hardware was returned to Ukraine before the issue of adequate shielding for the astronauts was completely verified. Therefore, alternate experimental and analytical methods were developed to measure and predict the x-ray spectral and intensity distribution generated by ISWE electron beam impact with metal. These x-ray spectra were normalized to an equivalent ISWE exposure, then used to calculate the absorbed radiation dose to astronauts. These absorbed dose values were compared to TLD measurements obtained during actual operation of the ISWE in-vacuum electron beam welding tool. The calculated absorbed dose

  14. Serum Creatinine Versus Plasma Methotrexate Levels to Predict Toxicities in Children Receiving High-dose Methotrexate.

    PubMed

    Tiwari, Priya; Thomas, M K; Pathania, Subha; Dhawan, Deepa; Gupta, Y K; Vishnubhatla, Sreenivas; Bakhshi, Sameer

    2015-01-01

    Facilities for measuring methotrexate (MTX) levels are not available everywhere, potentially limiting administration of high-dose methotrexate (HDMTX). We hypothesized that serum creatinine alteration after HDMTX administration predicts MTX clearance. Overall, 122 cycles in 50 patients of non-Hodgkin lymphoma or acute lymphoblastic leukemia aged ≤18 years receiving HDMTX were enrolled prospectively. Plasma MTX levels were measured at 12, 24, 36, 48, 60, and 72 hours; serum creatinine was measured at baseline, 24, 48, and 72 hours. Correlation of plasma MTX levels with creatinine levels and changes in creatinine from baseline (Δ creatinine) were evaluated. Plasma MTX levels at 72 hours showed positive correlation with serum creatinine at 48 hours (P = .011) and 72 hours (P = .013) as also Δ creatinine at 48 hours (P = .042) and 72 hours (P = .045). However, cut-off value of either creatinine or Δ creatinine could not be established to reliably predict delayed MTX clearance. Greater than 50% Δ creatinine at 48 and 72 hours significantly predicted grade 3/4 leucopenia (P = .036 and P = .001, respectively) and thrombocytopenia (P = .012 and P = .009, respectively) but not mucositis (P = .827 and P = .910, respectively). Delayed MTX elimination did not predict any grade 3/4 toxicity. In spite of demonstration of significant correlation between serum creatinine and Δ creatinine with plasma MTX levels at 72 hours, cut-off value of either variable to predict MTX delay could not be established. Thus, either of these cannot be used as a surrogate for plasma MTX estimation. Interestingly, Δ creatinine effectively predicted hematological toxicities, which were not predicted by delayed MTX clearance.

  15. Predictive factors for anti-HBs status after 1 booster dose of hepatitis B vaccine

    PubMed Central

    Lu, I-Cheng; Jean, Mei-Chu Yen; Lin, Chi-Wei; Chen, Wei-Hung; Perng, Daw-Shyong; Lin, Chih-Wen; Chuang, Hung-Yi

    2016-01-01

    Abstract In Taiwan, infants need to receive 3 doses of hepatitis B virus (HBV) vaccine under the public health policy from the government. However, there are many young adults who even though received complete HBV vaccination in their childhood would lose the positive response of anti-hepatitis B surface antibody (HBs) and need the booster dose of HBV vaccine. The aim of our study is to determine the powerful predictive factor for screening the candidates who need only 1 booster dose of HB vaccine then they can regain positive postbooster anti-HBs status (≧10 mIU/mL) or protective postbooster anti-HBs status (≧100 mIU/mL). We recruited 103 university freshmen who were born after July 1986 with complete HBV vaccination in childhood, but displayed negative results for hepatitis B surface antigen and anti-HBs levels at their health examinations upon university entry. They received 1 booster dose of HB vaccine, and their anti-HBs titers were rechecked 4 weeks after the booster administration. Multivariate analysis logistic regression for positive postbooster anti-HBs status (≧10 mIU/mL, model 1) and protective postbooster anti-HBs status (≧100 mIU/mL, model 2) was done with predictive factors of prebooster anti-HBs level, body mass index, serum glutamate pyruvate transaminase level, and sex. Twenty-four students got positive postbooster anti-HBs status (10–100 mIU/mL) and 50 students got protective postbooster anti-HBs status (≧100 mIU/mL). In the model of multivariate analysis logistic regression for positive postbooster anti-HBs status (≧10 mIU/mL), prebooster anti-HBs level was the strongest predictive factor. The odds ratio was 218.645 and the P value was 0.001. Even in the model of multivariate analysis logistic regression for protective postbooster anti-HBs status (≧100 mIU/mL), prebooster anti-HBs level was still the strongest predictive factor, but the odds ratio of a protective booster effect was 2.143, with 95% confidence

  16. Predictive factors for anti-HBs status after 1 booster dose of hepatitis B vaccine.

    PubMed

    Lu, I-Cheng; Jean, Mei-Chu Yen; Lin, Chi-Wei; Chen, Wei-Hung; Perng, Daw-Shyong; Lin, Chih-Wen; Chuang, Hung-Yi

    2016-09-01

    In Taiwan, infants need to receive 3 doses of hepatitis B virus (HBV) vaccine under the public health policy from the government. However, there are many young adults who even though received complete HBV vaccination in their childhood would lose the positive response of anti-hepatitis B surface antibody (HBs) and need the booster dose of HBV vaccine. The aim of our study is to determine the powerful predictive factor for screening the candidates who need only 1 booster dose of HB vaccine then they can regain positive postbooster anti-HBs status (≧10 mIU/mL) or protective postbooster anti-HBs status (≧100 mIU/mL).We recruited 103 university freshmen who were born after July 1986 with complete HBV vaccination in childhood, but displayed negative results for hepatitis B surface antigen and anti-HBs levels at their health examinations upon university entry. They received 1 booster dose of HB vaccine, and their anti-HBs titers were rechecked 4 weeks after the booster administration. Multivariate analysis logistic regression for positive postbooster anti-HBs status (≧10 mIU/mL, model 1) and protective postbooster anti-HBs status (≧100 mIU/mL, model 2) was done with predictive factors of prebooster anti-HBs level, body mass index, serum glutamate pyruvate transaminase level, and sex.Twenty-four students got positive postbooster anti-HBs status (10-100 mIU/mL) and 50 students got protective postbooster anti-HBs status (≧100 mIU/mL). In the model of multivariate analysis logistic regression for positive postbooster anti-HBs status (≧10 mIU/mL), prebooster anti-HBs level was the strongest predictive factor. The odds ratio was 218.645 and the P value was 0.001. Even in the model of multivariate analysis logistic regression for protective postbooster anti-HBs status (≧100 mIU/mL), prebooster anti-HBs level was still the strongest predictive factor, but the odds ratio of a protective booster effect was 2.143, with 95% confidence interval between 1

  17. BIODOSE: a code for predicting the dose to man from radionuclides released from underground nuclear waste repositories

    SciTech Connect

    Bonner, N.A.; Ng, Y.C.

    1980-03-01

    The BIODOSE computer program simulates the environmental transport of radionuclides released to surface water and predicts the resulting dosage to humans. This report describes the program and discusses its use in the evaluation of nuclear waste repositories. The methods used to estimate dose are examined critically, and the most important parameters in each stage of the calculations are identified as an aid in planning for measurements in the field. Dose predictions from releases of nuclear waste to a large northwestern river (the baseline river) are presented to point out the nuclides, compartments and pathways that contribute most to the hazard as a function of waste storage time. Predictions for five other water systems are presented to identify the most important system parameters that determine the concentrations of individual nuclides in compartments and the resultant dose. The uncertainties in the biological parameters for dose prediction are identified, and changes in current values are suggested. Various ways of reporting dose estimates for radiological safety assessments are discussed. Additional work needed to improve the dose predictions from BIODOSE and specific areas and steps to improve our capabilities to assess the environmental transport of nuclides released from nuclear waste repositories and the resultant dose to man are suggested.

  18. Comparison of enhanced device response and predicted x-ray dose enhancement effects on MOS oxides

    SciTech Connect

    Fleetwood, D.M.; Beutler, D.E.; Lorence, L.J. Jr.; Draper, B.L.; Brown, D.B.; Riewe, L.C.; Rosenstock, H.B.; Knott, D.P.

    1988-12-01

    The response of MOS capacitors to low- and medium-energy x-ray irradiation is investigated as a function of gate material (TaSi or Al), oxide thickness, and electric field. Measured device response is compared with predictions based on discrete ordinates and Monte Carlo code simulations of dose enhancement effects, coupled with recent estimates of electron-hole recombination in MOS oxides. In comparisons of 10-keV x-ray and Co-60 irradiations of Al-gate MOS capacitors at an oxide electric field of 1 MV/cm, it is found that predictions and experiments agree to within better than 20 percent for oxide thicknesses ranging from 35 to 1060 nm. For capacitors having TaSi/Al gates, predictions and experiments agree to within better than 30 percent at 1 MV/cm, with the largest differences occurring for 35-nm gate oxides. At other electric fields, the disagreement between experiment and prediction increases significantly for both Al- and TaSi/Al-gate capacitors, and can be greater than a factor of 2 at applied electric fields below 0.1 MV/cm. For medium energy (-- 100 keV average photon energy) x-ray irradiations, the enhanced device response exhibits a much stronger dependence on endpoint bremsstrahlung energy than expected from TIGERP or CEPXS/ONETRAN simulations. Implications for hardness assurance testing are discussed.

  19. Effects of positioning uncertainty and breathing on dose delivery and radiation pneumonitis prediction in breast cancer.

    PubMed

    Mavroidis, Panayiotis; Axelsson, Sofie; Hyödynmaa, Simo; Rajala, Juha; Pitkänen, Maunu A; Lind, Bengt K; Brahme, Anders

    2002-01-01

    complication probabilities than the original plans. This means that the true expected complications are often underestimated in clinical practice. The lung density variation during breathing is calculated from the maximal change in average density during tidal breathing. The change in density in the lung due to breathing is shown to have almost no influence on the dose distribution in the lung. The proposed treatment-plan adjustments taking positioning uncertainty and breathing effects into account indicate significant deviations in the dose delivery and the predicted lung complications.

  20. Incorporating system latency associated with real-time target tracking radiotherapy in the dose prediction step

    NASA Astrophysics Data System (ADS)

    Roland, Teboh; Mavroidis, Panayiotis; Shi, Chengyu; Papanikolaou, Nikos

    2010-05-01

    System latency introduces geometric errors in the course of real-time target tracking radiotherapy. This effect can be minimized, for example by the use of predictive filters, but cannot be completely avoided. In this work, we present a convolution technique that can incorporate the effect as part of the treatment planning process. The method can be applied independently or in conjunction with the predictive filters to compensate for residual latency effects. The implementation was performed on TrackBeam (Initia Ltd, Israel), a prototype real-time target tracking system assembled and evaluated at our Cancer Institute. For the experimental system settings examined, a Gaussian distribution attributable to the TrackBeam latency was derived with σ = 3.7 mm. The TrackBeam latency, expressed as an average response time, was deduced to be 172 ms. Phantom investigations were further performed to verify the convolution technique. In addition, patient studies involving 4DCT volumes of previously treated lung cancer patients were performed to incorporate the latency effect in the dose prediction step. This also enabled us to effectively quantify the dosimetric and radiobiological impact of the TrackBeam and other higher latency effects on the clinical outcome of a real-time target tracking delivery.

  1. Animal studies on medicinal herbs: predictability, dose conversion and potential value.

    PubMed

    Wojcikowski, Ken; Gobe, Glenda

    2014-01-01

    Animal studies testing medicinal herbs are often misinterpreted by both translational researchers and clinicians due to a lack of information regarding their predictability, human dose equivalent and potential value. The most common mistake is to design or translate an animal study on a milligram per kilogram basis. This can lead to underestimation of the toxicity and/or overestimation of the amount needed for human therapy. Instead, allometric scaling, which involves body surface area, should be used. While the differences in the pharmacokinetic and pharmacodynamic phases between species will inevitably lead to some degree of error in extrapolation of results regardless of the conversion method used, correct design and interpretation of animal studies can provide information that is not able to be provided by in vitro studies, computer modeling or even traditional use.

  2. EPR oxygen images predict tumor control by a 50 percent tumor control radiation dose

    PubMed Central

    Elas, Martyna; Magwood, Jessica M.; Butler, Brandi; Li, Chanel; Wardak, Rona; Barth, Eugene D.; Epel, Boris; Rubinstein, Samuel; Pelizzari, Charles A.; Weichselbaum, Ralph R.; Halpern, Howard J.

    2013-01-01

    Clinical trials to ameliorate hypoxia as a strategy to relieve the radiation resistance it causes have prompted a need to assay the precise extent and location of hypoxia in tumors. Electron Paramagnetic Resonance oxygen imaging (EPR O2 imaging) provides a non-invasive means to address this need. To obtain a preclinical proof of principle that EPR O2 images could predict radiation control, we treated mouse tumors at or near doses required to achieve 50 percent control (TCD50). Mice with FSa fibrosarcoma or MCa4 carcinoma were subjected to EPR O2 imaging and immediately radiated to a TCD50 or TCD50 ±10 Gy.. Statistical analysis was permitted by collection of ~ 1300 tumor pO2 image voxels, including the fraction of tumor voxels with pO2 less than 10 mm Hg (HF10). Tumors were followed for 90 days (FSa) or 120 days (MCa4) to determine local control or failure. HF10 obtained from EPR images showed statistically significant differences between tumors that were controlled by the TCD50 and those that were not controlled for both FSa and MCa4. Kaplan-Meier analysis of both types of tumors showed ~90% of mildly hypoxic tumors were controlled (HF10<10%), and only 37% (FSA) and 23% (MCa4) tumors controlled if hypoxic. EPR pO2 image voxel distributions in these ~0.5 ml tumors provide a prediction of radiation curability independent of radiation dose. These data confirm the significance of EPR pO2 hypoxic fractions. The ~90% control of low HF10 tumors argue that ½ ml subvolumes of tumors may be more sensitive to radiation and may need less radiation for high tumor control rates. PMID:23861469

  3. Spatial Prediction of Coxiella burnetii Outbreak Exposure via Notified Case Counts in a Dose-Response Model.

    PubMed

    Brooke, Russell J; Kretzschmar, Mirjam E E; Hackert, Volker; Hoebe, Christian J P A; Teunis, Peter F M; Waller, Lance A

    2017-01-01

    We develop a novel approach to study an outbreak of Q fever in 2009 in the Netherlands by combining a human dose-response model with geostatistics prediction to relate probability of infection and associated probability of illness to an effective dose of Coxiella burnetii. The spatial distribution of the 220 notified cases in the at-risk population are translated into a smooth spatial field of dose. Based on these symptomatic cases, the dose-response model predicts a median of 611 asymptomatic infections (95% range: 410, 1,084) for the 220 reported symptomatic cases in the at-risk population; 2.78 (95% range: 1.86, 4.93) asymptomatic infections for each reported case. The low attack rates observed during the outbreak range from (Equation is included in full-text article.)to (Equation is included in full-text article.). The estimated peak levels of exposure extend to the north-east from the point source with an increasing proportion of asymptomatic infections further from the source. Our work combines established methodology from model-based geostatistics and dose-response modeling allowing for a novel approach to study outbreaks. Unobserved infections and the spatially varying effective dose can be predicted using the flexible framework without assuming any underlying spatial structure of the outbreak process. Such predictions are important for targeting interventions during an outbreak, estimating future disease burden, and determining acceptable risk levels.

  4. Determining Cutoff Point of Ensemble Trees Based on Sample Size in Predicting Clinical Dose with DNA Microarray Data

    PubMed Central

    Karabulut, Erdem; Alpar, Celal Reha

    2016-01-01

    Background/Aim. Evaluating the success of dose prediction based on genetic or clinical data has substantially advanced recently. The aim of this study is to predict various clinical dose values from DNA gene expression datasets using data mining techniques. Materials and Methods. Eleven real gene expression datasets containing dose values were included. First, important genes for dose prediction were selected using iterative sure independence screening. Then, the performances of regression trees (RTs), support vector regression (SVR), RT bagging, SVR bagging, and RT boosting were examined. Results. The results demonstrated that a regression-based feature selection method substantially reduced the number of irrelevant genes from raw datasets. Overall, the best prediction performance in nine of 11 datasets was achieved using SVR; the second most accurate performance was provided using a gradient-boosting machine (GBM). Conclusion. Analysis of various dose values based on microarray gene expression data identified common genes found in our study and the referenced studies. According to our findings, SVR and GBM can be good predictors of dose-gene datasets. Another result of the study was to identify the sample size of n = 25 as a cutoff point for RT bagging to outperform a single RT. PMID:28096893

  5. A NEW SEMI-EMPIRICAL AMBIENT TO EFFECTIVE DOSE CONVERSION MODEL FOR THE PREDICTIVE CODE FOR AIRCREW RADIATION EXPOSURE (PCAIRE).

    PubMed

    Dumouchel, T; McCall, M; Lemay, F; Bennett, L; Lewis, B; Bean, M

    2016-12-01

    The Predictive Code for Aircrew Radiation Exposure (PCAIRE) is a semi-empirical code that estimates both ambient dose equivalent, based on years of on-board measurements, and effective dose to aircrew. Currently, PCAIRE estimates effective dose by converting the ambient dose equivalent to effective dose (E/H) using a model that is based on radiation transport calculations and on the radiation weighting factors recommended in International Commission on Radiological Protection (ICRP) 60. In this study, a new semi-empirical E/H model is proposed to replace the existing transport calculation models. The new model is based on flight data measured using a tissue-equivalent proportional counter (TEPC). The measured flight TEPC data are separated into a low- and a high-lineal-energy spectrum using an amplitude-weighted (137)Cs TEPC spectrum. The high-lineal-energy spectrum is determined by subtracting the low-lineal-energy spectrum from the measured flight TEPC spectrum. With knowledge of E/H for the low- and high-lineal-energy spectra, the total E/H is estimated for a given flight altitude and geographic location. The semi-empirical E/H model also uses new radiation weighting factors to align the model with the most recent ICRP 103 recommendations. The ICRP 103-based semi-empirical effective dose model predicts that there is a ∼30 % reduction in dose in comparison with the ICRP 60-based model. Furthermore, the ambient dose equivalent is now a more conservative dose estimate for jet aircraft altitudes in the range of 7-13 km (FL230-430). This new semi-empirical E/H model is validated against E/H predicted from a Monte Carlo N-Particle transport code simulation of cosmic ray propagation through the Earth's atmosphere. Its implementation allows PCAIRE to provide an accurate semi-empirical estimate of the effective dose.

  6. SU-E-T-430: Feasibility Study On Using Overlap Volume Histogram to Predict the Dose Difference by Respiratory Motion

    SciTech Connect

    Shin, D; Kang, S; Kim, D; Kim, T; Kim, K; Cho, M; Suh, T

    2015-06-15

    Purpose: The dose difference between three-dimensional dose (3D dose) and 4D dose which considers motion due to respiratory can be varied according to geometrical relationship between planning target volume (PTV) and organ at risk (OAR). The purpose of the study is to investigate the dose difference between 3D and 4D dose using overlap volume histogram (OVH) which is an indicator that quantify geometrical relationship between a PTV and an OAR. Methods: Five liver cancer patients who previously treated stereotactic body radiotherapy (SBRT) were investigated. Four-dimensional computed tomography (4DCT) images were acquired for all patients. ITV-based treatment planning was performed. 3D dose was calculated on the end-exhale phase image as a reference phase image. 4D dose accumulation was implemented from all phase images using dose warping technique used deformable image registration (DIR) algorithm (Horn and Schunck optical flow) in DIRART. In this study OVH was used to quantify geometrical relationship between a PTV and an OAR. OVH between a PTV and a selected OAR was generated for each patient case and compared for all cases. The dose difference between 3D and 4D dose for normal organ was calculated and compared for all cases according to OVH. Results: The 3D and 4D dose difference for OAR was analyzed using dose-volume histogram (DVH). On the basis of a specific point which corresponds to 10% of OAR volume overlapped with expanded PTV, mean dose difference was 34.56% in minimum OVH distance case and 13.36% in maximum OVH distance case. As the OVH distance increased, mean dose difference between 4D and 3D dose was decreased. Conclusion: The tendency of dose difference variation was verified according to OVH. OVH is seems to be indicator that has a potential to predict the dose difference between 4D and 3D dose. This work was supported by the Radiation Technology R&D program (No. 2013M2A2A7043498) and the Mid-career Researcher Program (2014R1A2A1A10050270) through

  7. PREDICTING THE RISKS OF NEUROTOXIC VOLATILE ORGANIC COMPOUNDS BASED ON TARGET TISSUE DOSE.

    EPA Science Inventory

    Quantitative exposure-dose-response models relate the external exposure of a substance to the dose in the target tissue, and then relate the target tissue dose to production of adverse outcomes. We developed exposure-dose-response models to describe the affects of acute exposure...

  8. Postoperative Pain Management in Latino Families: Parent Beliefs about Analgesics Predict Analgesic Doses Provided to Children

    PubMed Central

    Rosales, Alvina; Fortier, Michelle A.; Campos, Belinda; Kain, Zeev N.

    2015-01-01

    Background/Objectives The present study examined whether parental perceptions of children’s pain impacted home-based pain management following outpatient surgery in a sample of Latino families from low socioeconomic backgrounds. Methods Latino parents of children (n = 161) who underwent outpatient surgery were recruited for this study and completed measures assessing attitudes on pain and analgesic use (Parental Pain Expression Perceptions and Medication Attitudes Questionnaire) before their child’s surgery. Parents also rated their child’s pain after their child’s surgery using the Parent Postoperative Pain Measure and collected data on the amount of analgesics they gave to their child on the first postoperative day. Hierarchical regression analyses examined whether parental attitudes predicted pain assessment and management at home. Results A majority of parents reported multiple misconceptions regarding children’s pain and fears of side effects as well as avoidance of analgesic use. For example, over 80% reported believing that a child always tells their parents when they are in pain. Hierarchical regression analyses found that more fear and avoidance regarding analgesic use for children’s pain predicted parents’ providing fewer doses of analgesic to their children on the first postoperative day (β = −0.21, p = 0.028). Conclusions Preoperative parents’ beliefs regarding analgesics for treatment of children’s pain may adversely impact parent postoperative analgesic administration at home in Latino families. PMID:26792407

  9. Negative communication in psychosis: understanding pathways to poorer patient outcomes.

    PubMed

    Finnegan, Deirdre; Onwumere, Juliana; Green, Catherine; Freeman, Daniel; Garety, Philippa; Kuipers, Elizabeth

    2014-11-01

    High expressed emotion (EE) is a robust predictor of elevated rates of relapse and readmission in schizophrenia. However, far less is known about how high EE leads to poorer patient outcomes. This study was designed to examine links between high EE (criticism), affect, and multidimensional aspects of positive symptoms in patients with psychosis. Thirty-eight individuals with nonaffective psychosis were randomly exposed to proxy high-EE or neutral speech samples and completed self-report measures of affect and psychosis symptoms. Patients reported significant increases in anxiety, anger, and distress after exposure to the proxy high-EE speech sample as well as increases in their appraisals of psychosis symptoms: voice controllability, delusional preoccupation, and conviction. These findings offer further evidence of the potential deleterious impact of a negative interpersonal environment on patient symptoms in psychosis.

  10. Late Fecal Incontinence After High-Dose Radiotherapy for Prostate Cancer: Better Prediction Using Longitudinal Definitions

    SciTech Connect

    Fiorino, Claudio; Rancati, Tiziana; Fellin, Gianni; Vavassori, Vittorio; Cagna, Emanuela; Casanova Borca, Valeria; Girelli, Giuseppe; Menegotti, Loris; Monti, Angelo Filippo; Tortoreto, Francesca; Delle Canne, Stefania; Valdagni, Riccardo

    2012-05-01

    Purpose: To model late fecal incontinence after high-dose prostate cancer radiotherapy (RT) in patients accrued in the AIROPROS (prostate working group of the Italian Association of Radiation Oncology) 0102 trial using different endpoint definitions. Methods and Materials: The self-reported questionnaires (before RT, 1 month after RT, and every 6 months for {<=}3 years after RT) of 586 patients were available. The peak incontinence (P{sub I}NC) and two longitudinal definitions (chronic incontinence [C{sub I}NC], defined as the persistence of Grade 1 or greater incontinence after any Grade 2-3 event; and mean incontinence score [M{sub I}NC], defined as the average score during the 3-year period after RT) were considered. The correlation between the clinical/dosimetric parameters (including rectal dose-volume histograms) and P{sub I}NC (Grade 2 or greater), C{sub I}NC, and M{sub I}NC of {>=}1 were investigated using multivariate logistic analyses. Receiver operating characteristic curves and the area under the curve were used to assess the predictive value of the different multivariate models. Results: Of the 586 patients, 36 with a Grade 1 or greater incontinence score before RT were not included in the present analysis. Of the 550 included patients, 197 (35.8%) had at least one control with a Grade 1 or greater incontinence score (M{sub I}NC >0). Of these 197 patients, 37 (6.7%), 22 (4.0%), and 17 (3.1%) were scored as having P{sub I}NC, M{sub I}NC {>=}1, and C{sub I}NC, respectively. On multivariate analysis, Grade 2 or greater acute incontinence was the only predictor of P{sub I}NC (odds ratio [OR], 5.9; p = .0009). Grade 3 acute incontinence was predictive of C{sub I}NC (OR, 9.4; p = .02), and percentage of the rectal volume receiving >40 Gy of {>=}80% was predictive of a M{sub I}NC of {>=}1 (OR, 3.8; p = .008) and of C{sub I}NC (OR, 3.6; p = .03). Previous bowel disease, previous abdominal/pelvic surgery, and the use of antihypertensive (protective factor

  11. Does heightened fear of crime lead to poorer mental health in new suburbs, or vice versa?

    PubMed

    Foster, Sarah; Hooper, Paula; Knuiman, Matthew; Giles-Corti, Billie

    2016-11-01

    Fear of crime is implicated as a risk factor for poorer mental health, yet few studies have explored whether there is a causal relationship between fear of crime and health, or tested the direction of the relationship. Does, for example, heightened fear of crime lead to poorer mental health, or could poorer mental health exacerbate fear of crime? RESIDE participants in Perth, Australia, completed a questionnaire three years after moving to their neighbourhood (2007-2008, n = 1230), and again four years later (2011-2012, n = 531). The impact of fear of crime on psychological distress (Kessler-6) was examined in SAS using the Proc Mixed procedure (marginal repeated measures model with unrestricted variance pattern). Models controlled for demographics and time, and progressively adjusted for avoidance behaviours (i.e., walking, community participation, social cohesion). This approach was repeated with psychological distress as the independent variable and fear of crime as the outcome. For each increase in one standard deviation (SD) in fear of crime, psychological distress increased by 0.680 (p = 0.0001), however in the reversed models, for each one SD increase in psychological distress, fear of crime increased by 0.152 (p = 0.0001). To help explain these results, temporal order models examined whether baseline values predicted follow-up values. There was a significant association between psychological distress (at baseline) and fear of crime (at follow-up), but no association between fear of crime (at baseline) and psychological distress (at follow-up). The findings suggest a bi-directional relationship exists between fear of crime and mental health, however it appears that higher psychological distress over time leads to higher fear of crime, rather than the reverse. Furthermore, the pathway connecting fear of crime and mental health appears to be direct, rather than via constrained social and physical activities.

  12. LINKING DERMAL MODELING AND LOADING DATA TO PREDICT LONG-TERM DOSES FROM INTERMITTENT DERMAL CONTACT

    EPA Science Inventory

    In this paper we assess dermal exposure and dose resulting from intermittent contact with residue-contaminated surfaces. These estimates require an understanding of (1) the quantitative relationship between exposure and absorbed dose; (2) the impact of intermittent exposure on ...

  13. Prediction of Warfarin Dose Reductions in Puerto Rican Patients, Based on Combinatorial CYP2C9 and VKORC1 Genotypes

    PubMed Central

    Valentin, Isa Ivette; Vazquez, Joan; Rivera-Miranda, Giselle; Seip, Richard L; Velez, Meredith; Kocherla, Mohan; Bogaard, Kali; Cruz-Gonzalez, Iadelisse; Cadilla, Carmen L; Renta, Jessica Y; Felliu, Juan F; Ramos, Alga S; Alejandro-Cowan, Yirelia; Gorowski, Krystyna; Ruaño, Gualberto; Duconge, Jorge

    2012-01-01

    BACKGROUND The influence of CYP2C9 and VKORC1 polymorphisms on warfarin dose has been investigated in white, Asian, and African American populations but not in Puerto Rican Hispanic patients. OBJECTIVE To test the associations between genotypes, international normalized ratio (INR) measurements, and warfarin dosing and gauge the impact of these polymorphisms on warfarin dose, using a published algorithm. METHODS A retrospective warfarin pharmacogenetic association study in 106 Puerto Rican patients was performed. DNA samples from patients were assayed for 12 variants in both CYP2C9 and VKORC1 loci by HILOmet PhyzioType assay. Demographic and clinical nongenetic data were retrospectively collected from medical records. Allele and genotype frequencies were determined and Hardy-Weinberg equilibrium (HWE) was tested. RESULTS Sixty-nine percent of patients were carriers of at least one polymorphism in either the CYP2C9 or the VKORC1 gene. Double, triple, and quadruple carriers accounted for 22%, 5%, and 1%, respectively. No significant departure from HWE was found. Among patients with a given CYP2C9 genotype, warfarin dose requirements declined from GG to AA haplotypes; whereas, within each VKORC1 haplotype, the dose decreased as the number of CYP2C9 variants increased. The presence of these loss-of-function alleles was associated with more out-of-range INR measurements (OR = 1.38) but not with significant INR >4 during the initiation phase. Analyses based on a published pharmacogenetic algorithm predicted dose reductions of up to 4.9 mg/day in carriers and provided better dose prediction in an extreme subgroup of highly sensitive patients, but also suggested the need to improve predictability by developing a customized model for use in Puerto Rican patients. CONCLUSIONS This study laid important groundwork for supporting a prospective pharmacogenetic trial in Puerto Ricans to detect the benefits of incorporating relevant genomic information into a customized DNA

  14. Polonium in size fractionated mainstream cigarette smoke, predicted deposition and associated internal radiation dose.

    PubMed

    Tiwari, M; Sahu, S K; Bhangare, R C; Pandit, G G

    2016-10-01

    In this study, size fractionated mass and (210)Po activity concentrations in mainstream cigarette smoke (MCS) were monitored for three popular cigarette brands. Size segregated collection of MCS was carried out using a cascade type impactor, while mass and (210)Po activity concentration were analyzed gravimetrically and alpha spectrometry (following the radiochemical separation) respectively. Multiple-Path Particle Dosimetry (MPPD V2.11) model is used for prediction of deposition fraction calculations for the MCS deposition in different compartment of human respiratory tract. The activity concentration of (210)Po is founds 10.56 ± 2.46 mBq per cigarette for the tested cigarette brands. (210)Po size distribution indicates most of this associates with fine fraction (Dp < 2.23 μm) of cigarette smoke. The committed annual effective dose to smokers (smoking on an average 20 cigarette a day), considering the (210)Po and (210)Pb concentrations (assuming it is in secular equilibrium with (210)Po) in MCS, was estimated between 0.22 and 0.40 mSv, with mean value of 0.30 mSv for tested cigarette brands. Considering the risk factor of fatal cancer due to radiation exposure of lung (exposure time of 30 years); the average collective estimated fatal cancer risk is estimated as 1.5 × 10(-4) due to (210)Po and (210)Pb exposure to smokers.

  15. Dose-response curve slope helps predict therapeutic potency and breadth of HIV broadly neutralizing antibodies.

    PubMed

    Webb, Nicholas E; Montefiori, David C; Lee, Benhur

    2015-09-29

    A new generation of HIV broadly neutralizing antibodies (bnAbs) with remarkable potency, breadth and epitope diversity has rejuvenated interest in immunotherapeutic strategies. Potencies defined by in vitro IC50 and IC80 values (50 and 80% inhibitory concentrations) figure prominently into the selection of clinical candidates; however, much higher therapeutic levels will be required to reduce multiple logs of virus and impede escape. Here we predict bnAb potency at therapeutic levels by analysing dose-response curve slopes, and show that slope is independent of IC50/IC80 and specifically relates to bnAb epitope class. With few exceptions, CD4-binding site and V3-glycan bnAbs exhibit slopes >1, indicative of higher expected therapeutic effectiveness, whereas V2-glycan, gp41 membrane-proximal external region (MPER) and gp120-gp41 bnAbs exhibit less favourable slopes <1. Our results indicate that slope is one major predictor of both potency and breadth for bnAbs at clinically relevant concentrations, and may better coordinate the relationship between bnAb epitope structure and therapeutic expectations.

  16. Low dose dobutamine echocardiography for predicting functional recovery after coronary revascularisation

    PubMed Central

    Piscione, F; Perrone-Filardi, P; De Luca, G; Prastaro, M; Indolfi, C; Golino, P; Dellegrottaglie, S; Chiariello, M

    2001-01-01

    OBJECTIVE—To evaluate the effects of chronic coronary occlusion on the accuracy of low dose dobutamine echocardiography in predicting recovery of dysfunctional myocardium after revascularisation.
DESIGN—Retrospective study.
SETTING—Tertiary referral centre.
PATIENTS—53 consecutive patients with ⩾ 70% stenosis of the left anterior descending coronary artery (LAD) and regional ventricular dysfunction (group 1, non-occluded LAD; group 2, occluded LAD) who underwent dobutamine echocardiography.
INTERVENTIONS—26 patients underwent coronary artery bypass grafting and 27 had percutaneous transluminal coronary angioplasty.
MAIN OUTCOME MEASURES—Baseline studies before revascularisation included cross sectional echocardiography at rest and during dobutamine infusion (5-10 µg/kg/min), and coronary angiography. The dobutamine study was performed mean (SD) 35 (28) days before revascularisation. Echocardiography at rest was repeated 90 (48) days after revascularisation.
RESULTS—Of 296 dysfunctional segments, 63 in group 1 (43%; 63/146) and 69 in group 2 (46%; 69/150) (NS) improved at follow up. Mean (SD) regional wall motion score index decreased from 1.97 (0.48) (95% confidence interval (CI) 1.01 to 2.93) before revascularisation to 1.74 (0.52) (95% CI 0.70 to 2.78) at follow up in group 1 (p = 0.001), and from 2.12 (0.41) (95% CI 1.30 to 2.98) to 1.88 (0.36) (95% CI 1.16 to 2.60) in group 2 (p = 0.0006). In group 1, sensitivity (87% v 52%; p < 0.0001), negative predictive value (88% v 65%; p = 0.001), and accuracy (77% v 64%; p = 0.01) were all significantly higher than in group 2, despite the angiographic evidence of collaterals in patients with occluded vessels.
CONCLUSIONS—Dobutamine echocardiography shows reduced sensitivity in predicting recovery of dysfunctional myocardium supplied by totally occluded vessels. Thus caution should be used in selecting such patients for revascularisation on the basis of a

  17. Development of Dose-Response Models to Predict the Relationship for Human Toxoplasma gondii Infection Associated with Meat Consumption.

    PubMed

    Guo, Miao; Mishra, Abhinav; Buchanan, Robert L; Dubey, Jitender P; Hill, Dolores E; Gamble, H Ray; Jones, Jeffrey L; Du, Xianzhi; Pradhan, Abani K

    2016-05-01

    Toxoplasma gondii is a protozoan parasite that is responsible for approximately 24% of deaths attributed to foodborne pathogens in the United States. It is thought that a substantial portion of human T. gondii infections is acquired through the consumption of meats. The dose-response relationship for human exposures to T. gondii-infected meat is unknown because no human data are available. The goal of this study was to develop and validate dose-response models based on animal studies, and to compute scaling factors so that animal-derived models can predict T. gondii infection in humans. Relevant studies in literature were collected and appropriate studies were selected based on animal species, stage, genotype of T. gondii, and route of infection. Data were pooled and fitted to four sigmoidal-shaped mathematical models, and model parameters were estimated using maximum likelihood estimation. Data from a mouse study were selected to develop the dose-response relationship. Exponential and beta-Poisson models, which predicted similar responses, were selected as reasonable dose-response models based on their simplicity, biological plausibility, and goodness fit. A confidence interval of the parameter was determined by constructing 10,000 bootstrap samples. Scaling factors were computed by matching the predicted infection cases with the epidemiological data. Mouse-derived models were validated against data for the dose-infection relationship in rats. A human dose-response model was developed as P (d) = 1-exp (-0.0015 × 0.005 × d) or P (d) = 1-(1 + d × 0.003 / 582.414)(-1.479) . Both models predict the human response after consuming T. gondii-infected meats, and provide an enhanced risk characterization in a quantitative microbial risk assessment model for this pathogen.

  18. Prediction of In-Phantom Dose Distribution Using In-Air Neutron Beam Characteristics for Boron Neutron Capture Synovectomy

    SciTech Connect

    Verbeke, Jerome M.; Chen, Allen S.; Vujic, Jasmina L.; Leung, Ka-Ngo

    2000-08-15

    A monoenergetic neutron beam simulation study was carried out to determine the optimal neutron energy range for treatment of rheumatoid arthritis using radiation synovectomy. The goal of the treatment is the ablation of diseased synovial membranes in joints such as knees and fingers. This study focuses on human knee joints. Two figures of merit are used to measure the neutron beam quality, the ratio of the synovium-absorbed dose to the skin-absorbed dose, and the ratio of the synovium-absorbed dose to the bone-absorbed dose. It was found that (a) thermal neutron beams are optimal for treatment and that (b) similar absorbed dose rates and therapeutic ratios are obtained with monodirectional and isotropic neutron beams. Computation of the dose distribution in a human knee requires the simulation of particle transport from the neutron source to the knee phantom through the moderator. A method was developed to predict the dose distribution in a knee phantom from any neutron and photon beam spectra incident on the knee. This method was revealed to be reasonably accurate and enabled one to reduce the particle transport simulation time by a factor of 10 by modeling the moderator only.

  19. A Novel Method to Incorporate the Spatial Location of the Lung Dose Distribution into Predictive Radiation Pneumonitis Modeling

    SciTech Connect

    Vinogradskiy, Yevgeniy; Tucker, Susan L.; Liao, Zhongxing; Martel, Mary K.

    2012-03-15

    Purpose: Studies have proposed that patients who receive radiation therapy to the base of the lung are more susceptible to radiation pneumonitis than patients who receive therapy to the apex of the lung. The primary purpose of the present study was to develop a novel method to incorporate the lung dose spatial information into a predictive radiation pneumonitis model. A secondary goal was to apply the method to a 547 lung cancer patient database to determine whether including the spatial information could improve the fit of our model. Methods and Materials: The three-dimensional dose distribution of each patient was mapped onto one common coordinate system. The boundaries of the coordinate system were defined by the extreme points of each individual patient lung. Once all dose distributions were mapped onto the common coordinate system, the spatial information was incorporated into a Lyman-Kutcher-Burman predictive radiation pneumonitis model. Specifically, the lung dose voxels were weighted using a user-defined spatial weighting matrix. We investigated spatial weighting matrices that linearly scaled each dose voxel according to the following orientations: superior-inferior, anterior-posterior, medial-lateral, left-right, and radial. The model parameters were fit to our patient cohort with the endpoint of severe radiation pneumonitis. The spatial dose model was compared against a conventional dose-volume model to determine whether adding a spatial component improved the fit of the model. Results: Of the 547 patients analyzed, 111 (20.3%) experienced severe radiation pneumonitis. Adding in a spatial parameter did not significantly increase the accuracy of the model for any of the weighting schemes. Conclusions: A novel method was developed to investigate the relationship between the location of the deposited lung dose and pneumonitis rate. The method was applied to a patient database, and we found that for our patient cohort, the spatial location does not influence

  20. [Perspective of predictive toxicity assessment of in vivo repeated dose toxicity using structural activity relationship].

    PubMed

    Ono, Atsushi

    2010-01-01

    Tens of thousands of existing chemicals have been widely used for manufacture, agriculture, household and other purposes in worldwide. Only approximately 10% of chemicals have been assessed for human health hazard. The health hazard assessment of residual large number of chemicals for which little or no information of their toxicity is available is urgently needed for public health. However, the conduct of traditional toxicity tests which involves using animals for all of these chemicals would be economically impractical and ethically unacceptable. (Quantitative) Structure-Activity Relationships [(Q)SARs] are expected as method to have the potential to estimate hazards of chemicals from their structure, while reducing time, cost and animal testing currently needed. Therefore, our studies have been focused on evaluation of available (Q)SAR systems for estimating in vivo repeated toxicity on the liver. The results from our preliminary analysis showed the distribution for LogP of the chemicals which have potential to induce liver toxicity was bell-shape and indicating the possibility to estimate liver toxicity of chemicals from their physicochemical property. We have developed (Q)SAR models to in vivo liver toxicity using three commercially available systems (DEREK, ADMEWorks and MultiCASE) as well as combinatorial use of publically available chemoinformatic tools (CDK, MOSS and WEKA). Distinct data-sets of the 28-day repeated dose toxicity test of new and existing chemicals evaluated in Japan were used for model development and performance test. The results that concordances of commercial systems and public tools were almost same which below 70% may suggest currently attainable knowledge of in silico estimation of complex biological process, though it possible to obtain complementary and enhanced performance by combining predictions from different programs. In future, the combinatorial application of in silico and in vitro tests might provide more accurate

  1. Predicted and observed therapeutic dose exceedances of ionizable pharmaceuticals in fish plasma from urban coastal systems.

    PubMed

    Scott, W Casan; Du, Bowen; Haddad, Samuel P; Breed, Christopher S; Saari, Gavin N; Kelly, Martin; Broach, Linda; Chambliss, C Kevin; Brooks, Bryan W

    2016-04-01

    Instream flows of the rapidly urbanizing watersheds and estuaries of the Gulf of Mexico in Texas (USA) are increasingly dominated by reclaimed waters. Though ionizable pharmaceuticals have received increasing attention in freshwaters, many research questions remain unanswered, particularly in tidally influenced urban coastal systems, which experience significant spatiotemporal variability in pH that influences bioavailability and bioaccumulation. The authors coupled fish plasma modeling of therapeutic hazard values with field monitoring of water chemistry variability and pharmaceutical occurrence to examine whether therapeutic hazards to fish existed within these urban coastal ecosystems and whether therapeutic hazards differed within and among coastal locations and seasons. Spatial and temporal fluctuations in pH within study sites altered the probability of encountering pharmaceutical hazards to fish. Significant water quality differences were consistently observed among traditional parameters and pharmaceuticals collected from surface and bottom waters, which are rarely sampled during routine surface water quality assessments. The authors then compared modeling predictions of fish plasma concentrations of pharmaceuticals to measured plasma levels from various field-collected fish species. Diphenhydramine and diltiazem were observed in plasma of multiple species, and diltiazem exceeded human therapeutic doses in largemouth bass, catfish, and mullet inhabiting these urban estuaries. Though the present study only examined a small number of target analytes, which represent a microcosm of the exposome of these fish, coastal systems are anticipated to be more strongly influenced by continued urbanization, altered instream flows, and population growth in the future. Unfortunately, aquatic toxicology information for diltiazem and many other pharmaceuticals is not available for marine and estuarine organisms, but such field observations suggest that potential adverse

  2. Plasma Coenzyme Q10 Predicts Lipid-lowering Response to High-Dose Atorvastatin

    PubMed Central

    Pacanowski, Michael A.; Frye, Reginald F.; Enogieru, Osatohanmen; Schofield, Richard S.; Zineh, Issam

    2008-01-01

    Background Coenzyme Q10 (CoQ10) is a provitamin synthesized via the HMG-CoA reductase pathway, and thus may serve as a potential marker of intrinsic HMG-CoA reductase activity. HMG-CoA reductase inhibitors (statins) decrease CoQ10, although it is unclear whether this is due to reductions in lipoproteins, which transport CoQ10. Objectives We evaluated whether baseline plasma CoQ10 concentrations predict the lipid-lowering response to high-dose atorvastatin, and to what extent CoQ10 changes following atorvastatin therapy depend on lipoprotein changes. Methods Individuals without dyslipidemia or known cardiovascular disease (n=84) received atorvastatin 80 mg daily for 16 weeks. Blood samples collected at baseline and after 4, 8, and 16 weeks of treatment were assayed for CoQ10. Results Individuals with higher baseline CoQ10:LDL-C ratios displayed diminished absolute and percent LDL-C reductions at 8 and 16 weeks of atorvastatin treatment (P<0.001 to 0.01). After 16 weeks of atorvastatin, plasma CoQ10 decreased 45% from 762±301 ng/ml to 374±150 ng/ml (P<0.001). CoQ10 changes were correlated with LDL-C and apolipoprotein B changes (r=0.27-0.38, P=0.001-0.02), but remained significant when normalized to all lipoproteins. CoQ10 changes were not associated with adverse drug reactions. Conclusion Baseline CoQ10:LDL-C ratio was associated with the degree of LDL-C response to atorvastatin. Atorvastatin decreased CoQ10 concentrations in a manner that was not completely dependent on lipoprotein changes. The utility of CoQ10 as a predictor of atorvastatin response should be further explored in patients with dyslipidemia. PMID:19649137

  3. Incorporating single-side sparing in models for predicting parotid dose sparing in head and neck IMRT

    SciTech Connect

    Yuan, Lulin Wu, Q. Jackie; Yin, Fang-Fang; Yoo, David; Jiang, Yuliang; Ge, Yaorong

    2014-02-15

    Purpose: Sparing of single-side parotid gland is a common practice in head-and-neck (HN) intensity modulated radiation therapy (IMRT) planning. It is a special case of dose sparing tradeoff between different organs-at-risk. The authors describe an improved mathematical model for predicting achievable dose sparing in parotid glands in HN IMRT planning that incorporates single-side sparing considerations based on patient anatomy and learning from prior plan data. Methods: Among 68 HN cases analyzed retrospectively, 35 cases had physician prescribed single-side parotid sparing preferences. The single-side sparing model was trained with cases which had single-side sparing preferences, while the standard model was trained with the remainder of cases. A receiver operating characteristics (ROC) analysis was performed to determine the best criterion that separates the two case groups using the physician's single-side sparing prescription as ground truth. The final predictive model (combined model) takes into account the single-side sparing by switching between the standard and single-side sparing models according to the single-side sparing criterion. The models were tested with 20 additional cases. The significance of the improvement of prediction accuracy by the combined model over the standard model was evaluated using the Wilcoxon rank-sum test. Results: Using the ROC analysis, the best single-side sparing criterion is (1) the predicted median dose of one parotid is higher than 24 Gy; and (2) that of the other is higher than 7 Gy. This criterion gives a true positive rate of 0.82 and a false positive rate of 0.19, respectively. For the bilateral sparing cases, the combined and the standard models performed equally well, with the median of the prediction errors for parotid median dose being 0.34 Gy by both models (p = 0.81). For the single-side sparing cases, the standard model overestimates the median dose by 7.8 Gy on average, while the predictions by the combined

  4. Prediction of terrestrial gamma dose rate based on geological formations and soil types in the Johor State, Malaysia.

    PubMed

    Saleh, Muneer Aziz; Ramli, Ahmad Termizi; bin Hamzah, Khaidzir; Alajerami, Yasser; Moharib, Mohammed; Saeed, Ismael

    2015-10-01

    This study aims to predict and estimate unmeasured terrestrial gamma dose rate (TGDR) using statistical analysis methods to derive a model from the actual measurement based on geological formation and soil type. The measurements of TGDR were conducted in the state of Johor with a total of 3873 measured points which covered all geological formations, soil types and districts. The measurements were taken 1 m above the soil surface using NaI [Ti] detector. The measured gamma dose rates ranged from 9 nGy h(-1) to 1237 nGy h(-1) with a mean value of 151 nGy h(-1). The data have been normalized to fit a normal distribution. Tests of significance were conducted among all geological formations and soil types, using the unbalanced one way ANOVA. The results indicated strong significant differences due to the different geological formations and soil types present in Johor State. Pearson Correlation was used to measure the relations between gamma dose rate based on geological formation and soil type (D(G,S)) with the gamma dose rate based on geological formation (D(G)) or soil type (D(s)). A very good correlation was found between D(G,S) and D(G) or D(G,S) and D(s). A total of 118 pairs of geological formations and soil types were used to derive the statistical contribution of geological formations and soil types to gamma dose rates. The contribution of the gamma dose rate from geological formation and soil type were found to be 0.594 and 0.399, respectively. The null hypotheses were accepted for 83% of examined data, therefore, the model could be used to predict gamma dose rates based on geological formation and soil type information.

  5. Prediction of lethal/effective concentration/dose in the presence of multiple auxiliary covariates and components of variance

    USGS Publications Warehouse

    Gutreuter, S.; Boogaard, M.A.

    2007-01-01

    Predictors of the percentile lethal/effective concentration/dose are commonly used measures of efficacy and toxicity. Typically such quantal-response predictors (e.g., the exposure required to kill 50% of some population) are estimated from simple bioassays wherein organisms are exposed to a gradient of several concentrations of a single agent. The toxicity of an agent may be influenced by auxiliary covariates, however, and more complicated experimental designs may introduce multiple variance components. Prediction methods lag examples of those cases. A conventional two-stage approach consists of multiple bivariate predictions of, say, medial lethal concentration followed by regression of those predictions on the auxiliary covariates. We propose a more effective and parsimonious class of generalized nonlinear mixed-effects models for prediction of lethal/effective dose/concentration from auxiliary covariates. We demonstrate examples using data from a study regarding the effects of pH and additions of variable quantities 2???,5???-dichloro-4???- nitrosalicylanilide (niclosamide) on the toxicity of 3-trifluoromethyl-4- nitrophenol to larval sea lamprey (Petromyzon marinus). The new models yielded unbiased predictions and root-mean-squared errors (RMSEs) of prediction for the exposure required to kill 50 and 99.9% of some population that were 29 to 82% smaller, respectively, than those from the conventional two-stage procedure. The model class is flexible and easily implemented using commonly available software. ?? 2007 SETAC.

  6. PREDICTION OF OUTCOME IN SCHIZOPHRENIA USING THE SUBJECTIVE RESPONSE TO A TEST DOSE OF A NEUROLEPTIC

    PubMed Central

    Borde, Milind; Davis, Elizabeth J.B.; Sharma, L.N.

    1991-01-01

    SUMMARY Twenty four patients meeting R.D.C. criteria for schizophrenia were assessed using the B.P.R.S. before starting neuroleptics. They were then given a standardized test dose of haloperidol. Their subjective response to the test dose was assessed 4 hours later by a blind rater. The B.P.R.S. ratings were repeated after 3 weeks of neuroleptic treatment. A dysphoric response to the test dose was associated with a poor therapeutic outcome. The implications of these findings are discussed. PMID:21897458

  7. Are phantoms useful for predicting the potential of dose reduction in full-field digital mammography?

    NASA Astrophysics Data System (ADS)

    Gennaro, Gisella; Katz, Luc; Souchay, Henri; Alberelli, Claudio; di Maggio, Cosimo

    2005-04-01

    A phantom study was performed in full-field digital mammography to investigate the opportunity and the magnitude of a possible dose reduction that would leave the image quality above the accepted thresholds associated with some classical phantoms. This preliminary work is intended to lay the groundwork for a future clinical study on the impact of dose reduction on clinical results. Three different mammography phantoms (ACR RMI 156, CIRS 11A and CDMAM 3.4) were imaged by a full-field digital mammography unit (GE Senographe 2000D) at different dose levels. Images were rated by three observers with softcopy reading and scoring methods specific to each phantom. Different types of data analysis were applied to the ACR (American College of Radiology) and the other two phantoms, respectively. With reference to the minimum acceptance score in screen/film accreditation programmes, the ACR phantom showed that about 45% dose reduction could be applied, while keeping the phantom scores above that threshold. A relative comparison was done for CIRS and CDMAM, for which no threshold is defined. CIRS scoring remained close to the reference level down to 40% dose reduction, the inter- and intra-observer variability being the main source of uncertainty. Contrast-detail curves provided by CDMAM overlapped down to 50% dose reduction, at least for object contrast values ranging between 30% and 3%. This multi-phantom study shows the potential of further reducing the dose in full-field digital mammography beyond the current values. A common dose reduction factor around 50% seems acceptable for all phantoms. However, caution is required before extrapolating the results for clinical use, given the limitations of these widely used phantoms, mainly related to their limited dynamic range and uniform background.

  8. Dose-Volume Parameters Predict for the Development of Chest Wall Pain After Stereotactic Body Radiation for Lung Cancer

    SciTech Connect

    Mutter, Robert W.; Liu Fan; Abreu, Andres; Yorke, Ellen; Jackson, Andrew; Rosenzweig, Kenneth E.

    2012-04-01

    Purpose: Chest wall (CW) pain has recently been recognized as an important adverse effect of stereotactic body radiation therapy (SBRT) for non-small-cell lung cancer (NSCLC). We developed a dose-volume model to predict the development of this toxicity. Methods and Materials: A total of 126 patients with primary, clinically node-negative NSCLC received three to five fractions of SBRT to doses of 40-60 Gy and were prospectively followed. The dose-absolute volume histograms of two different definitions of the CW as an organ at risk (CW3cm and CW2cm) were examined for all 126 patients. Results: With a median follow-up of 16 months, the 2-year estimated actuarial incidence of Grade {>=} 2 CW pain was 39%. The median time to onset of Grade {>=} 2 CW pain (National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0) was 9 months. There was no predictive advantage for biologically corrected dose over physical dose. Neither fraction number (p = 0.07) nor prescription dose (p = 0.07) were significantly correlated with the development of Grade {>=} 2 CW pain. Cox Proportional Hazards analysis identified significant correlation with a broad range of dose-volume combinations, with the CW volume receiving 30 Gy (V30) as one of the strongest predictors (p < 0.001). CW2cm consistently enabled better prediction of CW toxicity. When a physical dose of 30 Gy was received by more than 70 cm{sup 3} of CW2cm, there was a significant correlation with Grade {>=} 2 CW pain (p = 0.004). Conclusions: CW toxicity after SBRT is common and long-term follow-up is needed to identify affected patients. A volume of CW {>=} 70 cm{sup 3} receiving 30 Gy is significantly correlated with Grade {>=} 2 CW pain. We are currently applying this constraint at our institution for patients receiving thoracic SBRT. An actuarial atlas of our data is provided as an electronic supplement to facilitate data-sharing and meta-analysis relating to CW pain.

  9. The Impact of Genetic and Non-Genetic Factors on Warfarin Dose Prediction in MENA Region: A Systematic Review

    PubMed Central

    2016-01-01

    Background Warfarin is the most commonly used oral anticoagulant for the treatment and prevention of thromboembolic disorders. Pharmacogenomics studies have shown that variants in CYP2C9 and VKORC1 genes are strongly and consistently associated with warfarin dose variability. Although different populations from the Middle East and North Africa (MENA) region may share the same ancestry, it is still unclear how they compare in the genetic and non-genetic factors affecting their warfarin dosing. Objective To explore the prevalence of CYP2C9 and VKORC1 variants in MENA, and the effect of these variants along with other non-genetic factors in predicting warfarin dose. Methods In this systematic review, we included observational cross sectional and cohort studies that enrolled patients on stable warfarin dose and had the genetics and non-genetics factors associated with mean warfarin dose as the primary outcome. We searched PubMed, Medline, Scopus, PharmGKB, PHGKB, Google scholar and reference lists of relevant reviews. Results We identified 17 studies in eight different populations: Iranian, Israeli, Egyptian, Lebanese, Omani, Kuwaiti, Sudanese and Turkish. Most common genetic variant in all populations was the VKORC1 (-1639G>A), with a minor allele frequency ranging from 30% in Egyptians and up to 52% and 56% in Lebanese and Iranian, respectively. Variants in the CYP2C9 were less common, with the highest MAF for CYP2C9*2 among Iranians (27%). Variants in the VKORC1 and CYP2C9 were the most significant predictors of warfarin dose in all populations. Along with other genetic and non-genetic factors, they explained up to 63% of the dose variability in Omani and Israeli patients. Conclusion Variants of VKORC1 and CYP2C9 are the strongest predictors of warfarin dose variability among the different populations from MENA. Although many of those populations share the same ancestry and are similar in their warfarin dose predictors, a population specific dosing algorithm is

  10. Early COPD patients with lung hyperinflation associated with poorer lung function but better bronchodilator responsiveness

    PubMed Central

    Chen, Chunlan; Jian, Wenhua; Gao, Yi; Xie, Yanqing; Song, Yan; Zheng, Jinping

    2016-01-01

    Background It is unknown whether aggressive medication strategies should be used for early COPD with or without lung hyperinflation. We aimed to explore the characteristics and bronchodilator responsiveness of early COPD patients (stages I and II) with/without lung hyperinflation. Methods Four hundred and six patients with COPD who performed both lung volume and bronchodilation tests were retrospectively analyzed. Residual volume to total lung capacity >120% of predicted values indicated lung hyperinflation. The characteristics and bronchodilator responsiveness were compared between the patients with and without lung hyperinflation across all stages of COPD. Results The percentages of patients with lung hyperinflation were 72.7% in the entire cohort, 19.4% in stage I, 68.5% in stage II, 95.3% in stage III, and 100.0% in stage IV. The patients with lung hyperinflation exhibited poorer lung function but better bronchodilator responsiveness of both forced expiratory volume in 1 second and forced vital capacity than those without lung hyperinflation during early COPD (t=2.21–5.70, P=0.000–0.029), especially in stage I, while age, body mass index, smoking status, smoking history, and disease duration were similar between the two subgroups in the same stages. From stages I to IV of subgroups with lung hyperinflation, stage I patients had the best bronchodilator responsiveness. Use of bronchodilator responsiveness of forced vital capacity to detect the presence of lung hyperinflation in COPD patients showed relatively high sensitivities (69.5%–75.3%) and specificities (70.3%–75.7%). Conclusion We demonstrated the novel finding that early COPD patients with lung hyperinflation are associated with poorer lung function but better bronchodilator responsiveness and established a simple method for detecting lung hyperinflation. PMID:27785008

  11. Development of a novel individualized warfarin dose algorithm based on a population pharmacokinetic model with improved prediction accuracy for Chinese patients after heart valve replacement

    PubMed Central

    Zhu, Yu-bin; Hong, Xian-hua; Wei, Meng; Hu, Jing; Chen, Xin; Wang, Shu-kui; Zhu, Jun-rong; Yu, Feng; Sun, Jian-guo

    2017-01-01

    The gene-guided dosing strategy of warfarin generally leads to over-dose in patients at doses lower than 2 mg/kg, and only 50% of individual variability in daily stable doses can be explained. In this study, we developed a novel population pharmacokinetic (PK) model based on a warfarin dose algorithm for Han Chinese patients with valve replacement for improving the dose prediction accuracy, especially in patients with low doses. The individual pharmacokinetic (PK) parameter - apparent clearance of S- and R-warfarin (CLs) was obtained after establishing and validating the population PK model from 296 recruited patients with valve replacement. Then, the individual estimation of CLs, VKORC1 genotypes, the steady-state international normalized ratio (INR) values and age were used to describe the maintenance doses by multiple linear regression for 144 steady-state patients. The newly established dosing algorithm was then validated in an independent group of 42 patients and was compared with other dosing algorithms for the accuracy and precision of prediction. The final regression model developed was as follows: Dose=-0.023×AGE+1.834×VKORC1+0.952×INR+2.156×CLs (the target INR value ranges from 1.8 to 2.5). The validation of the algorithm in another group of 42 patients showed that the individual variation rate (71.6%) was higher than in the gene-guided dosing models. The over-estimation rate in patients with low doses (<2 mg/kg) was lower than the other dosing methods. This novel dosing algorithm based on a population PK model improves the predictive performance of the maintenance dose of warfarin, especially for low dose (<2 mg/d) patients. PMID:28216623

  12. Mixed-effects Gaussian process functional regression models with application to dose-response curve prediction.

    PubMed

    Shi, J Q; Wang, B; Will, E J; West, R M

    2012-11-20

    We propose a new semiparametric model for functional regression analysis, combining a parametric mixed-effects model with a nonparametric Gaussian process regression model, namely a mixed-effects Gaussian process functional regression model. The parametric component can provide explanatory information between the response and the covariates, whereas the nonparametric component can add nonlinearity. We can model the mean and covariance structures simultaneously, combining the information borrowed from other subjects with the information collected from each individual subject. We apply the model to dose-response curves that describe changes in the responses of subjects for differing levels of the dose of a drug or agent and have a wide application in many areas. We illustrate the method for the management of renal anaemia. An individual dose-response curve is improved when more information is included by this mechanism from the subject/patient over time, enabling a patient-specific treatment regime.

  13. Aging and sequential modulations of poorer strategy effects: An EEG study in arithmetic problem solving.

    PubMed

    Hinault, Thomas; Lemaire, Patrick; Phillips, Natalie

    2016-01-01

    This study investigated age-related differences in electrophysiological signatures of sequential modulations of poorer strategy effects. Sequential modulations of poorer strategy effects refer to decreased poorer strategy effects (i.e., poorer performance when the cued strategy is not the best) on current problem following poorer strategy problems compared to after better strategy problems. Analyses on electrophysiological (EEG) data revealed important age-related changes in time, frequency, and coherence of brain activities underlying sequential modulations of poorer strategy effects. More specifically, sequential modulations of poorer strategy effects were associated with earlier and later time windows (i.e., between 200- and 550 ms and between 850- and 1250 ms). Event-related potentials (ERPs) also revealed an earlier onset in older adults, together with more anterior and less lateralized activations. Furthermore, sequential modulations of poorer strategy effects were associated with theta and alpha frequencies in young adults while these modulations were found in delta frequency and theta inter-hemispheric coherence in older adults, consistent with qualitatively distinct patterns of brain activity. These findings have important implications to further our understanding of age-related differences and similarities in sequential modulations of cognitive control processes during arithmetic strategy execution.

  14. A New Drug Combinatory Effect Prediction Algorithm on the Cancer Cell Based on Gene Expression and Dose-Response Curve.

    PubMed

    Goswami, C Pankaj; Cheng, L; Alexander, P S; Singal, A; Li, L

    2015-02-01

    Gene expression data before and after treatment with an individual drug and the IC20 of dose-response data were utilized to predict two drugs' interaction effects on a diffuse large B-cell lymphoma (DLBCL) cancer cell. A novel drug interaction scoring algorithm was developed to account for either synergistic or antagonistic effects between drug combinations. Different core gene selection schemes were investigated, which included the whole gene set, the drug-sensitive gene set, the drug-sensitive minus drug-resistant gene set, and the known drug target gene set. The prediction scores were compared with the observed drug interaction data at 6, 12, and 24 hours with a probability concordance (PC) index. The test result shows the concordance between observed and predicted drug interaction ranking reaches a PC index of 0.605. The scoring reliability and efficiency was further confirmed in five drug interaction studies published in the GEO database.

  15. Poorer verbal working memory for a second language selectively impacts academic achievement in university medical students.

    PubMed

    Mann, Collette; Canny, Benedict J; Reser, David H; Rajan, Ramesh

    2013-01-01

    Working memory (WM) is often poorer for a second language (L2). In low noise conditions, people listening to a language other than their first language (L1) may have similar auditory perception skills for that L2 as native listeners, but do worse in high noise conditions, and this has been attributed to the poorer WM for L2. Given that WM is critical for academic success in children and young adults, these speech in noise effects have implications for academic performance where the language of instruction is L2 for a student. We used a well-established Speech-in-Noise task as a verbal WM (vWM) test, and developed a model correlating vWM and measures of English proficiency and/or usage to scholastic outcomes in a multi-faceted assessment medical education program. Significant differences in Speech-Noise Ratio (SNR50) values were observed between medical undergraduates who had learned English before or after five years of age, with the latter group doing worse in the ability to extract whole connected speech in the presence of background multi-talker babble (Student-t tests, p < 0.001). Significant negative correlations were observed between the SNR50 and seven of the nine variables of English usage, learning styles, stress, and musical abilities in a questionnaire administered to the students previously. The remaining two variables, Perceived Stress Scale (PSS) and the Age of Acquisition of English (AoAoE) were significantly positively correlated with the SNR50, showing that those with a poorer capacity to discriminate simple English sentences from noise had learnt English later in life and had higher levels of stress - all characteristics of the international students. Local students exhibited significantly lower SNR50 scores and were significantly younger when they first learnt English. No significant correlation was detected between the SNR50 and the students' Visual/Verbal Learning Style (r = -0.023). Standard multiple regression was carried out to assess

  16. Poorer verbal working memory for a second language selectively impacts academic achievement in university medical students

    PubMed Central

    Canny, Benedict J.; Reser, David H.; Rajan, Ramesh

    2013-01-01

    Working memory (WM) is often poorer for a second language (L2). In low noise conditions, people listening to a language other than their first language (L1) may have similar auditory perception skills for that L2 as native listeners, but do worse in high noise conditions, and this has been attributed to the poorer WM for L2. Given that WM is critical for academic success in children and young adults, these speech in noise effects have implications for academic performance where the language of instruction is L2 for a student. We used a well-established Speech-in-Noise task as a verbal WM (vWM) test, and developed a model correlating vWM and measures of English proficiency and/or usage to scholastic outcomes in a multi-faceted assessment medical education program. Significant differences in Speech-Noise Ratio (SNR50 ) values were observed between medical undergraduates who had learned English before or after five years of age, with the latter group doing worse in the ability to extract whole connected speech in the presence of background multi-talker babble (Student-t tests, p < 0.001). Significant negative correlations were observed between the SNR50 and seven of the nine variables of English usage, learning styles, stress, and musical abilities in a questionnaire administered to the students previously. The remaining two variables, Perceived Stress Scale (PSS) and the Age of Acquisition of English (AoAoE) were significantly positively correlated with the SNR50 , showing that those with a poorer capacity to discriminate simple English sentences from noise had learnt English later in life and had higher levels of stress – all characteristics of the international students. Local students exhibited significantly lower SNR50 scores and were significantly younger when they first learnt English. No significant correlation was detected between the SNR50 and the students’ Visual/Verbal Learning Style (r = −0.023). Standard multiple regression was carried out to

  17. Prediction of the location and size of the stomach using patient characteristics for retrospective radiation dose estimation following radiotherapy.

    PubMed

    Lamart, Stephanie; Imran, Rebecca; Simon, Steven L; Doi, Kazutaka; Morton, Lindsay M; Curtis, Rochelle E; Lee, Choonik; Drozdovitch, Vladimir; Maass-Moreno, Roberto; Chen, Clara C; Whatley, Millie; Miller, Donald L; Pacak, Karel; Lee, Choonsik

    2013-12-21

    Following cancer radiotherapy, reconstruction of doses to organs, other than the target organ, is of interest for retrospective health risk studies. Reliable estimation of doses to organs that may be partially within or fully outside the treatment field requires reliable knowledge of the location and size of the organs, e.g., the stomach, which is at risk from abdominal irradiation. The stomach location and size are known to be highly variable between individuals, but have been little studied. Moreover, for treatments conducted years ago, medical images of patients are usually not available in medical records to locate the stomach. In light of the poor information available to locate the stomach in historical dose reconstructions, the purpose of this work was to investigate the variability of stomach location and size among adult male patients and to develop prediction models for the stomach location and size using predictor variables generally available in medical records of radiotherapy patients treated in the past. To collect data on stomach size and position, we segmented the contours of the stomach and of the skeleton on contemporary computed tomography (CT) images for 30 male patients in supine position. The location and size of the stomach was found to depend on body mass index (BMI), ponderal index (PI), and age. For example, the anteroposterior dimension of the stomach was found to increase with increasing BMI (≈0.25 cm kg(-1) m(2)) whereas its craniocaudal dimension decreased with increasing PI (≈-3.3 cm kg(-1) m(3)) and its transverse dimension increased with increasing PI (≈2.5 cm kg(-1) m(3)). Using the prediction models, we generated three-dimensional computational stomach models from a deformable hybrid phantom for three patients of different BMI. Based on a typical radiotherapy treatment, we simulated radiotherapy treatments on the predicted stomach models and on the CT images of the corresponding patients. Those dose calculations demonstrated

  18. Prediction of the location and size of the stomach using patient characteristics for retrospective radiation dose estimation following radiotherapy

    NASA Astrophysics Data System (ADS)

    Lamart, Stephanie; Imran, Rebecca; Simon, Steven L.; Doi, Kazutaka; Morton, Lindsay M.; Curtis, Rochelle E.; Lee, Choonik; Drozdovitch, Vladimir; Maass-Moreno, Roberto; Chen, Clara C.; Whatley, Millie; Miller, Donald L.; Pacak, Karel; Lee, Choonsik

    2013-12-01

    Following cancer radiotherapy, reconstruction of doses to organs, other than the target organ, is of interest for retrospective health risk studies. Reliable estimation of doses to organs that may be partially within or fully outside the treatment field requires reliable knowledge of the location and size of the organs, e.g., the stomach, which is at risk from abdominal irradiation. The stomach location and size are known to be highly variable between individuals, but have been little studied. Moreover, for treatments conducted years ago, medical images of patients are usually not available in medical records to locate the stomach. In light of the poor information available to locate the stomach in historical dose reconstructions, the purpose of this work was to investigate the variability of stomach location and size among adult male patients and to develop prediction models for the stomach location and size using predictor variables generally available in medical records of radiotherapy patients treated in the past. To collect data on stomach size and position, we segmented the contours of the stomach and of the skeleton on contemporary computed tomography (CT) images for 30 male patients in supine position. The location and size of the stomach was found to depend on body mass index (BMI), ponderal index (PI), and age. For example, the anteroposterior dimension of the stomach was found to increase with increasing BMI (≈0.25 cm kg-1 m2) whereas its craniocaudal dimension decreased with increasing PI (≈-3.3 cm kg-1 m3) and its transverse dimension increased with increasing PI (≈2.5 cm kg-1 m3). Using the prediction models, we generated three-dimensional computational stomach models from a deformable hybrid phantom for three patients of different BMI. Based on a typical radiotherapy treatment, we simulated radiotherapy treatments on the predicted stomach models and on the CT images of the corresponding patients. Those dose calculations demonstrated good

  19. The calculation of radial dose from heavy ions: predictions of biological action cross sections

    NASA Technical Reports Server (NTRS)

    Katz, R.; Cucinotta, F. A.; Zhang, C. X.; Wilson, J. W. (Principal Investigator)

    1996-01-01

    The track structure model of heavy ion cross sections was developed by Katz and co-workers in the 1960s. In this model the action cross section is evaluated by mapping the dose-response of a detector to gamma rays (modeled from biological target theory) onto the radial dose distribution from delta rays about the path of the ion. This is taken to yield the radial distribution of probability for a "hit" (an interaction leading to an observable end-point). Radial integration of the probability yields the cross section. When different response from ions of different Z having the same stopping power is observed this model may be indicated. Since the 1960s there have been several developments in the computation of the radial dose distribution, in the measurement of these distributions, and in new radiobiological data against which to test the model. The earliest model, by Butts and Katz made use of simplified delta ray distribution functions, of simplified electron range-energy relations, and neglected angular distributions. Nevertheless it made possible the calculation of cross sections for the inactivation of enzymes and viruses, and allowed extension to tracks in nuclear emulsions and other detectors and to biological cells. It set the pattern for models of observable effects in the matter through which the ion passed. Here we outline subsequent calculations of radial dose which make use of improved knowledge of the electron emission spectrum, the electron range-energy relation, the angular distribution, and some considerations of molecular excitation, of particular interest both close to the path of the ion and the outer limits of electron penetration. These are applied to the modeling of action cross sections for the inactivation of several strains of E-coli and B. subtilis spores where extensive measurements in the "thin-down" region have been made with heavy ion beams. Such calculations serve to test the radial dose calculations at the outer limit of electron

  20. Multivariate analysis of factors predicting prostate dose in intensity-modulated radiotherapy

    SciTech Connect

    Tomita, Tsuneyuki; Nakamura, Mitsuhiro; Hirose, Yoshinori; Kitsuda, Kenji; Notogawa, Takuya; Miki, Katsuhito; Nakamura, Kiyonao; Ishigaki, Takashi

    2014-01-01

    We conducted a multivariate analysis to determine relationships between prostate radiation dose and the state of surrounding organs, including organ volumes and the internal angle of the levator ani muscle (LAM), based on cone-beam computed tomography (CBCT) images after bone matching. We analyzed 270 CBCT data sets from 30 consecutive patients receiving intensity-modulated radiation therapy for prostate cancer. With patients in the supine position on a couch with the HipFix system, data for center of mass (COM) displacement of the prostate and the state of individual organs were acquired and compared between planning CT and CBCT scans. Dose distributions were then recalculated based on CBCT images. The relative effects of factors on the variance in COM, dose covering 95% of the prostate volume (D{sub 95%}), and percentage of prostate volume covered by the 100% isodose line (V{sub 100%}) were evaluated by a backward stepwise multiple regression analysis. COM displacement in the anterior-posterior direction (COM{sub AP}) correlated significantly with the rectum volume (δVr) and the internal LAM angle (δθ; R = 0.63). Weak correlations were seen for COM in the left-right (R = 0.18) and superior-inferior directions (R = 0.31). Strong correlations between COM{sub AP} and prostate D{sub 95%} and V{sub 100%} were observed (R ≥ 0.69). Additionally, the change ratios in δVr and δθ remained as predictors of prostate D{sub 95%} and V{sub 100%}. This study shows statistically that maintaining the same rectum volume and LAM state for both the planning CT simulation and treatment is important to ensure the correct prostate dose in the supine position with bone matching.

  1. Potential of a Pharmacogenetic-Guided Algorithm to Predict Optimal Warfarin Dosing in a High-Risk Hispanic Patient

    PubMed Central

    Hernandez-Suarez, Dagmar F.; Claudio-Campos, Karla; Mirabal-Arroyo, Javier E.; Torres-Hernández, Bianca A.; López-Candales, Angel; Melin, Kyle; Duconge, Jorge

    2016-01-01

    Deep abdominal vein thrombosis is extremely rare among thrombotic events secondary to the use of contraceptives. A case to illustrate the clinical utility of ethno-specific pharmacogenetic testing in warfarin management of a Hispanic patient is reported. A 37-year-old Hispanic Puerto Rican, non-gravid female with past medical history of abnormal uterine bleeding on hormonal contraceptive therapy was evaluated for abdominal pain. Physical exam was remarkable for unspecific diffuse abdominal tenderness, and general initial laboratory results—including coagulation parameters—were unremarkable. A contrast-enhanced computed tomography showed a massive thrombosis of the main portal, splenic, and superior mesenteric veins. On admission the patient was started on oral anticoagulation therapy with warfarin at 5 mg/day and low-molecular-weight heparin. The prediction of an effective warfarin dose of 7.5 mg/day, estimated by using a recently developed pharmacogenetic-guided algorithm for Caribbean Hispanics, coincided with the actual patient’s warfarin dose to reach the international normalized ratio target. We speculate that the slow rise in patient’s international normalized ratio observed on the initiation of warfarin therapy, the resulting high risk for thromboembolic events, and the required warfarin dose of 7.5 mg/day are attributable in some part to the presence of the NQO1*2 (g.559C>T, p.P187S) polymorphism, which seems to be significantly associated with resistance to warfarin in Hispanics. By adding genotyping results of this novel variant, the predictive model can inform clinicians better about the optimal warfarin dose in Caribbean Hispanics. The results highlight the potential for pharmacogenetic testing of warfarin to improve patient care. PMID:28210634

  2. Stereotactic Body Radiotherapy for Patients With Unresectable Primary Hepatocellular Carcinoma: Dose-Volumetric Parameters Predicting the Hepatic Complication

    SciTech Connect

    Son, Seok Hyun; Choi, Byung Ock; Ryu, Mi Ryeong; Kang, Young Nam; Jang, Ji Sun; Bae, Si Hyun; Yoon, Seung Kew; Choi, Ihl Bohng; Kang, Ki Mun; Jang, Hong Seok

    2010-11-15

    Purpose: To identify the parameters that predict hepatic toxicity and deterioration of hepatic function. Materials and Methods: A total of 47 patients with small unresectable primary hepatocellular carcinoma received hypofractionated stereotactic body radiotherapy (SBRT) using the CyberKnife. Of those, 36 patients received no other local treatments that could influence hepatic toxicity at least for 3 months after the completion of SBRT. The gross tumor volume (GTV) was 18.3 {+-} 15.9 cm{sup 3} (range, 3.0-81.3 cm{sup 3}), and the total dose administered was 30-39 Gy (median, 36 Gy). To assess the deterioration of hepatic function, we evaluated the presence or absence of the progression of Child-Pugh class (CP class). To identify the parameters of predicting the radiation-induced hepatic toxicity and deterioration of the hepatic function, several clinical and dose-volumetric parameters were evaluated. Results: Of 36 patients, 12 (33%) developed Grade 2 or higher hepatic toxicity and 4 (11%) developed progression of CP class. The multivariate analysis showed that the only significant parameter associated with the progression of CP class was the total liver volume receiving a dose less than 18 Gy (<18 Gy). Conclusions: The progression of CP class after SBRT limits other additional local treatments and also reflects the deterioration of hepatic function. Therefore, it would be important to note that the presence or absence of the progression of CP class is a dose-limiting factor. The total liver volume receiving <18 Gy should be greater than 800 cm{sup 3} to reduce the risk of the deterioration of hepatic function.

  3. SU-F-BRB-10: A Statistical Voxel Based Normal Organ Dose Prediction Model for Coplanar and Non-Coplanar Prostate Radiotherapy

    SciTech Connect

    Tran, A; Yu, V; Nguyen, D; Woods, K; Low, D; Sheng, K

    2015-06-15

    Purpose: Knowledge learned from previous plans can be used to guide future treatment planning. Existing knowledge-based treatment planning methods study the correlation between organ geometry and dose volume histogram (DVH), which is a lossy representation of the complete dose distribution. A statistical voxel dose learning (SVDL) model was developed that includes the complete dose volume information. Its accuracy of predicting volumetric-modulated arc therapy (VMAT) and non-coplanar 4π radiotherapy was quantified. SVDL provided more isotropic dose gradients and may improve knowledge-based planning. Methods: 12 prostate SBRT patients originally treated using two full-arc VMAT techniques were re-planned with 4π using 20 intensity-modulated non-coplanar fields to a prescription dose of 40 Gy. The bladder and rectum voxels were binned based on their distances to the PTV. The dose distribution in each bin was resampled by convolving to a Gaussian kernel, resulting in 1000 data points in each bin that predicted the statistical dose information of a voxel with unknown dose in a new patient without triaging information that may be collectively important to a particular patient. We used this method to predict the DVHs, mean and max doses in a leave-one-out cross validation (LOOCV) test and compared its performance against lossy estimators including mean, median, mode, Poisson and Rayleigh of the voxelized dose distributions. Results: SVDL predicted the bladder and rectum doses more accurately than other estimators, giving mean percentile errors ranging from 13.35–19.46%, 4.81–19.47%, 22.49–28.69%, 23.35–30.5%, 21.05–53.93% for predicting mean, max dose, V20, V35, and V40 respectively, to OARs in both planning techniques. The prediction errors were generally lower for 4π than VMAT. Conclusion: By employing all dose volume information in the SVDL model, the OAR doses were more accurately predicted. 4π plans are better suited for knowledge-based planning than

  4. Aging effects in sequential modulations of poorer-strategy effects during execution of memory strategies.

    PubMed

    Hinault, Thomas; Lemaire, Patrick; Touron, Dayna

    2017-02-01

    In this study, we asked young adults and older adults to encode pairs of words. For each item, they were told which strategy to use, interactive imagery or rote repetition. Data revealed poorer-strategy effects in both young adults and older adults: Participants obtained better performance when executing better strategies (i.e., interactive-imagery strategy to encode pairs of concrete words; rote-repetition strategy on pairs of abstract words) than with poorer strategies (i.e., interactive-imagery strategy on pairs of abstract words; rote-repetition strategy on pairs of concrete words). Crucially, we showed that sequential modulations of poorer-strategy effects (i.e., poorer-strategy effects being larger when previous items were encoded with better relative to poorer strategies), previously demonstrated in arithmetic, generalise to memory strategies. We also found reduced sequential modulations of poorer-strategy effects in older adults relative to young adults. Finally, sequential modulations of poorer-strategy effects correlated with measures of cognitive control processes, suggesting that these processes underlie efficient trial-to-trial modulations during strategy execution. Differences in correlations with cognitive control processes were also found between older adults and young adults. These findings have important implications regarding mechanisms underlying memory strategy execution and age differences in memory performance.

  5. Dose to Larynx Predicts for Swallowing Complications After Intensity-Modulated Radiotherapy

    SciTech Connect

    Caglar, Hale B.; Tishler, Roy B.; Burke, Elaine; Li Yi; Goguen, Laura; Norris, Carl M.; Allen, Aaron M.

    2008-11-15

    Purpose: To evaluate early swallowing after intensity-modulated radiotherapy for head and neck squamous cell carcinoma and determine factors correlating with aspiration and/or stricture. Methods and Materials: Consecutive patients treated with intensity-modulated radiotherapy with or without chemotherapy between September 2004 and August 2006 at the Dana Farber Cancer Institute/Brigham and Women's Hospital were evaluated with institutional review board approval. Patients underwent swallowing evaluation after completion of therapy; including video swallow studies. The clinical- and treatment-related variables were examined for correlation with aspiration or strictures, as well as doses to the larynx, pharyngeal constrictor muscles, and cervical esophagus. The correlation was assessed with logistic regression analysis. Results: A total of 96 patients were evaluated. Their median age was 55 years, and 79 (82%) were men. The primary site of cancer was the oropharynx in 43, hypopharynx/larynx in 17, oral cavity in 13, nasopharynx in 11, maxillary sinus in 2, and unknown primary in 10. Of the 96 patients, 85% underwent definitive RT and 15% postoperative RT. Also, 28 patients underwent induction chemotherapy followed by concurrent chemotherapy, 59 received concurrent chemotherapy, and 9 patients underwent RT alone. The median follow-up was 10 months. Of the 96 patients, 31 (32%) had clinically significant aspiration and 36 (37%) developed a stricture. The radiation dose-volume metrics, including the volume of the larynx receiving {>=}50 Gy (p = 0.04 and p = 0.03, respectively) and volume of the inferior constrictor receiving {>=}50 Gy (p = 0.05 and p = 0.02, respectively) were significantly associated with both aspiration and stricture. The mean larynx dose correlated with aspiration (p = 0.003). Smoking history was the only clinical factor to correlate with stricture (p = 0.05) but not aspiration. Conclusion: Aspiration and stricture are common side effects after

  6. Calculation and Prediction of the Effect of Respiratory Motion on Whole Breast Radiation Therapy Dose Distributions

    SciTech Connect

    Cao Junsheng; Roeske, John C.; Chmura, Steve J.; Salama, Joseph K.; Shoushtari, Asal N.; Boyer, Arthur L.; Martel, Mary K.

    2009-07-01

    The standard treatment technique used for whole-breast irradiation can result in undesirable dose distributions in the treatment site, leading to skin reaction/fibrosis and pulmonary and cardiac toxicities. Hence, the technique has evolved from conventional wedged technique (CWT) to segment intensity-modulated radiation therapy (SIMRT) and beamlet IMRT (IMRT). However, these newer techniques feature more highly modulated dose distributions that may be affected by respiration. The purpose of this work was to conduct a simple study of the clinical impact of respiratory motion on breast radiotherapy dose distributions for the three treatment planning techniques. The ultimate goal was to determine which patients would benefit most from the use of motion management. Eight patients with early-stage breast cancer underwent a free-breathing (FB) computed tomography (CT) simulation, with medial and lateral markers placed on the skin. Two additional CT scans were obtained at the end of inspiration (EI) and the end of expiration (EE). The FB-CT scan was used to develop treatment plans using each technique. Each plan was then applied to EI and EE-CT scans. Compared with the FB CT scan, the medial markers moved up to 1.8 cm in the anterior-superior direction at the end of inspiration (EI-scan), and on average 8 mm. The CWT and SIMRT techniques were not 'sensitive' to respiratory motion, because the % clinical target volume (CTV) receiving 95% of the prescription dose (V{sub 95%}) remained constant for both techniques. For patients that had large respiratory motion indicated by marker movement >0.6 cm, differences in coverage of the CTV at the V100% between FB and EI for beamlet IMRT plans were on the order of >10% and up to 18%. A linear model was developed to relate the dosimetric coverage difference introduced by respiration with the motion information. With this model, the dosimetric coverage difference introduced by respiratory motion could be evaluated during patient CT

  7. Application of PK/PD Modeling in Veterinary Field: Dose Optimization and Drug Resistance Prediction

    PubMed Central

    Ahmad, Ijaz; Huang, Lingli; Hao, Haihong; Sanders, Pascal; Yuan, Zonghui

    2016-01-01

    Among veterinary drugs, antibiotics are frequently used. The true mean of antibiotic treatment is to administer dose of drug that will have enough high possibility of attaining the preferred curative effect, with adequately low chance of concentration associated toxicity. Rising of antibacterial resistance and lack of novel antibiotic is a global crisis; therefore there is an urgent need to overcome this problem. Inappropriate antibiotic selection, group treatment, and suboptimal dosing are mostly responsible for the mentioned problem. One approach to minimizing the antibacterial resistance is to optimize the dosage regimen. PK/PD model is important realm to be used for that purpose from several years. PK/PD model describes the relationship between drug potency, microorganism exposed to drug, and the effect observed. Proper use of the most modern PK/PD modeling approaches in veterinary medicine can optimize the dosage for patient, which in turn reduce toxicity and reduce the emergence of resistance. The aim of this review is to look at the existing state and application of PK/PD in veterinary medicine based on in vitro, in vivo, healthy, and disease model. PMID:26989688

  8. Low energy electron generator design and depth dose prediction for micro-superficies tumors treatment purposes

    NASA Astrophysics Data System (ADS)

    Khorshidi, Abdollah; Rajaee, Azimeh; Ahmadinejad, Marjan; Ghoranneviss, Mahmood; Ettelaee, Mehdi

    2014-09-01

    We investigate deposited energy and linear energy transfer (LET) of low energy ejection electrons in air and water layers of a generator design via a plasma source. A structured model of a concave cold cathode electron generator was designed and simulated by using Monte Carlo n-particle version X 2.7.0 (MCNPX) code. A negative dc high voltage was applied to a concave cathode up to -12 kV to determine electron energy activity. Results determined that the geometric dimensions of field size toward the anode increased in relation to the angle of the conic beam, widening the accumulated bulks. The increased field size increased the anode current, which also resulted in an increase of electron energy, a reduction in LET, a stretched build-up area and a dose curve that shifted to a higher depth. The biological effect of low energy electron radiation can be increased with an increase of LET; as the depth dose decreased, the electron energy increased at the same time. The study of electron irradiation as a conic beam from an electron generator may provide an accurate investigation of the indirect effect of low energy electrons on bystander cells.

  9. Application of PK/PD Modeling in Veterinary Field: Dose Optimization and Drug Resistance Prediction.

    PubMed

    Ahmad, Ijaz; Huang, Lingli; Hao, Haihong; Sanders, Pascal; Yuan, Zonghui

    2016-01-01

    Among veterinary drugs, antibiotics are frequently used. The true mean of antibiotic treatment is to administer dose of drug that will have enough high possibility of attaining the preferred curative effect, with adequately low chance of concentration associated toxicity. Rising of antibacterial resistance and lack of novel antibiotic is a global crisis; therefore there is an urgent need to overcome this problem. Inappropriate antibiotic selection, group treatment, and suboptimal dosing are mostly responsible for the mentioned problem. One approach to minimizing the antibacterial resistance is to optimize the dosage regimen. PK/PD model is important realm to be used for that purpose from several years. PK/PD model describes the relationship between drug potency, microorganism exposed to drug, and the effect observed. Proper use of the most modern PK/PD modeling approaches in veterinary medicine can optimize the dosage for patient, which in turn reduce toxicity and reduce the emergence of resistance. The aim of this review is to look at the existing state and application of PK/PD in veterinary medicine based on in vitro, in vivo, healthy, and disease model.

  10. Clinical dose-volume histogram analysis in predicting radiation pneumonitis in Hodgkin's lymphoma

    SciTech Connect

    Koh, Eng-Siew; Sun, Alexander . E-mail: alex.sun@rmp.uhn.on.ca; Tu Huan Tran; Tsang, Richard; Pintilie, Melania; Hodgson, David C.; Wells, Woodrow; Heaton, Robert; Gospodarowicz, Mary K.

    2006-09-01

    Purpose: To quantify the incidence of radiation pneumonitis (RP) in a modern Hodgkin's lymphoma (HL) cohort, and to identify any clinically relevant parameters that may influence the risk of RP. Methods and Materials: Between January 2003 and February 2005, 64 consecutive HL patients aged 18 years or older receiving radical mediastinal radiation therapy (RT) were retrospectively reviewed. Symptomatic cases of radiation pneumonitis were identified. Dose-volume histogram parameters, including V{sub 13}, V{sub 2}, V{sub 3}, and mean lung dose (MLD), were quantified. Results: At a median follow-up of 2.1 years, the actuarial survival for all patients was 91% at 3 years. There were 2 (2/64) cases of Radiation Therapy Oncology Group (RTOG) Grade 2 RP (incidence 3.1%). Both index cases with corresponding V{sub 2} values of 47.0% and 40.7% were located in the upper quartile (2/16 cases), defined by a V{sub 2} value of {>=}36%, an incidence of 12.5% (p = 0.03). Similarly for total MLD, both index cases with values of 17.6 Gy and 16.4 Gy, respectively, were located in the upper quartile defined by MLD {>=}14.2 Gy, an incidence of 11.8% (2/17 cases, p = 0.02). Conclusions: Despite relatively high V{sub 2} values in this study of HL patients, the incidence of RP was only 3%, lower compared with the lung cancer literature. We suggest the following clinically relevant parameters be considered in treatment plan assessment: a V{sub 2} greater than 36% and an MLD greater than 14 Gy, over and above which the risk of RTOG Grade 2 or greater RP would be considered clinically significant.

  11. Prediction of powdered activated carbon doses for 2-MIB removal in drinking water treatment using a simplified HSDM approach.

    PubMed

    Yu, Jianwei; Yang, Fong-Chen; Hung, Wei-Nung; Liu, Chia-Ling; Yang, Min; Lin, Tsair-Fuh

    2016-08-01

    The addition of powdered activated carbon (PAC) is an effective measure to cope with seasonal taste and odor (T&O) problems caused by 2-methylisoborneol (2-MIB) and trans-1, 10-dimethyl-trans-9-decalol (geosmin) in drinking water. Some T&O problems are episodic in nature, and generally require rapid responses. This paper proposed a simplified approach for the application of the homogenous surface diffusion model (HSDM) to predict the appropriate PAC doses for the removal of 2-MIB. Equilibrium and kinetic experiments were performed for 2-MIB adsorption onto five PACs in three source waters. The simplified HSDM approach was compared with the experimental data, by assigning the Freundlich 1/n value in the range of 0.1-1.0 and obtaining the Freundlich equilibrium parameter K value through a 6-hr adsorption kinetic test. The model describes the kinetic adsorption data very well for all of the tested PACs in different source waters. The results were validated using the data obtained from one full scale water treatment plant, and the differences between the predicted and observed results were within 10% range. This simplified HSDM approach may be applied for the rapid determination of PAC doses for water treatment plants when faced with 2-MIB episodes in source waters.

  12. Predicting the hazardous dose of industrial chemicals in warm-blooded species using machine learning-based modelling approaches.

    PubMed

    Gupta, S; Basant, N; Singh, K P

    2015-06-01

    The hazardous dose of a chemical (HD50) is an emerging and acceptable test statistic for the safety/risk assessment of chemicals. Since it is derived using the experimental toxicity values of the chemical in several test species, it is highly cumbersome, time and resource intensive. In this study, three machine learning-based QSARs were established for predicting the HD50 of chemicals in warm-blooded species following the OECD guidelines. A data set comprising HD50 values of 957 chemicals was used to develop SDT, DTF and DTB QSAR models. The diversity in chemical structures and nonlinearity in the data were verified. Several validation coefficients were derived to test the predictive and generalization abilities of the constructed QSARs. The chi-path descriptors were identified as the most influential in three QSARs. The DTF and DTB performed relatively better than SDT model and yielded r(2) values of 0.928 and 0.959 between the measured and predicted HD50 values in the complete data set. Substructure alerts responsible for the toxicity of the chemicals were identified. The results suggest the appropriateness of the developed QSARs for reliably predicting the HD50 values of chemicals, and they can be used for screening of new chemicals for their safety/risk assessment for regulatory purposes.

  13. Perineural Invasion Predicts Increased Recurrence, Metastasis, and Death From Prostate Cancer Following Treatment With Dose-Escalated Radiation Therapy

    SciTech Connect

    Feng, Felix Y.; Qian Yushen; Stenmark, Matthew H.; Halverson, Schuyler; Blas, Kevin; Vance, Sean; Sandler, Howard M.; Hamstra, Daniel A.

    2011-11-15

    Purpose: To assess the prognostic value of perineural invasion (PNI) for patients treated with dose-escalated external-beam radiation therapy for prostate cancer. Methods and Materials: Outcomes were analyzed for 651 men treated for prostate cancer with EBRT to a minimum dose {>=}75 Gy. We assessed the impact of PNI as well as pretreatment and treatment-related factors on freedom from biochemical failure (FFBF), freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival. Results: PNI was present in 34% of specimens at biopsy and was significantly associated with higher Gleason score (GS), T stage, and prostate-specific antigen level. On univariate and multivariate analysis, the presence of PNI was associated with worse FFBF (hazard ratio = 1.7, p <0.006), FFM (hazard ratio = 1.8, p <0.03), and CSS (HR = 1.4, p <0.05) compared with absence of PNI; there was no difference in overall survival. Seven-year rates of FFBF, FFM, and CCS were 64% vs. 80%, 84% vs. 92%, and 91% vs. 95% for those patients with and without PNI, respectively. On recursive partitioning analysis, PNI predicted for worse FFM and CSS in patients with GS 8-10, with FFM of 67% vs. 89% (p <0.02), and CSS of 69% vs. 91%, (p <0.04) at 7 years for those with and without PNI, respectively. Conclusions: The presence of PNI in the prostate biopsy predicts worse clinical outcome for patients treated with dose-escalated external-beam radiation therapy. Particularly in patients with GS 8-10 disease, the presence of PNI suggests an increased risk of metastasis and prostate cancer death.

  14. Age-related differences in sequential modulations of poorer-strategy effects.

    PubMed

    Lemaire, Patrick; Hinault, Thomas

    2014-01-01

    To determine how younger and older adults modulate execution of strategies across successive trials, we asked participants to accomplish a computational estimation task (i.e., provide approximate products to two-digit multiplication problems like 38 × 74). For each problem, they were cued to execute a better versus a poorer strategy. Their performance revealed sequential modulations of poorer-strategy effects (i.e., longer solution times and larger error rates when asked to execute a poorer than a better strategy). That is, poorer-strategy effects were smaller on current problems after using a poorer strategy on preceding problems than after using a better strategy. Moreover, sequential modulations of these poorer-strategy effects were smaller in older than in younger adults, especially older adults with low-cognitive control skills (as measured by conflict adaptation effects in the Simon task). Our findings suggest that these sequential modulations may result from executive control mechanisms, the efficiency of which is known to decrease in older adults. These findings have important implications regarding mechanisms underlying strategy execution and aging effects on strategic variations.

  15. Strengths and limitations of using repeat-dose toxicity studies to predict effects on fertility.

    PubMed

    Dent, M P

    2007-08-01

    The upcoming European chemicals legislation REACH (Registration, Evaluation, and Authorisation of Chemicals) will require the risk assessment of many thousands of chemicals. It is therefore necessary to develop intelligent testing strategies to ensure that chemicals of concern are identified whilst minimising the testing of chemicals using animals. Xenobiotics may perturb the reproductive cycle, and for this reason several reproductive studies are recommended under REACH. One of the endpoints assessed in this battery of tests is mating performance and fertility. Animal tests that address this endpoint use a relatively large number of animals and are also costly in terms of resource, time, and money. If it can be shown that data from non-reproductive studies such as in-vitro or repeat-dose toxicity tests are capable of generating reliable alerts for effects on fertility then some animal testing may be avoided. Available rat sub-chronic and fertility data for 44 chemicals that have been classified by the European Union as toxic to fertility were therefore analysed for concordance of effects. Because it was considered appropriate to read across data for some chemicals these data sets were considered relevant for 73 of the 102 chemicals currently classified as toxic to reproduction (fertility) under this system. For all but 5 of these chemicals it was considered that a well-performed sub-chronic toxicity study would have detected pathology in the male, and in some cases, the female reproductive tract. Three showed evidence of direct interaction with oestrogen or androgen receptors (linuron, nonylphenol, and fenarimol). The remaining chemicals (quinomethionate and azafenidin) act by modes of action that do not require direct interaction with steroid receptors. However, both these materials caused in-utero deaths in pre-natal developmental toxicity studies, and the relatively low NOAELs and the nature of the hazard identified in the sub-chronic tests provides an alert

  16. Greater emotional arousal predicts poorer long-term memory of communication skills in couples.

    PubMed

    Baucom, Brian R; Weusthoff, Sarah; Atkins, David C; Hahlweg, Kurt

    2012-06-01

    Many studies have examined the importance of learning skills in behaviorally based couple interventions but none have examined predictors of long-term memory for skills. Associations between emotional arousal and long-term recall of communication skills delivered to couples during a behaviorally based relationship distress prevention program were examined in a sample of 49 German couples. Fundamental frequency (f(0)), a vocal measure of encoded emotional arousal, was measured during pre-treatment couple conflict. Higher levels of f(0) were linked to fewer skills remembered 11 years after completing the program, and women remembered more skills than men. Implications of results for behaviorally based couple interventions are discussed.

  17. Isothermal calorimetry: a predictive tool to model drug-propellant interactions in pressurized metered dose systems.

    PubMed

    Ooi, Jesslynn; Gaisford, Simon; Boyd, Ben J; Young, Paul M; Traini, Daniela

    2014-01-30

    The purpose of this work was to evaluate gas perfusion isothermal calorimetry (ITC) as a method to characterize the physicochemical changes of active pharmaceutical ingredients (APIs) intended to be formulated in pressurized metered dose inhalers (pMDIs) after exposure to a model propellant. Spray dried samples of beclomethasone dipropionate (BDP) and salbutamol sulphate (SS) were exposed to controlled quantities of 2H,3H-decafluoropentane (HPFP) to determine whether ITC could be used as a suitable analytical method for gathering data on the behavioural properties of the powders in real time. The crystallization kinetics of BDP and the physiochemical properties of SS were successfully characterized using ITC and supported by a variety of other analytical techniques. Correlations between real and model propellant systems were also established using hydrofluoroalkane (HFA-227) propellant. In summary, ITC was found to be suitable for gathering data on the crystallization kinetics of BDP and SS. In a wider context, this work will have implications on the use of ITC for stability testing of APIs in HFA-based pMDIs.

  18. Cannabidiol is a partial agonist at dopamine D2High receptors, predicting its antipsychotic clinical dose

    PubMed Central

    Seeman, P

    2016-01-01

    Although all current antipsychotics act by interfering with the action of dopamine at dopamine D2 receptors, two recent reports showed that 800 to 1000 mg of cannabidiol per day alleviated the signs and symptoms of schizophrenia, although cannabidiol is not known to act on dopamine receptors. Because these recent clinical findings may indicate an important exception to the general rule that all antipsychotics interfere with dopamine at dopamine D2 receptors, the present study examined whether cannabidiol acted directly on D2 receptors, using tritiated domperidone to label rat brain striatal D2 receptors. It was found that cannabidiol inhibited the binding of radio-domperidone with dissociation constants of 11 nm at dopamine D2High receptors and 2800 nm at dopamine D2Low receptors, in the same biphasic manner as a dopamine partial agonist antipsychotic drug such as aripiprazole. The clinical doses of cannabidiol are sufficient to occupy the functional D2High sites. it is concluded that the dopamine partial agonist action of cannabidiol may account for its clinical antipsychotic effects. PMID:27754480

  19. Concordance between actual and pharmacogenetic predicted desvenlafaxine dose needed to achieve remission in major depressive disorder: a 10-week open-label study

    PubMed Central

    Müller, Daniel J.; Ng, Chee H.; Byron, Keith; Berk, Michael; Singh, Ajeet B.

    2017-01-01

    Background Pharmacogenetic-based dosing support tools have been developed to personalize antidepressant-prescribing practice. However, the clinical validity of these tools has not been adequately tested, particularly for specific antidepressants. Objective To examine the concordance between the actual dose and a polygene pharmacogenetic predicted dose of desvenlafaxine needed to achieve symptom remission. Materials and methods A 10-week, open-label, prospective trial of desvenlafaxine among Caucasian adults with major depressive disorder (n=119) was conducted. Dose was clinically adjusted and at the completion of the trial, the clinical dose needed to achieve remission was compared with the predicted dose needed to achieve remission. Results Among remitters (n=95), there was a strong concordance (Kendall’s τ-b=0.84, P=0.0001; Cohen’s κ=0.82, P=0.0001) between the actual and the predicted dose need to achieve symptom remission, showing high sensitivity (≥85%), specificity (≥86%), and accuracy (≥89%) of the tool. Conclusion Findings provide initial evidence for the clinical validity of a polygene pharmacogenetic-based tool for desvenlafaxine dosing. PMID:27779571

  20. Assessment of uncertainties in radiation-induced cancer risk predictions at clinically relevant doses

    SciTech Connect

    Nguyen, J.; Moteabbed, M.; Paganetti, H.

    2015-01-15

    Purpose: Theoretical dose–response models offer the possibility to assess second cancer induction risks after external beam therapy. The parameters used in these models are determined with limited data from epidemiological studies. Risk estimations are thus associated with considerable uncertainties. This study aims at illustrating uncertainties when predicting the risk for organ-specific second cancers in the primary radiation field illustrated by choosing selected treatment plans for brain cancer patients. Methods: A widely used risk model was considered in this study. The uncertainties of the model parameters were estimated with reported data of second cancer incidences for various organs. Standard error propagation was then subsequently applied to assess the uncertainty in the risk model. Next, second cancer risks of five pediatric patients treated for cancer in the head and neck regions were calculated. For each case, treatment plans for proton and photon therapy were designed to estimate the uncertainties (a) in the lifetime attributable risk (LAR) for a given treatment modality and (b) when comparing risks of two different treatment modalities. Results: Uncertainties in excess of 100% of the risk were found for almost all organs considered. When applied to treatment plans, the calculated LAR values have uncertainties of the same magnitude. A comparison between cancer risks of different treatment modalities, however, does allow statistically significant conclusions. In the studied cases, the patient averaged LAR ratio of proton and photon treatments was 0.35, 0.56, and 0.59 for brain carcinoma, brain sarcoma, and bone sarcoma, respectively. Their corresponding uncertainties were estimated to be potentially below 5%, depending on uncertainties in dosimetry. Conclusions: The uncertainty in the dose–response curve in cancer risk models makes it currently impractical to predict the risk for an individual external beam treatment. On the other hand, the ratio

  1. Dosimetric verification of IMAT delivery with a conventional EPID system and a commercial portal dose image prediction tool

    SciTech Connect

    Iori, Mauro; Cagni, Elisabetta; Paiusco, Marta; Munro, Peter; Nahum, Alan E.

    2010-01-15

    Purpose: The electronic portal imaging device (EPID) is a system for checking the patient setup; as a result of its integration with the linear accelerator and software customized for dosimetry, it is increasingly used for verification of the delivery of fixed-field intensity-modulated radiation therapy (IMRT). In order to extend such an approach to intensity-modulated arc therapy (IMAT), the combined use of an EPID system and a portal dose image prediction (PDIP) tool has been investigated. Methods: The dosimetric behavior of an EPID system, mechanically reinforced to maintain its positional stability during the accelerator gantry rotation, has been studied to assess its ability to measure portal dose distributions for IMAT treatment beams. In addition, the PDIP tool of a commercial treatment planning system, commonly used for static IMRT dosimetry, has been validated for simulating the PDIs of IMAT treatment fields. The method has been applied to the delivery verification of 23 treatment fields that were measured in their dual mode of IMRT and IMAT modalities. Results: The EPID system has proved to be appropriate for measuring the PDIs of IMAT fields; additionally the PDIP tool was able to simulate these accurately. The results are quite similar to those obtained for static IMRT treatment verification, although it was necessary to investigate the dependence of the EPID signal and of the accelerator monitor chamber response on variable dose rate. Conclusions: Our initial tests indicate that the EPID system, together with the PDIP tool, is a suitable device for the verification of IMAT plan delivery; however, additional tests are necessary to confirm these results.

  2. Standard-Fractionated Radiotherapy for Optic Nerve Sheath Meningioma: Visual Outcome Is Predicted by Mean Eye Dose

    SciTech Connect

    Abouaf, Lucie; Girard, Nicolas; Lefort, Thibaud; D'hombres, Anne; Tilikete, Caroline; Vighetto, Alain; Mornex, Francoise

    2012-03-01

    Purpose: Radiotherapy has shown its efficacy in controlling optic nerve sheath meningiomas (ONSM) tumor growth while allowing visual acuity to improve or stabilize. However, radiation-induced toxicity may ultimately jeopardize the functional benefit. The purpose of this study was to identify predictive factors of poor visual outcome in patients receiving radiotherapy for ONSM. Methods and Materials: We conducted an extensive analysis of 10 patients with ONSM with regard to clinical, radiologic, and dosimetric aspects. All patients were treated with conformal radiotherapy and subsequently underwent biannual neuroophthalmologic and imaging assessments. Pretreatment and posttreatment values of visual acuity and visual field were compared with Wilcoxon's signed rank test. Results: Visual acuity values significantly improved after radiotherapy. After a median follow-up time of 51 months, 6 patients had improved visual acuity, 4 patients had improved visual field, 1 patient was in stable condition, and 1 patient had deteriorated visual acuity and visual field. Tumor control rate was 100% at magnetic resonance imaging assessment. Visual acuity deterioration after radiotherapy was related to radiation-induced retinopathy in 2 patients and radiation-induced mature cataract in 1 patient. Study of radiotherapy parameters showed that the mean eye dose was significantly higher in those 3 patients who had deteriorated vision. Conclusions: Our study confirms that radiotherapy is efficient in treating ONSM. Long-term visual outcome may be compromised by radiation-induced side effects. Mean eye dose has to be considered as a limiting constraint in treatment planning.

  3. Subjective relative deprivation is associated with poorer physical and mental health.

    PubMed

    Mishra, Sandeep; Carleton, R Nicholas

    2015-12-01

    Substantial epidemiological evidence has shown that income inequality and objective measures of relative deprivation are associated with poorer health outcomes. However, surprisingly little research has examined whether subjective feelings of relative deprivation are similarly linked with poorer health outcomes. The relative deprivation hypothesis suggests that inequality affects health at the individual level through negative consequences of social comparison. We directly examined the relationship between subjective feelings of personal relative deprivation and self-reported physical and mental health in a diverse community sample (n = 328). Results demonstrated that subjective feelings of personal relative deprivation are associated with significantly poorer physical and mental health. These relationships held even when accounting for covariates that have been previously associated with both relative deprivation and health. These results further support the link between relative deprivation and health outcomes and suggest that addressing root causes of relative deprivation may lead to greater individual health.

  4. Predictive factors for erectile dysfunction in men with prostate cancer after brachytherapy: Is dose to the penile bulb important?

    SciTech Connect

    Macdonald, A. Graham . E-mail: gmacdonald@easynet.co.uk; Keyes, Mira; Kruk, Alexandra; Duncan, Graeme; Moravan, Veronika; Morris, W. James

    2005-09-01

    Purpose: To determine predictive factors for postimplant erectile dysfunction (ED) in a cohort of patients, according to prospectively collected data; specifically, to assess the impact of penile bulb volume and D50 and D95 (dose covering 50% and 95% of the penile bulb volume, respectively) on ED. Methods and Materials: Three hundred forty-two patients were identified who were potent before implant and who had at least 2 years' follow-up. Patient, tumor, treatment, and dosimetric data were collected on all patients. Postimplant ED was defined according to both physician-documented and patient-documented outcome data. Binary logistic regression analysis was used to create multivariable models of predictors for ED at 1, 2, and 3 years after implant. Results: Physician-documented rates of ED were 57%, 48%, and 38% at 1, 2, and 3 years after implant, respectively. Patient-documented rates of ED were 70% and 66% at 1 and 2 years, respectively. Multivariable analyses revealed age and degree of preimplant erectile function to be consistently significant predictors of ED. Use of hormones was significant at the 1-year physician-documented ED endpoint but not thereafter, in keeping with the time course of testosterone recovery. Penile bulb volume, D50, and D95 were not found to be predictive for ED at any time point, in contrast to previous studies. In addition, planning ultrasound target volume, number of needles, and institutional case sequence number were significant predictors of ED at various time points, consistent with a traumatic etiology of ED. Conclusions: We found no evidence to support penile bulb dosimetry as an independent predictive factor for ED after implant, using physician-documented or patient-documented outcomes.

  5. Little Evidence for Usefulness of Biomarkers for Predicting Successful Dose Reduction or Discontinuation of a Biologic Agent in Rheumatoid Arthritis: A Systematic Review

    PubMed Central

    van den Ende, Cornelia H.; Beeren, Fenna M. M.; Been, Evelien M. J.; van den Hoogen, Frank H. J.; den Broeder, Alfons A.

    2017-01-01

    Objective To systematically review studies addressing prediction of successful dose reduction or discontinuation of a biologic agent in rheumatoid arthritis (RA). Methods PubMed, Embase, and Cochrane Library databases were searched for studies that examined the predictive value of biomarkers for successful dose reduction or discontinuation of a biologic agent in RA. Two reviewers independently selected studies, and extracted data and assessed the risk of bias. A biomarker was classified as a “potential predictor” if the univariate association was either strong (odds ratio or hazard ratio >2.0 or <0.5) or statistically significant. For biomarkers that were studied multiple times, qualitative best‐evidence synthesis was performed separately for the prediction of successful dose reduction and discontinuation. Biomarkers that were defined in ≥75% of the studies as potential predictors were regarded as “predictor” for the purposes of our study. Results Of 3,029 nonduplicate articles initially searched, 16 articles regarding 15 cohorts were included in the present study. Overall, 17 biomarkers were studied multiple times for the prediction of successful dose reduction, and 33 for the prediction of successful discontinuation of a biologic agent. Three predictors were identified: higher adalimumab trough level for successful dose reduction and lower Sharp/van der Heijde erosion score and shorter symptom duration at the start of a biologic agent for successful discontinuation. Conclusion The predictive value of a wide variety of biomarkers for successful dose reduction or discontinuation of biologic treatment in RA has been investigated. We identified only 3 biomarkers as predictors, in just 2 studies. The strength of the evidence is limited by the low quality of the included studies and the likelihood of reporting bias and multiple testing. PMID:27696778

  6. Modeling of Salivary Production Recovery After Radiotherapy Using Mixed Models: Determination of Optimal Dose Constraint for IMRT Planning and Construction of Convenient Tools to Predict Salivary Function

    SciTech Connect

    Ortholan, Cecile Chamorey, Emmanuel Phar; Benezery, Karen; Thariat, Juliette; Dassonville, Olivier; Poissonnet, Gilles; Bozec, Alexandre; Follana, Philippe; Peyrade, Frederique; Sudaka, Anne; Gerard, Jean Pierre; Bensadoun, Rene Jean

    2009-01-01

    Purpose: The mathematical relationship between the dose to the parotid glands and salivary gland production needs to be elucidated. This study, which included data from patients included in a French prospective study assessing the benefit of intensity-modulated radiotherapy (RT), sought to elaborate a convenient and original model of salivary recovery. Methods and Materials: Between January 2001 and December 2004, 44 patients were included (35 with oropharyngeal and 9 with nasopharyngeal cancer). Of the 44 patients, 24 were treated with intensity-modulated RT, 17 with three-dimensional conformal RT, and 2 with two-dimensional RT. Stimulated salivary production was collected for {<=}24 months after RT. The data of salivary production, time of follow-up, and dose to parotid gland were modeled using a mixed model. Several models were developed to assess the best-fitting variable for the dose level to the parotid gland. Results: Models developed with the dose to the contralateral parotid fit the data slightly better than those with the dose to both parotids, suggesting that contralateral and ipsilateral parotid glands are not functionally equivalent even with the same dose level to the glands. The best predictive dose-value variable for salivary flow recovery was the volume of the contralateral parotid gland receiving >40 Gy. Conclusion: The results of this study show that the recommendation of a dose constraint for intensity-modulated RT planning should be established at the volume of the contralateral parotid gland receiving >40 Gy rather than the mean dose. For complete salivary production recovery after 24 months, the volume of the contralateral parotid gland receiving >40 Gy should be <33%. Our results permitted us to establish two convenient tools to predict the saliva production recovery function according to the dose received by the contralateral parotid gland.

  7. Children's Executive Functions: Are They Poorer after Very Early Brain Insult

    ERIC Educational Resources Information Center

    Anderson, Vicki; Spencer-Smith, Megan; Coleman, Lee; Anderson, Peter; Williams, Jackie; Greenham, Mardee; Leventer, Richard J.; Jacobs, Rani

    2010-01-01

    Traditionally early brain insult (EBI) has been considered to have better outcome than later injury, consistent with the notion that the young brain is flexible and able to reorganize. Recent research findings question this view, suggesting that EBI might lead to poorer outcome than brain insult at any other age. Exploring this early vulnerability…

  8. Automated pediatric abdominal effective diameter measurements versus age-predicted body size for normalization of CT dose.

    PubMed

    Cheng, Phillip M; Vachon, Linda A; Duddalwar, Vinay A

    2013-12-01

    There has been increasing interest in adjusting CT radiation dose data for patient body size. A method for automated computation of the abdominal effective diameter of a patient from a CT image has previously only been tested in adult patients. In this work, we tested the method on a set of 128 pediatric patients aged 0.8 to 12.9 years (average 8.0 years, SD = 3.7 years) who had CT abdomen/pelvis exams performed on a Toshiba Aquilion 64 scanner. For this set of patients, age-predicted abdominal effective diameter extrapolated based on data from the International Commission on Radiation Units and Measurements was a relatively poor predictor of measured effective diameter. The mean absolute percentage error between the CTDI normalization coefficient calculated from a manually measured effective diameter and the coefficient determined by age-predicted effective diameter was 12.3 % with respect to a 32 cm phantom (range 0.0-52.8 %, SD 8.7 %) and 12.9 % with respect to a 16 cm phantom (range 0.0-56.4 %, SD 9.2 %). In contrast, there is a close correspondence between the automated and manually measured patient effective diameters, with a mean absolute error of 0.6 cm (error range 0.2-1.3 cm). This correspondence translates into a high degree of correspondence between normalization coefficients determined by automated and manual measurements; the mean absolute percentage error was 2.1 % with respect to a 32 cm phantom (range 0.0-8.1 %, SD = 1.4 %) and 2.3 % with respect to a 16 cm phantom (range 0.0-9.3 %, SD = 1.6 %).

  9. Variable selection models based on multiple imputation with an application for predicting median effective dose and maximum effect

    PubMed Central

    Wan, Y.; Datta, S.; Conklin, D.J.; Kong, M.

    2015-01-01

    The statistical methods for variable selection and prediction could be challenging when missing covariates exist. Although multiple imputation (MI) is a universally accepted technique for solving missing data problem, how to combine the MI results for variable selection is not quite clear, because different imputations may result in different selections. The widely applied variable selection methods include the sparse partial least-squares (SPLS) method and the penalized least-squares method, e.g. the elastic net (ENet) method. In this paper, we propose an MI-based weighted elastic net (MI-WENet) method that is based on stacked MI data and a weighting scheme for each observation in the stacked data set. In the MI-WENet method, MI accounts for sampling and imputation uncertainty for missing values, and the weight accounts for the observed information. Extensive numerical simulations are carried out to compare the proposed MI-WENet method with the other competing alternatives, such as the SPLS and ENet. In addition, we applied the MIWENet method to examine the predictor variables for the endothelial function that can be characterized by median effective dose (ED50) and maximum effect (Emax) in an ex-vivo phenylephrine-induced extension and acetylcholine-induced relaxation experiment. PMID:26412909

  10. Predictive Dose-Based Estimation of Systemic Exposure Multiples in Mouse and Monkey Relative to Human for Antisense Oligonucleotides With 2′-O-(2-Methoxyethyl) Modifications

    PubMed Central

    Yu, Rosie Z; Grundy, John S; Henry, Scott P; Kim, Tae-Won; Norris, Daniel A; Burkey, Jennifer; Wang, Yanfeng; Vick, Andrew; Geary, Richard S

    2015-01-01

    Evaluation of species differences and systemic exposure multiples (or ratios) in toxicological animal species versus human is an ongoing exercise during the course of drug development. The systemic exposure ratios are best estimated by directly comparing area under the plasma concentration-time curves (AUCs), and sometimes by comparing the dose administered, with the dose being adjusted either by body surface area (BSA) or body weight (BW). In this study, the association between AUC ratio and the administered dose ratio from animals to human were studied using a retrospective data-driven approach. The dataset included nine antisense oligonucleotides (ASOs) with 2′-O-(2-methoxyethyl) modifications, evaluated in two animal species (mouse and monkey) following single and repeated parenteral administrations. We found that plasma AUCs were similar between ASOs within the same species, and are predictable to human exposure using a single animal species, either mouse or monkey. Between monkey and human, the plasma exposure ratio can be predicted directly based on BW-adjusted dose ratios, whereas between mouse and human, the exposure ratio would be nearly fivefold lower in mouse compared to human based on BW-adjusted dose values. Thus, multiplying a factor of 5 for the mouse BW-adjusted dose would likely provide a reasonable AUC exposure estimate in human at steady-state. PMID:25602582

  11. Estimation of plasma area under the curve for etanidazole (SR 2508) in toxicity prediction and dose adjustment

    SciTech Connect

    Workman, P.; Ward, R.; Maughan, T.S.; Newman, H.F.; Bleehen, N.M.

    1989-07-01

    The hydrophilic 2-nitroimidazole radiosensitizer etanidazole is currently undergoing clinical evaluation. Although considerably less neurotoxic than misonidazole because of its rapid renal clearance and partial exclusion from the nervous system, total dose is limited by peripheral neuropathy. Monitoring plasma etanidazole concentration in patients to determine the area under the curve (AUC0-infinity) has been proposed as a method of predicting patients at risk, and of providing a quantitative basis for dose reduction in such patients. Successful application of this policy requires accurate assessment of AUC0-infinity. We have analyzed plasma data for 18 patients receiving 2 g/m2 etanidazole to determine the errors introduced in the estimation of AUC0-infinity caused by omitting selected time points from the analysis. A 'baseline' AUC0-infinity value was calculated by integration of the rate equation for the 2-compartment model using data points at 0, 15, and 30 min and 1, 2, 4, 8, 12, and 24 hr after the end of infusion. The mean +/- SD area for AUC0-infinity was 502 +/- 152 micrograms ml-1 h (2.35 +/- 0.71 mM.h). Omitting the zero or the 24 hr time point, the average errors were quite small (2.5% in both cases), but errors of up to 16.4 and 7.3%, respectively, were seen for individual patients. Leaving out both the 8 hr and 12 hr points at the same time gave a similar low average error of 2.9%, with a highest error of 7.3%. Omitting all data points after 4 hr, the mean error was 24.7% and 15 of 18 patients had errors in excess of 10%. In addition, failure to correct for infusion time results in an underestimation of AUC0-infinity averaging 4.5% (range 1.9-8.7%). The choice of sampling times for toxicological monitoring will depend upon the accuracy with which the AUC0-infinity must be known. Including all data points between 0 and 24 hr will minimize errors.

  12. Diabetes Mellitus and Poorer Prognosis in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

    PubMed Central

    Wang, Yan-Gang; Wang, Peng; Wang, Bin; Fu, Zheng-Ju; Zhao, Wen-Juan; Yan, Sheng-Li

    2014-01-01

    Background Previous studies suggested that diabetes mellitus was associated with cancer risk and prognosis, but studies investigating the relationship between diabetes mellitus and survival in patients with hepatocellular carcinoma (HCC) reported inconsistent findings. To derive a more precise estimate of the prognostic role of diabetes mellitus in HCC, we systematically reviewed published studies and carried out a meta-analysis. Methods Eligible articles were identified in electronic databases from their inception through September 16, 2013. To evaluate the correlation between diabetes mellitus and prognosis in HCC, the pooled hazard ratios (HR) and their 95% confidence intervals (95% CI) for poorer overall and disease-free survivals were calculated by standard meta-analysis techniques with fixed-effects or random-effects models. Results 21 studies with a total of 9,767 HCC patients stratifying overall survival and/or disease-free survival in HCC patients by diabetes mellitus status were eligible for meta-analysis. 20 studies with a total of 9,727 HCC cases investigated the overall survival, and 10 studies with a total of 2,412 HCC patients investigated the disease-free survival. The pooled HRs for overall survival and disease-free survival were 1.46 (95% CI, 1.29 to 1.66; P<0.001) and 1.57 (95% CI, 1.21 to 2.05; P = 0.001), respectively. The adjusted HRs for overall survival and disease-free survival were 1.55 (95% CI, 1.27 to 1.91; P<0.001) and 2.15 (95% CI, 1.75 to 2.63; P<0.001), respectively. In addition, for patients receiving hepatic resection, diabetes mellitus was associated with both poorer overall survival and poorer disease-free survival, and for patients receiving non-surgical treatment or patients receiving radiofrequency ablation, diabetes mellitus was associated with poorer overall survival. There was no evidence for publication bias. Conclusion Diabetes mellitus is independently associated with both poorer overall survival and poorer disease

  13. Altered tract-specific white matter microstructure is related to poorer cognitive performance: The Rotterdam Study.

    PubMed

    Cremers, Lotte G M; de Groot, Marius; Hofman, Albert; Krestin, Gabriel P; van der Lugt, Aad; Niessen, Wiro J; Vernooij, Meike W; Ikram, M Arfan

    2016-03-01

    White matter microstructural integrity has been related to cognition. Yet, the potential role of specific white matter tracts on top of a global white matter effect remains unclear, especially when considering specific cognitive domains. Therefore, we determined the tract-specific effect of white matter microstructure on global cognition and specific cognitive domains. In 4400 nondemented and stroke-free participants (mean age 63.7 years, 55.5% women), we obtained diffusion magnetic resonance imaging parameters (fractional anisotropy and mean diffusivity) in 14 white matter tracts using probabilistic tractography and assessed cognitive performance with a cognitive test battery. Tract-specific white matter microstructure in all supratentorial tracts was associated with poorer global cognition. Lower fractional anisotropy in association tracts, primarily the inferior fronto-occipital fasciculus, and higher mean diffusivity in projection tracts, in particular the posterior thalamic radiation, most strongly related to poorer cognition. Altered white matter microstructure related to poorer information processing speed, executive functioning, and motor speed, but not to memory. Tract-specific microstructural changes may aid in better understanding the mechanism of cognitive impairment and neurodegenerative diseases.

  14. LETTER TO THE EDITOR: Comments on 'Reconsidering the definition of a dose volume histogram'—dose mass histogram (DMH) versus dose volume histogram (DVH) for predicting radiation-induced pneumonitis

    NASA Astrophysics Data System (ADS)

    Mavroidis, Panayiotis; Plataniotis, Georgios A.; Adamus Górka, Magdalena; Lind, Bengt K.

    2006-12-01

    In a recently published paper (Nioutsikou et al 2005 Phys. Med. Biol. 50 L17) the authors showed that the use of the dose-mass histogram (DMH) concept is a more accurate descriptor of the dose delivered to lung than the traditionally used dose-volume histogram (DVH) concept. Furthermore, they state that if a functional imaging modality could also be registered to the anatomical imaging modality providing a functional weighting across the organ (functional mass) then the more general and realistic concept of the dose-functioning mass histogram (D[F]MH) could be an even more appropriate descriptor. The comments of the present letter to the editor are in line with the basic arguments of that work since their general conclusions appear to be supported by the comparison of the DMH and DVH concepts using radiobiological measures. In this study, it is examined whether the dose-mass histogram (DMH) concept deviated significantly from the widely used dose-volume histogram (DVH) concept regarding the expected lung complications and if there are clinical indications supporting these results. The problem was investigated theoretically by applying two hypothetical dose distributions (Gaussian and semi-Gaussian shaped) on two lungs of uniform and varying densities. The influence of the deviation between DVHs and DMHs on the treatment outcome was estimated by using the relative seriality and LKB models using the Gagliardi et al (2000 Int. J. Radiat. Oncol. Biol. Phys. 46 373) and Seppenwoolde et al (2003 Int. J. Radiat. Oncol. Biol. Phys. 55 724) parameter sets for radiation pneumonitis, respectively. Furthermore, the biological equivalent of their difference was estimated by the biologically effective uniform dose (\\bar{\\bar{D}}) and equivalent uniform dose (EUD) concepts, respectively. It is shown that the relation between the DVHs and DMHs varies depending on the underlying cell density distribution and the applied dose distribution. However, the range of their deviation in

  15. SU-D-201-02: Prediction of Delivered Dose Based On a Joint Histogram of CT and FDG PET Images

    SciTech Connect

    Park, M; Choi, Y; Cho, A; Hwang, S; Cha, J; Lee, N; Yun, M

    2015-06-15

    Purpose: To investigate whether pre-treatment images can be used in predicting microsphere distribution in tumors. When intra-arterial radioembolization using Y90 microspheres was performed, the microspheres were often delivered non-uniformly within the tumor, which could lead to an inefficient therapy. Therefore, it is important to estimate the distribution of microspheres. Methods: Early arterial phase CT and FDG PET images were acquired for patients with primary liver cancer prior to radioembolization (RE) using Y90 microspheres. Tumor volume was delineated on CT images and fused with FDG PET images. From each voxel (3.9×3.9×3.3 mm3) in the tumor, the Hounsfield unit (HU) from the CT and SUV values from the FDG PET were harvested. We binned both HU and SUV into 11 bins and then calculated a normalized joint-histogram in an 11×11 array.Patients also underwent a post-treatment Y90 PET imaging. Radiation dose for the tumor was estimated using convolution of the Y90 distribution with a dose-point kernel. We also calculated a fraction of the tumor volume that received a radiation dose great than 100Gy. Results: Averaged over 40 patients, 55% of tumor volume received a dose greater than 100Gy (range : 1.1 – 100%). The width of the joint histogram was narrower for patients with a high dose. For patients with a low dose, the width was wider and a larger fraction of tumor volume had low HU. Conclusion: We have shown the pattern of joint histogram of the HU and SUV depends on delivered dose. The patterns can predict the efficacy of uniform intra-arterial delivery of Y90 microspheres.

  16. Dose Addition Models Based on Biologically Relevant Reductions in Fetal Testosterone Accurately Predict Postnatal Reproductive Tract Alterations by a Phthalate Mixture in Rats

    PubMed Central

    Howdeshell, Kembra L.; Rider, Cynthia V.; Wilson, Vickie S.; Furr, Johnathan R.; Lambright, Christy R.; Gray, L. Earl

    2015-01-01

    Challenges in cumulative risk assessment of anti-androgenic phthalate mixtures include a lack of data on all the individual phthalates and difficulty determining the biological relevance of reduction in fetal testosterone (T) on postnatal development. The objectives of the current study were 2-fold: (1) to test whether a mixture model of dose addition based on the fetal T production data of individual phthalates would predict the effects of a 5 phthalate mixture on androgen-sensitive postnatal male reproductive tract development, and (2) to determine the biological relevance of the reductions in fetal T to induce abnormal postnatal reproductive tract development using data from the mixture study. We administered a dose range of the mixture (60, 40, 20, 10, and 5% of the top dose used in the previous fetal T production study consisting of 300 mg/kg per chemical of benzyl butyl (BBP), di(n)butyl (DBP), diethyl hexyl phthalate (DEHP), di-isobutyl phthalate (DiBP), and 100 mg dipentyl (DPP) phthalate/kg; the individual phthalates were present in equipotent doses based on their ability to reduce fetal T production) via gavage to Sprague Dawley rat dams on GD8-postnatal day 3. We compared observed mixture responses to predictions of dose addition based on the previously published potencies of the individual phthalates to reduce fetal T production relative to a reference chemical and published postnatal data for the reference chemical (called DAref). In addition, we predicted DA (called DAall) and response addition (RA) based on logistic regression analysis of all 5 individual phthalates when complete data were available. DA ref and DA all accurately predicted the observed mixture effect for 11 of 14 endpoints. Furthermore, reproductive tract malformations were seen in 17–100% of F1 males when fetal T production was reduced by about 25–72%, respectively. PMID:26350170

  17. The impact of uncertainties in the CT conversion algorithm when predicting proton beam ranges in patients from dose and PET-activity distributions.

    PubMed

    España, Samuel; Paganetti, Harald

    2010-12-21

    The advantages of a finite range of proton beams can only be partly exploited in radiation therapy unless the range can be predicted in patient anatomy with <2 mm accuracy (for non-moving targets). Monte Carlo dose calculation aims at 1-2 mm accuracy in dose prediction, and proton-induced PET imaging aims at ∼2 mm accuracy in range verification. The latter is done using Monte Carlo predicted PET images. Monte Carlo methods are based on CT images to describe patient anatomy. The dose calculation algorithm and the CT resolution/artifacts might affect dose calculation accuracy. Additionally, when using Monte Carlo for PET range verification, the biological decay model and the cross sections for positron emitter production affect predicted PET images. The goal of this work is to study the effect of uncertainties in the CT conversion on the proton beam range predicted by Monte Carlo dose calculations and proton-induced PET signals. Conversion schemes to assign density and elemental composition based on a CT image of the patient define a unique Hounsfield unit (HU) to tissue parameters relationship. Uncertainties are introduced because there is no unique relationship between HU and tissue parameters. In this work, different conversion schemes based on a stoichiometric calibration method as well as different numbers of tissue bins were considered in three head and neck patients. For Monte Carlo dose calculation, the results show close to zero (<0.5 mm) differences in range using different conversion schemes. Further, a reduction of the number of bins used to define individual tissues down to 13 did not affect the accuracy. In the case of simulated PET images we found a more pronounced sensitivity on the CT conversion scheme with a mean fall-off position variation of about 1 mm. We conclude that proton dose distributions based on Monte Carlo calculation are only slightly affected by the uncertainty on density and elemental composition introduced by unique assignment to

  18. Radiation dose to the tongue and velopharynx predicts acoustic-articulatory changes after chemo-IMRT treatment for advanced head and neck cancer.

    PubMed

    Jacobi, Irene; Navran, Arash; van der Molen, Lisette; Heemsbergen, Wilma D; Hilgers, Frans J M; van den Brekel, Michiel W M

    2016-02-01

    The aim of this study was to investigate to what extent changes in speech after C-IMRT treatment are related to mean doses to the tongue and velopharynx (VP). In 34 patients with advanced hypopharyngeal, nasopharyngeal, or oropharyngeal cancer, changes in speech from pretreatment to 10 weeks and 1 year posttreatment were correlated with mean doses to the base of tongue (BOT), oral cavity (OC) and tonsillar fossa/soft palate (VP). Differences in anteroposterior tongue position, dorsoventral degree of tongue to palate or pharynx constriction, grooving, strength, nasality, and laryngeal rise, were assessed by acoustic changes in three speech sounds that depend on a (post-) alveolar closure or narrowing (/t/, /s/, /z/), three with a tongue to palate/pharyngeal narrowing (/l/, /r/, /u/), and in vowel /a/ at comfortable and highest pitch. Acoustically assessed changes in tongue positioning, shape, velopharyngeal constriction, and laryngeal elevation were significantly related to mean doses to the tongue and velopharynx. The mean dose to BOT predicted changes in anteroposterior tongue positioning from pre- to 10-weeks posttreatment. From pretreatment to 1-year, mean doses to BOT, OC, and VP were related to changes in grooving, strength, laryngeal height, nasality, palatalization, and degree of pharyngeal constriction. Changes in speech are related to mean doses to the base of tongue and velopharynx. The outcome indicates that strength, motility, and the balance between agonist and antagonist muscle forces change significantly after radiotherapy.

  19. From active shape model to active optical flow model: a shape-based approach to predicting voxel-level dose distributions in spine SBRT.

    PubMed

    Liu, Jianfei; Wu, Q Jackie; Kirkpatrick, John P; Yin, Fang-Fang; Yuan, Lulin; Ge, Yaorong

    2015-03-07

    Prediction of achievable dose distribution in spine stereotactic body radiation therapy (SBRT) can help in designing high-quality treatment plans to maximally protect spinal cords and to effectively control tumours. Dose distributions at spinal cords are primarily affected by the shapes of adjacent planning target volume (PTV) contours. In this work, we estimate such contour effects and predict dose distributions by exploring active optical flow model (AOFM) and active shape model (ASM). We first collect a sequence of dose sub-images and PTV contours near spinal cords from fifteen SBRT plans in the training dataset. The data collection is then classified into five groups according to the PTV locations in relation to spinal cords. In each group, we randomly choose a dose sub-image as the reference and register all other sub-images to the reference using an optical flow method. AOFM is then constructed by importing optical flow vectors and dose values into the principal component analysis (PCA). Similarly, we build ASM by using PCA on PTV contour points. The correlation between ASM and AOFM is estimated via a stepwise multiple regression model. When predicting dose distribution of a new case, the group is first determined based on the PTV contour. The prediction model of the selected group is used to estimate dose distributions by mapping the PTV contours from the ASM space to the AOFM space. This method was validated on fifteen SBRT plans in the testing dataset. Analysis of dose-volume histograms revealed that the important D2%, D5%, D10% and D0.1cc dosimetric parameters of spinal cords between the prediction and the clinical plans were 11.7 ± 1.7 Gy versus 11.8 ± 1.7 Gy (p = 0.95), 10.9 ± 1.7 Gy versus 11.1 ± 1.9 Gy (p = 0.8295), 10.2 ± 1.6 Gy versus 10.1 ± 1.7 (p = 0.9036) and 11.2 ± 2.0 Gy versus 11.1 ± 2.2 Gy (p = 0.5208), respectively. Here, the ‘cord’ is the spinal cord proper (not the thecal sac) extended 5 mm inferior and superior to the involved

  20. From active shape model to active optical flow model: a shape-based approach to predicting voxel-level dose distributions in spine SBRT

    NASA Astrophysics Data System (ADS)

    Liu, Jianfei; Wu, Q. Jackie; Kirkpatrick, John P.; Yin, Fang-Fang; Yuan, Lulin; Ge, Yaorong

    2015-03-01

    Prediction of achievable dose distribution in spine stereotactic body radiation therapy (SBRT) can help in designing high-quality treatment plans to maximally protect spinal cords and to effectively control tumours. Dose distributions at spinal cords are primarily affected by the shapes of adjacent planning target volume (PTV) contours. In this work, we estimate such contour effects and predict dose distributions by exploring active optical flow model (AOFM) and active shape model (ASM). We first collect a sequence of dose sub-images and PTV contours near spinal cords from fifteen SBRT plans in the training dataset. The data collection is then classified into five groups according to the PTV locations in relation to spinal cords. In each group, we randomly choose a dose sub-image as the reference and register all other sub-images to the reference using an optical flow method. AOFM is then constructed by importing optical flow vectors and dose values into the principal component analysis (PCA). Similarly, we build ASM by using PCA on PTV contour points. The correlation between ASM and AOFM is estimated via a stepwise multiple regression model. When predicting dose distribution of a new case, the group is first determined based on the PTV contour. The prediction model of the selected group is used to estimate dose distributions by mapping the PTV contours from the ASM space to the AOFM space. This method was validated on fifteen SBRT plans in the testing dataset. Analysis of dose-volume histograms revealed that the important D2%, D5%, D10% and D0.1cc dosimetric parameters of spinal cords between the prediction and the clinical plans were 11.7  ±  1.7 Gy versus 11.8  ±  1.7 Gy (p = 0.95), 10.9  ±  1.7 Gy versus 11.1  ±  1.9 Gy (p = 0.8295), 10.2  ±  1.6 Gy versus 10.1  ±  1.7 (p = 0.9036) and 11.2  ±  2.0 Gy versus 11.1  ±  2.2 Gy (p = 0.5208), respectively. Here, the ‘cord’ is the spinal cord proper (not the

  1. Sequential modulations of poorer-strategy effects during strategy execution: an event-related potential study in arithmetic.

    PubMed

    Hinault, Thomas; Dufau, Stéphane; Lemaire, Patrick

    2014-11-01

    When participants accomplish cognitive tasks, they obtain poorer performance if asked to execute a poorer strategy than a better strategy on a given problem. These poorer-strategy effects are smaller following execution of a poorer strategy relative to following a better strategy. To investigate ERP correlates of sequential modulations of poorer-strategy effects, we asked participants (n=20) to accomplish a computational estimation task (i.e., provide approximate products to two-digit multiplication problems like 38×74). For each problem, they were cued to execute a better versus a poorer strategy. We found event-related potentials signatures of sequential modulations of poorer-strategy effects in two crucial windows (i.e., between 200 and 550 ms and between 850 and 1250 ms) associated with executive control mechanisms and allowing conflict monitoring between the better and the cued strategy. These results have important implications on theories of strategies as they suggest that sequential modulations of poorer-strategy effects involve earlier as well as later mechanisms of cognitive control during strategy execution.

  2. Temporal Lobe Reactions After Carbon Ion Radiation Therapy: Comparison of Relative Biological Effectiveness–Weighted Tolerance Doses Predicted by Local Effect Models I and IV

    SciTech Connect

    Gillmann, Clarissa; Jäkel, Oliver; Schlampp, Ingmar; Karger, Christian P.

    2014-04-01

    Purpose: To compare the relative biological effectiveness (RBE)–weighted tolerance doses for temporal lobe reactions after carbon ion radiation therapy using 2 different versions of the local effect model (LEM I vs LEM IV) for the same patient collective under identical conditions. Methods and Materials: In a previous study, 59 patients were investigated, of whom 10 experienced temporal lobe reactions (TLR) after carbon ion radiation therapy for low-grade skull-base chordoma and chondrosarcoma at Helmholtzzentrum für Schwerionenforschung (GSI) in Darmstadt, Germany in 2002 and 2003. TLR were detected as visible contrast enhancements on T1-weighted MRI images within a median follow-up time of 2.5 years. Although the derived RBE-weighted temporal lobe doses were based on the clinically applied LEM I, we have now recalculated the RBE-weighted dose distributions using LEM IV and derived dose-response curves with Dmax,V-1 cm³ (the RBE-weighted maximum dose in the remaining temporal lobe volume, excluding the volume of 1 cm³ with the highest dose) as an independent dosimetric variable. The resulting RBE-weighted tolerance doses were compared with those of the previous study to assess the clinical impact of LEM IV relative to LEM I. Results: The dose-response curve of LEM IV is shifted toward higher values compared to that of LEM I. The RBE-weighted tolerance dose for a 5% complication probability (TD{sub 5}) increases from 68.8 ± 3.3 to 78.3 ± 4.3 Gy (RBE) for LEM IV as compared to LEM I. Conclusions: LEM IV predicts a clinically significant increase of the RBE-weighted tolerance doses for the temporal lobe as compared to the currently applied LEM I. The limited available photon data do not allow a final conclusion as to whether RBE predictions of LEM I or LEM IV better fit better clinical experience in photon therapy. The decision about a future clinical application of LEM IV therefore requires additional analysis of temporal lobe reactions in a

  3. The Observed Variance Between Predicted and Measured Radiation Dose in Breast and Prostate Patients Utilizing an in-vivo Dosimeter

    PubMed Central

    Scarantino, Charles W.; Prestidge, Bradley R.; Anscher, Mitchel S.; Ferree, Carolyn R.; Kearns, William T.; Black, Robert D.; Bolick, Natasha G.; Beyer, Gloria P.

    2008-01-01

    Purpose Report the results of using a permanently implantable dosimeter in radiation therapy: determine specific adverse events, degree of migration, and acquire dose measurements during treatment to determine difference between expected and measured dose. Methods and Materials DVS (Dose Verification System) is a wireless, permanently implantable MOSFET dosimeter using a bidirectional antenna for power and data transfer. The study cohort includes 36 breast (33 received 2 devices) and 29 prostate (21 received 2 devices) cancer patients. A total of 1783 and 1749 daily dose measurements were obtained on breast and prostate patients, respectively. The measurements were compared to the planned expected dose. Bi-weekly CT scans were obtained to evaluate migration and NCI CTCv3 used to evaluate adverse events. Results Only grade I/II adverse events of pain and bleeding were noted. There were only four instances of dosimeter migration of >5mm due to known factors. A deviation of ≥7% in cumulative dose was noted in 7 of 36 (19%) for breast cancer patients. In prostate cancer patients, a ≥7% deviation was noted in 6 of 29 (21%) and 8 of 19 (42%) during initial and boost irradiation, respectively. The two patterns of dose deviation were random and systematic. Some causes for these differences could involve organ movement, patient movement and/or treatment plan considerations. Conclusions The DVS was not associated with significant adverse events or migration. The dosimeter can measure dose in situ on a daily basis. The accuracy and utility of the DVS complements current IGRT and IMRT techniques. PMID:18793963

  4. Dose-volumetric parameters predicting radiation-induced hepatic toxicity in unresectable hepatocellular carcinoma patients treated with three-dimensional conformal radiotherapy

    SciTech Connect

    Kim, Tae Hyun; Kim, Dae Yong . E-mail: radiopia@ncc.re.kr; Park, Joong-Won; Kim, Seong Hoon; Choi, Joon-Il; Kim, Hyun Beom; Lee, Woo Jin; Park, Sang Jae; Hong, Eun Kyung; Kim, Chang-Min

    2007-01-01

    Purpose: To identify the dose-volumetric parameters associated with the risk of radiation-induced hepatic toxicity (RIHT) in hepatocellular carcinoma patients treated with three-dimensional conformal radiotherapy. Methods and Materials: A total of 105 hepatocellular carcinoma patients underwent three-dimensional conformal radiotherapy (total dose range, 44-58.5 Gy; median, 54). RIHT was scored within 4 months of completing three-dimensional conformal radiotherapy. The dose-volume parameters analyzed were the gross tumor volume; normal liver volume; total liver volume; radiation dose; mean dose to the normal liver; percentage of the normal liver volume receiving {>=}20, {>=}25, {>=}30, {>=}35, and {>=}40 Gy; percentage of the total liver volume receiving {>=}20, {>=}25, {>=}30, {>=}35, and {>=}40 Gy; and the normal tissue complication probability. Results: Of the 105 patients, Grade 1 RIHT was observed in 21 (20.0%), Grade 2 in 7 (6.7%), Grade 3 in 5 (4.8%), and Grade 4 in 1 (1.0%) patient. No fatal Grade 5 RIHT developed. On multivariate analysis for predicting Grade 2 or worse RIHT, the total liver volume receiving {>=}30 Gy was the only significant parameter (p < 0.001). Grade 2 or worse RIHT was observed in only 2 (2.4%) of 85 patients with a total liver volume receiving 30 Gy of {<=}60% and in 11 (55.0%) of 20 patients with >60% (p < 0.001). Conclusion: The total liver volume receiving {>=}30 Gy appears to be a useful dose-volumetric parameter for predicting the risk of RIHT. This volume should be limited to {<=}60% whenever possible to minimize the risk of Grade 2 or worse RIHT.

  5. Predictive Models for Regional Hepatic Function Based upon 99mTc-IDA SPECT and Local Radiation Dose for Physiological Adaptive RT

    PubMed Central

    Wang, Hesheng; Feng, Mary; Frey, Kirk A.; Ten Haken, Randall K.; Lawrence, Theodore S.; Cao, Yue

    2013-01-01

    Purpose High dose radiation therapy (RT) for intrahepatic cancer is limited by the development of liver injury. This study investigated whether regional hepatic function assessed prior to and during the course of RT using 99mTc-labeled immindodiacetic acid (IDA) SPECT could predict regional liver function reserve after RT. Methods and Materials Fourteen patients treated with RT for intrahepatic cancers underwent dynamic 99mTc-IDA SPECT scans prior to RT, during, and one month after completion of RT. Indocyanine green (ICG) tests (a measure of overall liver function) were performed within 1 day of each scan. 3D volumetric hepatic extraction fraction (HEF) images of the liver were estimated by deconvolution analysis. After co-registration of the CT/SPECT and the treatment planning CT, HEF dose-response functions during and post-RT were generated. The volumetric mean of the HEFs in the whole liver was correlated with ICG clearance time. Three models, Dose, Priori and Adaptive models, were developed using multivariate linear regression to assess whether the regional HEFs measured before and during RT helped predict regional hepatic function post-RT. Results The mean of the volumetric liver HEFs was significantly correlated with ICG clearance half-life time (r = −0.80, p<0.0001), for all time points. Linear correlations between local doses and regional HEFs one month post-RT were significant in 12 patients. In the priori model, regional HEF post-RT was predicted by the planned dose and regional HEF assessed prior to RT (R=0.71, p<0.0001). In the adaptive model, regional HEF post-RT was predicted by regional HEF re-assessed during RT and the remaining planned local dose (R=0.83, p<0.0001). Conclusions 99mTc-IDA SPECT obtained during RT could be used to assess regional hepatic function and helped predict post-RT regional liver function reserve. This could support individualized adaptive radiation treatment strategies to maximize tumor control and minimize the risk of

  6. Pharmacokinetic/pharmacodynamic (PK/PD) indices of antibiotics predicted by a semimechanistic PKPD model: a step toward model-based dose optimization.

    PubMed

    Nielsen, Elisabet I; Cars, Otto; Friberg, Lena E

    2011-10-01

    A pharmacokinetic-pharmacodynamic (PKPD) model that characterizes the full time course of in vitro time-kill curve experiments of antibacterial drugs was here evaluated in its capacity to predict the previously determined PK/PD indices. Six drugs (benzylpenicillin, cefuroxime, erythromycin, gentamicin, moxifloxacin, and vancomycin), representing a broad selection of mechanisms of action and PK and PD characteristics, were investigated. For each drug, a dose fractionation study was simulated, using a wide range of total daily doses given as intermittent doses (dosing intervals of 4, 8, 12, or 24 h) or as a constant drug exposure. The time course of the drug concentration (PK model) as well as the bacterial response to drug exposure (in vitro PKPD model) was predicted. Nonlinear least-squares regression analyses determined the PK/PD index (the maximal unbound drug concentration [fC(max)]/MIC, the area under the unbound drug concentration-time curve [fAUC]/MIC, or the percentage of a 24-h time period that the unbound drug concentration exceeds the MIC [fT(>MIC)]) that was most predictive of the effect. The in silico predictions based on the in vitro PKPD model identified the previously determined PK/PD indices, with fT(>MIC) being the best predictor of the effect for β-lactams and fAUC/MIC being the best predictor for the four remaining evaluated drugs. The selection and magnitude of the PK/PD index were, however, shown to be sensitive to differences in PK in subpopulations, uncertainty in MICs, and investigated dosing intervals. In comparison with the use of the PK/PD indices, a model-based approach, where the full time course of effect can be predicted, has a lower sensitivity to study design and allows for PK differences in subpopulations to be considered directly. This study supports the use of PKPD models built from in vitro time-kill curves in the development of optimal dosing regimens for antibacterial drugs.

  7. TH-E-BRF-03: A Multivariate Interaction Model for Assessment of Hippocampal Vascular Dose-Response and Early Prediction of Radiation-Induced Neurocognitive Dysfunction

    SciTech Connect

    Farjam, R; Pramanik, P; Srinivasan, A; Chapman, C; Tsien, C; Lawrence, T; Cao, Y

    2014-06-15

    Purpose: Vascular injury could be a cause of hippocampal dysfunction leading to late neurocognitive decline in patients receiving brain radiotherapy (RT). Hence, our aim was to develop a multivariate interaction model for characterization of hippocampal vascular dose-response and early prediction of radiation-induced late neurocognitive impairments. Methods: 27 patients (17 males and 10 females, age 31–80 years) were enrolled in an IRB-approved prospective longitudinal study. All patients were diagnosed with a low-grade glioma or benign tumor and treated by 3-D conformal or intensity-modulated RT with a median dose of 54 Gy (50.4–59.4 Gy in 1.8− Gy fractions). Six DCE-MRI scans were performed from pre-RT to 18 months post-RT. DCE data were fitted to the modified Toft model to obtain the transfer constant of gadolinium influx from the intravascular space into the extravascular extracellular space, Ktrans, and the fraction of blood plasma volume, Vp. The hippocampus vascular property alterations after starting RT were characterized by changes in the hippocampal mean values of, μh(Ktrans)τ and μh(Vp)τ. The dose-response, Δμh(Ktrans/Vp)pre->τ, was modeled using a multivariate linear regression considering integrations of doses with age, sex, hippocampal laterality and presence of tumor/edema near a hippocampus. Finally, the early vascular dose-response in hippocampus was correlated with neurocognitive decline 6 and 18 months post-RT. Results: The μh(Ktrans) increased significantly from pre-RT to 1 month post-RT (p<0.0004). The multivariate model showed that the dose effect on Δμh(Ktrans)pre->1M post-RT was interacted with sex (p<0.0007) and age (p<0.00004), with the dose-response more pronounced in older females. Also, the vascular dose-response in the left hippocampus of females was significantly correlated with memory function decline at 6 (r = − 0.95, p<0.0006) and 18 (r = −0.88, p<0.02) months post-RT. Conclusion: The hippocampal vascular

  8. Critical Combinations of Radiation Dose and Volume Predict Intelligence Quotient and Academic Achievement Scores After Craniospinal Irradiation in Children With Medulloblastoma

    SciTech Connect

    Merchant, Thomas E.; Schreiber, Jane E.; Wu, Shengjie; Lukose, Renin; Xiong, Xiaoping; Gajjar, Amar

    2014-11-01

    Purpose: To prospectively follow children treated with craniospinal irradiation to determine critical combinations of radiation dose and volume that would predict for cognitive effects. Methods and Materials: Between 1996 and 2003, 58 patients (median age 8.14 years, range 3.99-20.11 years) with medulloblastoma received risk-adapted craniospinal irradiation followed by dose-intense chemotherapy and were followed longitudinally with multiple cognitive evaluations (through 5 years after treatment) that included intelligence quotient (estimated intelligence quotient, full-scale, verbal, and performance) and academic achievement (math, reading, spelling) tests. Craniospinal irradiation consisted of 23.4 Gy for average-risk patients (nonmetastatic) and 36-39.6 Gy for high-risk patients (metastatic or residual disease >1.5 cm{sup 2}). The primary site was treated using conformal or intensity modulated radiation therapy using a 2-cm clinical target volume margin. The effect of clinical variables and radiation dose to different brain volumes were modeled to estimate cognitive scores after treatment. Results: A decline with time for all test scores was observed for the entire cohort. Sex, race, and cerebrospinal fluid shunt status had a significant impact on baseline scores. Age and mean radiation dose to specific brain volumes, including the temporal lobes and hippocampi, had a significant impact on longitudinal scores. Dichotomized dose distributions at 25 Gy, 35 Gy, 45 Gy, and 55 Gy were modeled to show the impact of the high-dose volume on longitudinal test scores. The 50% risk of a below-normal cognitive test score was calculated according to mean dose and dose intervals between 25 Gy and 55 Gy at 10-Gy increments according to brain volume and age. Conclusions: The ability to predict cognitive outcomes in children with medulloblastoma using dose-effects models for different brain subvolumes will improve treatment planning, guide intervention, and help

  9. Predicting Dose-Response Relationships of Acute Cadmium Hepatoxicity and Metallothionein Regulation in the Rat Via In Vitro to In Vivo Extrapolation

    DTIC Science & Technology

    2006-02-01

    sensitivity to cadmium- induced hepatotoxicity in Fischer 344 and Sprague-Dawley rats . Toxicol. Sci. 67:329-40. Hoffman, E.O., Cook, J.A., DiLuzio, N.R...Vitro - In Vivo Extrapolation: Predicting Dose- Response Relationship of Acute Hepatotoxicity in the Rat (Rattus norvegicus) .............. 38 Appendix...absence of MT I and MT II has been shown to increase inorganic Cd- induced lethality and 3 hepatotoxicity , whereas gene over-expression causing

  10. Cognitive Results of CANTAB Tests and Their Change Due to the First Dose of Donepezil May Predict Treatment Efficacy in Alzheimer Disease

    PubMed Central

    Kuzmickienė, Jurgita; Kaubrys, Gintaras

    2015-01-01

    Background Ability to predict the efficacy of treatment in Alzheimer disease (AD) may be very useful in clinical practice. Cognitive predictors should be investigated alongside with the demographic, genetic, and other predictors of treatment efficacy. The aim of this study was to establish whether the baseline measures of CANTAB tests and their changes due to the first donepezil dose are able to predict the efficacy of treatment after 4 months of therapy. We also compared the predictive value of cognitive, clinical, and demographic predictors of treatment efficacy in AD. Material/Methods Seventy-two AD patients (62 treatment-naïve and 10 donepezil-treated) and 30 controls were enrolled in this prospective, randomized, rater-blinded, follow-up study. Treatment-naïve AD patients were randomized to 2 groups to take the first donepezil dose after the first or second CANTAB testing, separated by 4 hours. Follow-up Test 3 was performed 4 months after the initial assessment. Results The groups were similar in age, education, gender, Hachinski index, and depression. General Regression Models (GRM) have shown that cognitive changes after the first dose of donepezil in PAL (t-values for regression coefficients from 3.43 to 6.44), PRMd (t=4.33), SWM (t=5.85) test scores, and baseline results of PAL (t=2.57–2.86), PRM (t=3.08), and CRT (t=3.42) tests were significant predictors of long-term donepezil efficacy in AD (p<0.05). Conclusions The cognitive changes produced by the first donepezil dose in CANTAB PAL, PRM, and SWM test measures are able to predict the long-term efficacy of donepezil in AD. Baseline PAL, PRM, and CRT test results were significant predictors. PMID:26656642

  11. Cognitive Results of CANTAB Tests and Their Change Due to the First Dose of Donepezil May Predict Treatment Efficacy in Alzheimer Disease.

    PubMed

    Kuzmickienė, Jurgita; Kaubrys, Gintaras

    2015-12-14

    BACKGROUND Ability to predict the efficacy of treatment in Alzheimer disease (AD) may be very useful in clinical practice. Cognitive predictors should be investigated alongside with the demographic, genetic, and other predictors of treatment efficacy. The aim of this study was to establish whether the baseline measures of CANTAB tests and their changes due to the first donepezil dose are able to predict the efficacy of treatment after 4 months of therapy. We also compared the predictive value of cognitive, clinical, and demographic predictors of treatment efficacy in AD. MATERIAL AND METHODS Seventy-two AD patients (62 treatment-naïve and 10 donepezil-treated) and 30 controls were enrolled in this prospective, randomized, rater-blinded, follow-up study. Treatment-naïve AD patients were randomized to 2 groups to take the first donepezil dose after the first or second CANTAB testing, separated by 4 hours. Follow-up Test 3 was performed 4 months after the initial assessment. RESULTS The groups were similar in age, education, gender, Hachinski index, and depression. General Regression Models (GRM) have shown that cognitive changes after the first dose of donepezil in PAL (t-values for regression coefficients from 3.43 to 6.44), PRMd (t=4.33), SWM (t=5.85) test scores, and baseline results of PAL (t=2.57-2.86), PRM (t=3.08), and CRT (t=3.42) tests were significant predictors of long-term donepezil efficacy in AD (p<0.05). CONCLUSIONS The cognitive changes produced by the first donepezil dose in CANTAB PAL, PRM, and SWM test measures are able to predict the long-term efficacy of donepezil in AD. Baseline PAL, PRM, and CRT test results were significant predictors.

  12. Fluconazole dosing predictions in critically-ill patients receiving prolonged intermittent renal replacement therapy: a Monte Carlo simulation approach.

    PubMed

    Gharibian, Katherine N; Mueller, Bruce A

    2016-07-01

    Fluconazole is a renally-eliminated antifungal commonly used to treat Candida species infections. In critically-ill patients receiving prolonged intermittent renal replacement therapy (PIRRT), limited pharmacokinetic (PK) data are available to guide fluconazole dosing. We used previously-published fluconazole clearance data and PK data of critically-ill patients with acute kidney injury to develop a PK model with the goal of determining a therapeutic dosing regimen for critically-ill patients receiving PIRRT. Monte Carlo simulations were performed to create a virtual cohort of patients receiving different fluconazole dosing regimens. Plasma drug concentration-time profiles were evaluated on the probability of attaining a mean 24-hour area under the drug concentration-time curve to minimum inhibitory concentration ratio (AUC24h : MIC) of 100 during the initial 48 hours of antifungal therapy. At the susceptibility breakpoint of Candida albicans (2 mg/L), 93 - 96% of simulated subjects receiving PIRRT attained the pharmacodynamic target with a fluconazole 800-mg loading dose plus 400 mg twice daily (q12h or pre and post PIRRT) regimen. Monte Carlo simulations of a PK model of PIRRT provided a basis for the development of an informed fluconazole dosing recommendation when PK data was limited. This finding should be validated in the clinical setting.

  13. Prediction of radiation doses during the dismantling of the pressurized tank from emergency core cooling system of RBMK- 1500 reactor

    SciTech Connect

    Simonis, A.; Poskas, P.; Poskas, G.

    2013-07-01

    Preparation for the decommissioning of the Ignalina Nuclear Power Plant involves multiple problems. Personnel radiation safety during the performance of dismantling activities is one of them. In order to assess the optimal personnel radiation safety, the modelling is performed for large components by the means of computer code 'VISIPLAN 3D ALARA Planning tool' developed by SCK CEN (Belgium). Modelling results of radiation doses during the dismantling of the pressurized tank from the emergency core cooling system (ECCS PT) of RBMK-1500 reactor are presented in this paper. The mass of one ECCS PT is approximately 47.6 tons. The radiological surveys indicate that the inner surface of the ECCS PT is contaminated with radioactive products of corrosion and sediments due to the radioactive water. The assessment of workers exposure was performed to comply with ALARA. The effective doses to the workers were modeled for different strategies of ECCS PT dismantling. The impact of dismantling tools and shielding types and extract ventilation flow rate during the dismantling of ECCS PT on effective doses were analyzed. The total effective personnel doses were obtained by summarizing the effective personnel doses from various sources of exposure, i. e., direct radiation from radioactive equipment, internal radiation due to inhalation of radioactive aerosols, and direct radiation from radioactive aerosols arising during hot cutting in premises. (authors)

  14. Do poorer people have poorer access to local resources and facilities? The distribution of local resources by area deprivation in Glasgow, Scotland.

    PubMed

    Macintyre, Sally; Macdonald, Laura; Ellaway, Anne

    2008-09-01

    It has commonly been suggested that in modern cities individual or household deprivation (for example, low income or education) is amplified by area level deprivation (for example, lack of jobs or good schools), in ways which damage the health of the poorest and increase health inequalities. The aim of this study was to determine the location of a range of resources and exposures by deprivation in a UK city. We examined the location of 42 resources in Glasgow City, Scotland, in 2005-2006, by quintile of small area deprivation. Measures included number per 1000 population, network distance to nearest resource, and percentage of data zones containing at least one of each type of resource. Twelve resources had higher density in, and/or were closer to or more common in, more deprived neighbourhoods: public nurseries, public primary schools, police stations, pharmacies, credit unions, post offices, bus stops, bingo halls, public swimming pools, public sports centres, outdoor play areas, and vacant and derelict land/buildings. Sixteen had higher density in, and/or were closer to, or more common in, more affluent neighbourhoods: public secondary schools, private schools, banks, building societies, museums/art galleries, railway stations, subway stations, tennis courts, bowling greens, private health clubs, private swimming pools, colleges, A & E hospitals, parks, waste disposal sites, and tourist attractions. Private nurseries, Universities, fire stations, general, dental and ophthalmic practices, pawn brokers, ATMs, supermarkets, fast food chains, cafes, public libraries, golf courses, and cinemas showed no clear pattern by deprivation. Thus it appears that in the early 21st century access to resources does not always disadvantage poorer neighbourhoods in the UK. We conclude that we need to ensure that theories and policies are based on up-to-date and context-specific empirical evidence on the distribution of neighbourhood resources, and to engage in further research on

  15. Do poorer people have poorer access to local resources and facilities? The distribution of local resources by area deprivation in Glasgow, Scotland☆

    PubMed Central

    Macintyre, Sally; Macdonald, Laura; Ellaway, Anne

    2008-01-01

    It has commonly been suggested that in modern cities individual or household deprivation (for example, low income or education) is amplified by area level deprivation (for example, lack of jobs or good schools), in ways which damage the health of the poorest and increase health inequalities. The aim of this study was to determine the location of a range of resources and exposures by deprivation in a UK city. We examined the location of 42 resources in Glasgow City, Scotland, in 2005–2006, by quintile of small area deprivation. Measures included number per 1000 population, network distance to nearest resource, and percentage of data zones containing at least one of each type of resource. Twelve resources had higher density in, and/or were closer to or more common in, more deprived neighbourhoods: public nurseries, public primary schools, police stations, pharmacies, credit unions, post offices, bus stops, bingo halls, public swimming pools, public sports centres, outdoor play areas, and vacant and derelict land/buildings. Sixteen had higher density in, and/or were closer to, or more common in, more affluent neighbourhoods: public secondary schools, private schools, banks, building societies, museums/art galleries, railway stations, subway stations, tennis courts, bowling greens, private health clubs, private swimming pools, colleges, A & E hospitals, parks, waste disposal sites, and tourist attractions. Private nurseries, Universities, fire stations, general, dental and ophthalmic practices, pawn brokers, ATMs, supermarkets, fast food chains, cafes, public libraries, golf courses, and cinemas showed no clear pattern by deprivation. Thus it appears that in the early 21st century access to resources does not always disadvantage poorer neighbourhoods in the UK. We conclude that we need to ensure that theories and policies are based on up-to-date and context-specific empirical evidence on the distribution of neighbourhood resources, and to engage in further research

  16. Predictive Models for Regional Hepatic Function Based on 99mTc-IDA SPECT and Local Radiation Dose for Physiologic Adaptive Radiation Therapy

    SciTech Connect

    Wang, Hesheng; Feng, Mary; Frey, Kirk A.; Ten Haken, Randall K.; Lawrence, Theodore S.; Cao, Yue

    2013-08-01

    Purpose: High-dose radiation therapy (RT) for intrahepatic cancer is limited by the development of liver injury. This study investigated whether regional hepatic function assessed before and during the course of RT using 99mTc-labeled iminodiacetic acid (IDA) single photon emission computed tomography (SPECT) could predict regional liver function reserve after RT. Methods and Materials: Fourteen patients treated with RT for intrahepatic cancers underwent dynamic 99mTc-IDA SPECT scans before RT, during, and 1 month after completion of RT. Indocyanine green (ICG) tests, a measure of overall liver function, were performed within 1 day of each scan. Three-dimensional volumetric hepatic extraction fraction (HEF) images of the liver were estimated by deconvolution analysis. After coregistration of the CT/SPECT and the treatment planning CT, HEF dose–response functions during and after RT were generated. The volumetric mean of the HEFs in the whole liver was correlated with ICG clearance time. Three models, dose, priori, and adaptive models, were developed using multivariate linear regression to assess whether the regional HEFs measured before and during RT helped predict regional hepatic function after RT. Results: The mean of the volumetric liver HEFs was significantly correlated with ICG clearance half-life time (r=−0.80, P<.0001), for all time points. Linear correlations between local doses and regional HEFs 1 month after RT were significant in 12 patients. In the priori model, regional HEF after RT was predicted by the planned dose and regional HEF assessed before RT (R=0.71, P<.0001). In the adaptive model, regional HEF after RT was predicted by regional HEF reassessed during RT and the remaining planned local dose (R=0.83, P<.0001). Conclusions: 99mTc-IDA SPECT obtained during RT could be used to assess regional hepatic function and helped predict post-RT regional liver function reserve. This could support individualized adaptive radiation treatment strategies

  17. Hidden losers? The impact of rural refugees and refugee programs on poorer hosts.

    PubMed

    Chambers, R

    1986-01-01

    Refugee relief organizations and refugee studies have refugees as their 1st concern and focus. Adverse impacts of refugees on hosts are relatively neglected. When impacts are considered, they are seen in terms of host country governments, economies, and services rather than people or different groups among host populations. In rural refugee-affected areas, the better-off and more visible hosts usually gain from the presence of refugees and from refugee programs. In contrast, the poorer among the hosts can be hidden losers. This is more so now than in the past, especially where land is scarce and labor relatively abundant. The poorer hosts can lose from competition for food, work, wages, services, and common property resources. Vulnerable hosts also lack refugees' option of sending their weaker dependents to camps and settlements. Development programs in refugee-affected areas and refugee studies will do a disservice if they neglect adverse effects of refugees on vulnerable hosts. These effects further strengthen the case for development to benefit the whole population in refugee-affected areas (author's).

  18. PREDICTING THE ACUTE BEHAVIORAL EFFECTS OF TOLUENE INHALED FOR 24 HRS IN RATS: DOSE METRICS, METABOLISM AND BEHAVIORAL TOLERANCE

    EPA Science Inventory

    Purpose: Recent research on the acute effects of volatile organic compounds (VOCs) suggests that extrapolation from short (~ 1 h) to long durations (up to 4 h) is improved by using estimates of brain toluene concentration ( Br[ToI)] instead of cumulative inhaled dose (C x t) as a...

  19. Predicting the probability of successful efficacy of a dissociated agonist of the glucocorticoid receptor from dose-response analysis.

    PubMed

    Conrado, Daniela J; Krishnaswami, Sriram; Shoji, Satoshi; Kolluri, Sheela; Hey-Hadavi, Judith; McCabe, Dorothy; Rojo, Ricardo; Tammara, Brinda K

    2016-06-01

    PF-04171327 is a dissociated agonist of the glucocorticoid receptor (DAGR) being developed to retain anti-inflammatory efficacy while reducing unwanted effects. Our aim was to conduct a longitudinal dose-response analysis to identify the DAGR doses with efficacy similar to or greater than prednisone 10 mg once daily (QD). The data included were from a Phase 2, randomized, double-blind, parallel-group study in 323 subjects with active rheumatoid arthritis on a background of methotrexate. Subjects received DAGR 1, 5, 10 or 15 mg, prednisone 5 or 10 mg, or placebo QD for 8 weeks. The Disease Activity Score 28-4 calculated using C-Reactive Protein (DAS28-4 CRP) was the efficacy endpoint utilized in this dose-response model. For DAGR, the maximum effect (Emax) on DAS28-4 CRP was estimated to be -1.2 points (95 % CI -1.7, -0.84), and the evaluated dose range provided 31-87 % of the Emax; for prednisone 5 and 10 mg, the estimated effects were -0.27 (95 % CI -0.55, 0.006) and -0.94 point (95 % CI -1.3, -0.59), respectively. Stochastic simulations indicated that the DAGR 1, 5, 10 and 15 mg have probabilities of 0.9, 29, 54 and 62 %, respectively, to achieve efficacy greater than prednisone 10 mg at week 8. DAGR 9 mg estimated probability was 50 % suggesting that DAGR ≥9 mg QD has an effect on DAS28-4 CRP comparable to or greater than prednisone 10 mg QD. This work informs dose selection for late-stage confirmatory trials.

  20. Dominant unit CD34+ cell dose predicts engraftment after double-unit cord blood transplantation and is influenced by bank practice.

    PubMed

    Purtill, Duncan; Smith, Katherine; Devlin, Sean; Meagher, Richard; Tonon, Joann; Lubin, Marissa; Ponce, Doris M; Giralt, Sergio; Kernan, Nancy A; Scaradavou, Andromachi; Stevens, Cladd E; Barker, Juliet N

    2014-11-06

    We investigated the unit characteristics associated with engraftment after double-unit cord blood (CB) transplantation (dCBT) and whether these could be reliably identified during unit selection. Cumulative incidence of neutrophil engraftment in 129 myeloablative dCBT recipients was 95% (95% confidence interval: 90-98%). When precryopreservation characteristics were analyzed, the dominant unit CD34(+) cell dose was the only characteristic independently associated with engraftment (hazard ratio, 1.43; P = .002). When postthaw characteristics were also included, only dominant unit infused viable CD34(+) cell dose independently predicted engraftment (hazard ratio, 1.95; P < .001). We then examined the determinants of infused viable CD34(+) cell dose (precryopreservation count, postthaw recovery, and postthaw viability) in 402 units thawed at our center. This revealed close correlation between precryopreservation and postthaw CD34(+) cell counts (r(2) = 0.73). Median CD34(+) cell recovery was 101%, although it ranged from 12% to 1480%. Notably, units from non-Netcord Foundation for the Accreditation of Cellular Therapy (Netcord-FACT)-accredited banks were more likely to have low recovery (P < .001). Furthermore, although median postthaw CD34(+) cell viability was 92%, 33 (8%) units had <75% viable CD34(+) cells. Units from non-Netcord-FACT-accredited banks and units with cryovolumes other than 24.5 to 26.0 mL were more likely to have poor postthaw viability. Precryopreservation CD34(+) cell dose and banking practices should be incorporated into CB unit selection.

  1. Cervical Gross Tumor Volume Dose Predicts Local Control Using Magnetic Resonance Imaging/Diffusion-Weighted Imaging—Guided High-Dose-Rate and Positron Emission Tomography/Computed Tomography—Guided Intensity Modulated Radiation Therapy

    SciTech Connect

    Dyk, Pawel; Jiang, Naomi; Sun, Baozhou; DeWees, Todd A.; Fowler, Kathryn J.; Narra, Vamsi; Garcia-Ramirez, Jose L.; Schwarz, Julie K.; Grigsby, Perry W.

    2014-11-15

    Purpose: Magnetic resonance imaging/diffusion weighted-imaging (MRI/DWI)-guided high-dose-rate (HDR) brachytherapy and {sup 18}F-fluorodeoxyglucose (FDG) — positron emission tomography/computed tomography (PET/CT)-guided intensity modulated radiation therapy (IMRT) for the definitive treatment of cervical cancer is a novel treatment technique. The purpose of this study was to report our analysis of dose-volume parameters predicting gross tumor volume (GTV) control. Methods and Materials: We analyzed the records of 134 patients with International Federation of Gynecology and Obstetrics stages IB1-IVB cervical cancer treated with combined MRI-guided HDR and IMRT from July 2009 to July 2011. IMRT was targeted to the metabolic tumor volume and lymph nodes by use of FDG-PET/CT simulation. The GTV for each HDR fraction was delineated by use of T2-weighted or apparent diffusion coefficient maps from diffusion-weighted sequences. The D100, D90, and Dmean delivered to the GTV from HDR and IMRT were summed to EQD2. Results: One hundred twenty-five patients received all irradiation treatment as planned, and 9 did not complete treatment. All 134 patients are included in this analysis. Treatment failure in the cervix occurred in 24 patients (18.0%). Patients with cervix failures had a lower D100, D90, and Dmean than those who did not experience failure in the cervix. The respective doses to the GTV were 41, 58, and 136 Gy for failures compared with 67, 99, and 236 Gy for those who did not experience failure (P<.001). Probit analysis estimated the minimum D100, D90, and Dmean doses required for ≥90% local control to be 69, 98, and 260 Gy (P<.001). Conclusions: Total dose delivered to the GTV from combined MRI-guided HDR and PET/CT-guided IMRT is highly correlated with local tumor control. The findings can be directly applied in the clinic for dose adaptation to maximize local control.

  2. Influence of dose, cigarette smoking, age, sex, and metabolic activity on plasma clozapine concentrations: a predictive model and nomograms to aid clozapine dose adjustment and to assess compliance in individual patients.

    PubMed

    Rostami-Hodjegan, Amin; Amin, Ajmal M; Spencer, Edgar P; Lennard, Martin S; Tucker, Geoffrey T; Flanagan, Robert J

    2004-02-01

    The measurement of plasma clozapine concentrations is useful in assessing compliance, optimizing therapy, and minimizing toxicity. We measured plasma clozapine and norclozapine (N-desmethylclozapine) concentrations in samples from 3782 patients (2648 male, 1127 female). No clozapine was detected in 291 samples (227 patients, median prescribed dose 300 mg/d). In 4963 (50.2 %) samples (2222 patients); plasma clozapine concentration ranged from 10 to 350 ng/mL.Step-wise backward multiple regression analysis (37 % of the total samples) of log10 plasma clozapine concentration against log10 clozapine dose (mg/d), age (year), sex (male = 0, female = 1), cigarette smoking habit (nonsmokers = 0; smokers = 1), body weight (kg), and plasma clozapine/norclozapine ratio (clozapine metabolic ratio, MR) showed that these covariates explained 48% of the observed variation in plasma clozapine concentration (C = ng/mL x 10-3) (P < 0.001) according to the following equation: log 10 (C) = 0.811 log 10 (dose) + 0.332 (MR) + 69.42 X 10 (-3) (sex) + 2.263 x 10 (-3) (age) + 1.976 x 10(-3) (weight) - 0.171 (smoking habit) - 3.180. This model and its associated confidence intervals were used to develop nomograms of plasma clozapine concentration versus dose for male and female smokers and nonsmokers. Predicted plasma clozapine changes by +48% in nonsmokers, +17% in females, +/-8 % for every 0.1 change in MR (reference 1.32), +/-4% for every 5 years (reference 40 years), and +/-5 % for every 10 kg body weight (reference 80 kg). The nomograms can be used (i) to individualize dosage to achieve a given target plasma clozapine concentration, and (ii) for quantitative evaluation of adherence by estimating the likelihood of an observed concentration being achieved by a given dosage regimen. The model has been validated against published data.

  3. Combinatorial DNA damage pairing model based on X-ray-induced foci predicts the dose and LET dependence of cell death in human breast cells.

    PubMed

    Vadhavkar, Nikhil; Pham, Christopher; Georgescu, Walter; Deschamps, Thomas; Heuskin, Anne-Catherine; Tang, Jonathan; Costes, Sylvain V

    2014-09-01

    In contrast to the classic view of static DNA double-strand breaks (DSBs) being repaired at the site of damage, we hypothesize that DSBs move and merge with each other over large distances (μm). As X-ray dose increases, the probability of having DSB clusters increases as does the probability of misrepair and cell death. Experimental work characterizing the X-ray dose dependence of radiation-induced foci (RIF) in nonmalignant human mammary epithelial cells (MCF10A) is used here to validate a DSB clustering model. We then use the principles of the local effect model (LEM) to predict the yield of DSBs at the submicron level. Two mechanisms for DSB clustering, namely random coalescence of DSBs versus active movement of DSBs into repair domains are compared and tested. Simulations that best predicted both RIF dose dependence and cell survival after X-ray irradiation favored the repair domain hypothesis, suggesting the nucleus is divided into an array of regularly spaced repair domains of ∼1.55 μm sides. Applying the same approach to high-linear energy transfer (LET) ion tracks, we are able to predict experimental RIF/μm along tracks with an overall relative error of 12%, for LET ranging between 30-350 keV/μm and for three different ions. Finally, cell death was predicted by assuming an exponential dependence on the total number of DSBs and of all possible combinations of paired DSBs within each simulated RIF. Relative biological effectiveness (RBE) predictions for cell survival of MCF10A exposed to high-LET showed an LET dependence that matches previous experimental results for similar cell types. Overall, this work suggests that microdosimetric properties of ion tracks at the submicron level are sufficient to explain both RIF data and survival curves for any LET, similarly to the LEM assumption. Conversely, high-LET death mechanism does not have to infer linear-quadratic dose formalism as done in the LEM. In addition, the size of repair domains derived in our

  4. Combinatorial DNA Damage Pairing Model Based on X-Ray-Induced Foci Predicts the Dose and LET Dependence of Cell Death in Human Breast Cells

    SciTech Connect

    Vadhavkar, Nikhil; Pham, Christopher; Georgescu, Walter; Deschamps, Thomas; Heuskin, Anne-Catherine; Tang, Jonathan; Costes, Sylvain V.

    2014-09-01

    In contrast to the classic view of static DNA double-strand breaks (DSBs) being repaired at the site of damage, we hypothesize that DSBs move and merge with each other over large distances (m). As X-ray dose increases, the probability of having DSB clusters increases as does the probability of misrepair and cell death. Experimental work characterizing the X-ray dose dependence of radiation-induced foci (RIF) in nonmalignant human mammary epithelial cells (MCF10A) is used here to validate a DSB clustering model. We then use the principles of the local effect model (LEM) to predict the yield of DSBs at the submicron level. Two mechanisms for DSB clustering, namely random coalescence of DSBs versus active movement of DSBs into repair domains are compared and tested. Simulations that best predicted both RIF dose dependence and cell survival after X-ray irradiation favored the repair domain hypothesis, suggesting the nucleus is divided into an array of regularly spaced repair domains of ~;;1.55 m sides. Applying the same approach to high-linear energy transfer (LET) ion tracks, we are able to predict experimental RIF/m along tracks with an overall relative error of 12percent, for LET ranging between 30 350 keV/m and for three different ions. Finally, cell death was predicted by assuming an exponential dependence on the total number of DSBs and of all possible combinations of paired DSBs within each simulated RIF. Relative biological effectiveness (RBE) predictions for cell survival of MCF10A exposed to high-LET showed an LET dependence that matches previous experimental results for similar cell types. Overall, this work suggests that microdosimetric properties of ion tracks at the submicron level are sufficient to explain both RIF data and survival curves for any LET, similarly to the LEM assumption. Conversely, high-LET death mechanism does not have to infer linear-quadratic dose formalism as done in the LEM. In addition, the size of repair domains derived in our model

  5. Lesson from Canada's Universal Care: socially disadvantaged patients use more health services, still have poorer health.

    PubMed

    Alter, David A; Stukel, Therese; Chong, Alice; Henry, David

    2011-02-01

    Lower socioeconomic status is commonly related to worse health. If poor access to health care were the only explanation, universal access to care should eliminate the association. We studied 14,800 patients with access to Canada's universal health care system who were initially free of cardiac disease, tracking them for at least ten years and seven months. We found that socially disadvantaged patients used health care services more than did their counterparts with higher incomes and education. We also found that service use by people with lower incomes and less education had little impact on their poorer health outcomes, particularly mortality. Countries contemplating national health insurance cannot rely on universal health care to eliminate historical disparities in outcomes suffered by disadvantaged groups. Universal access can only reduce these disparities. Our findings suggest the need to introduce large-scale preventive strategies early in patients' lives to help change unhealthy behavior.

  6. Weekly Dose-Volume Parameters of Mucosa and Constrictor Muscles Predict the Use of Percutaneous Endoscopic Gastrostomy During Exclusive Intensity-Modulated Radiotherapy for Oropharyngeal Cancer

    SciTech Connect

    Sanguineti, Giuseppe; Gunn, G. Brandon; Parker, Brent C.; Endres, Eugene J.; Zeng Jing; Fiorino, Claudio

    2011-01-01

    Purpose: To define predictors of percutaneous endoscopic gastrostomy (PEG) use during intensity-modulated radiotherapy (IMRT) for oropharyngeal cancer. Methods and Materials: Data for 59 consecutive patients treated with exclusive IMRT at a single institution were recovered. Of 59 patients, 25 were treated with hyperfractionation (78 Gy, 1.3 Gy per fraction, twice daily; 'HYPER'); and 34 of 59 were treated with a once-daily fractionation schedule (66 Gy, 2.2 Gy per fraction, or 70 Gy, 2 Gy per fraction; 'no-HYPER'). On the basis of symptoms during treatment, a PEG tube could have been placed as appropriate. A number of clinical/dosimetric factors, including the weekly dose-volume histogram of oral mucosa (OM DVHw) and weekly mean dose to constrictors and larynx, were considered. The OM DVHw of patients with and without PEG were compared to assess the most predictive dose-volume combinations. Results: Of 59 patients, 22 needed a PEG tube during treatment (for 15 of 22, {>=}3 months). The best cutoff values for OM DVHw were V9.5 Gy/week <64 cm{sup 3} and V10 Gy/week <54 cm{sup 3}. At univariate analysis, fractionation, mean weekly dose to OM and superior and middle constrictors, and OM DVHw were strongly correlated with the risk of PEG use. In a stepwise multivariate logistic analysis, OM V9.5 Gy/week ({>=}64 vs. <64 cm{sup 3}) was the most predictive parameter (odds ratio 30.8, 95% confidence interval 3.7-254.2, p = 0.0015), confirmed even in the no-HYPER subgroup (odds ratio 21, 95% CI 2.1 confidence interval 210.1, p = 0.01). Conclusions: The risk of PEG use is drastically reduced when OM V9.5-V10 Gy/week is <50-60 cm{sup 3}. These data warrant prospective validation.

  7. Poorer breast cancer survival outcomes in males than females might be attributable to tumor subtype

    PubMed Central

    Zhu, Shan; Wu, Juan; Li, Xiang; Liu, Qian; Wei, Wen; Sun, Shengrong

    2016-01-01

    Background & Aims Substantial controversy exists regarding the differences in tumor subtypes between male breast cancer (MBC) and female breast cancer (FBC). This is the largest population-based study to compare MBC and FBC patients. Methods Using data obtained by the Surveillance, Epidemiology, and End Results (SEER) program from 2010-2012, a retrospective, population-based cohort study was conducted to investigate tumor subtype-specific differences in various characteristics, overall survival (OS) and breast cancer-specific mortality (BCSM) between males and females. Results In all, 181,814 BC patients (1,516 male and 180,298 female) were eligible for this study. The male patients were more likely to be black, older, and have lower histological grades, more advanced stages, larger tumors, more lymph node and distant metastases and human epidermal growth factor receptor 2 (HER2)-negative tumors (each p<0.05). A matched analysis showed that the 2-year OS was 91.2% and 93.7% and that the BCSM was 2.2% and 2.5% for male and female patients, respectively. The univariate analysis showed that male triple-negative (TN), hormone receptor (HoR)-positive/HER2-positive and HoR-positive/HER2-negative patients had poorer OS (p <0.01). Meanwhile, the HoR-positive/HER2-positive and TN subtypes were associated with a higher BCSM in MBC patients (p<0.01). The multivariate analysis revealed that TN MBC patients had poorer OS and BCSM (p<0.05). Simultaneously, the results showed that male patients in the HoR-positive/HER2-negative subgroup were less likely to die of BC when adjusting for other factors (p<0.05). Conclusions The analysis of 2-year OS and BCSM among the BC subtypes showed clear differences between MBC and FBC patients with the TN subtype; these differences warrant further investigation PMID:27655704

  8. Prediction of human observer performance in a 2-alternative forced choice low-contrast detection task using channelized Hotelling observer: Impact of radiation dose and reconstruction algorithms

    SciTech Connect

    Yu Lifeng; Leng Shuai; Chen Lingyun; Kofler, James M.; McCollough, Cynthia H.; Carter, Rickey E.

    2013-04-15

    Purpose: Efficient optimization of CT protocols demands a quantitative approach to predicting human observer performance on specific tasks at various scan and reconstruction settings. The goal of this work was to investigate how well a channelized Hotelling observer (CHO) can predict human observer performance on 2-alternative forced choice (2AFC) lesion-detection tasks at various dose levels and two different reconstruction algorithms: a filtered-backprojection (FBP) and an iterative reconstruction (IR) method. Methods: A 35 Multiplication-Sign 26 cm{sup 2} torso-shaped phantom filled with water was used to simulate an average-sized patient. Three rods with different diameters (small: 3 mm; medium: 5 mm; large: 9 mm) were placed in the center region of the phantom to simulate small, medium, and large lesions. The contrast relative to background was -15 HU at 120 kV. The phantom was scanned 100 times using automatic exposure control each at 60, 120, 240, 360, and 480 quality reference mAs on a 128-slice scanner. After removing the three rods, the water phantom was again scanned 100 times to provide signal-absent background images at the exact same locations. By extracting regions of interest around the three rods and on the signal-absent images, the authors generated 21 2AFC studies. Each 2AFC study had 100 trials, with each trial consisting of a signal-present image and a signal-absent image side-by-side in randomized order. In total, 2100 trials were presented to both the model and human observers. Four medical physicists acted as human observers. For the model observer, the authors used a CHO with Gabor channels, which involves six channel passbands, five orientations, and two phases, leading to a total of 60 channels. The performance predicted by the CHO was compared with that obtained by four medical physicists at each 2AFC study. Results: The human and model observers were highly correlated at each dose level for each lesion size for both FBP and IR. The

  9. Measurement and model prediction of proton-recoil track length distributions in NTA film dosimeters for neutron energy spectroscopy and retrospective dose assessment

    NASA Astrophysics Data System (ADS)

    Taulbee, Timothy D.

    The goal of this research was to determine whether neutron dose reconstruction could be improved through re-analysis of historic NTA films worn by workers in the 1950 through the 1970s. To improve neutron dose reconstruction, the underlying neutron energy spectra is critical in determining the organ dose due to energy dependence of the dose conversion factor as well as the application of radiation weighting factors used in epidemiology and probability of causation calculations. Monte Carlo models of proton-recoil track length distributions were developed and benchmarked against measurement data for both NTA and Ilford films. These models, when applied to several NTA film dosimeter configurations, demonstrated that proton-recoil track length distributions change based upon incident neutron energy. The neutron energy spectra changes that result from the general work environment such as source term and shielding can subsequently be modeled to predict the response of the NTA film dosimeter. An Automatic NTA Film Analyzer has been designed and developed to determine if the difference in proton-recoil track length distributions predicted by the Monte Carlo models could be measured and whether these differences could be correlated to the incident neutron energy spectra. The design required the development of a 2D-3D hybrid track recognition algorithm for a three dimensional analysis of the NTA film in order to accurately determine the proton-recoil track length for subsequent neutron energy determination. NTA films exposed to a plutonium fluoride (PuF4) and polonium boron (PoB) calibration sources were measured and compared. The proton-recoil track lengths were used to reconstruct the incident neutron energy spectra demonstrating the functionality of the analyzer and that reconstruction of the neutron energy spectra from NTA films is feasible. These measurements were compared to the Monte Carlo models and confirmed the applicability of using models to determine the NTA

  10. Evaluation of the Cerebral State Index in Cats under Isoflurane Anaesthesia: Dose-Effect Relationship and Prediction of Clinical Signs

    PubMed Central

    Sousa, Joana R.; Ribeiro, Lénio; Ferreira, David A.

    2014-01-01

    The performance of the cerebral state index (CSI) in reflecting different levels of isoflurane anaesthesia was evaluated in ten cats subjected to four end-tidal isoflurane concentrations (EtIso), each maintained for 15 minutes (0.8%, 1.2%, 1.6%, or 2.0% EtIso). The CSI, hemodynamic data, ocular reflexes, and eye position were recorded for each EtIso concentration. Pharmacodynamic analysis of CSI with EtIso was performed, as well as prediction probability analysis with a clinical scale based on the eye reflexes. The CSI values showed great variability. Between all parameters, burst suppression ratio showed the better fitting with the sigmoidal concentration-effect model (R2 = 0.93) followed by CSI (R2 = 0.82) and electromyographic activity (R2 = 0.79). EtIso was the variable with better prediction of the clinical scale of anaesthesia (prediction probability value of 0.94). Although the CSI values decrease with increasing isoflurane concentrations, the huge variability in CSI values may be a strong limitation for its use in cats and it seems to be no better than EtIso as a predictor of clinical signs. PMID:24616823

  11. Improved in silico prediction of carcinogenic potency (TD50) and the risk specific dose (RSD) adjusted Threshold of Toxicological Concern (TTC) for genotoxic chemicals and pharmaceutical impurities.

    PubMed

    Contrera, Joseph F

    2011-02-01

    The Threshold of Toxicological Concern (TTC) is a level of exposure to a genotoxic impurity that is considered to represent a negligible risk to humans. The TTC was derived from the results of rodent carcinogenicity TD50 values that are a measure of carcinogenic potency. The TTC currently sets a default limit of 1.5 μg/day in food contact substances and pharmaceuticals for all genotoxic impurities without carcinogenicity data. Bercu et al. (2010) used the QSAR predicted TD50 to calculate a risk specific dose (RSD) which is a carcinogenic potency adjusted TTC for genotoxic impurities. This promising approach is currently limited by the software used, a combination of MC4PC (www.multicase.com) and a Lilly Inc. in-house software (VISDOM) that is not available to the public. In this report the TD50 and RSD were predicted using a commercially available software, SciQSAR (formally MDL-QSAR, www.scimatics.com) employing the same TD50 training data set and external validation test set that was used by Bercu et al. (2010). The results demonstrate the general applicability of QSAR predicted TD50 values to determine the RSDs for genotoxic impurities and the improved performance of SciQSAR for predicting TD50 values.

  12. Prediction of the Carcinogenic Potential of Human Pharmaceuticals Using Repeated Dose Toxicity Data and Their Pharmacological Properties

    PubMed Central

    van der Laan, Jan Willem; Buitenhuis, Wenny H. W.; Wagenaar, Laura; Soffers, Ans E. M. F.; van Someren, Eugene P.; Krul, Cyrille A. M.; Woutersen, Ruud A.

    2016-01-01

    In an exercise designed to reduce animal use, we analyzed the results of rat subchronic toxicity studies from 289 pharmaceutical compounds with the aim to predict the tumor outcome of carcinogenicity studies in this species. The results were obtained from the assessment reports available at the Medicines Evaluation Board of the Netherlands for 289 pharmaceutical compounds that had been shown to be non-genotoxic. One hundred forty-three of the 239 compounds not inducing putative preneoplastic lesions in the subchronic study did not induce tumors in the carcinogenicity study [true negatives (TNs)], whereas 96 compounds were categorized as false negatives (FNs) because tumors were observed in the carcinogenicity study. Of the remaining 50 compounds, 31 showed preneoplastic lesions in the subchronic study and tumors in the carcinogenicity study [true positives (TPs)], and 19 only showed preneoplastic lesions in subchronic studies but no tumors in the carcinogenicity study [false positives (FPs)]. In addition, we then re-assessed the prediction of the tumor outcome by integrating the pharmacological properties of these compounds. These pharmacological properties were evaluated with respect to the presence or absence of a direct or indirect proliferative action. We found support for the absence of cellular proliferation for 204 compounds (TN). For 67 compounds, the presence of cellular hyperplasia as evidence for proliferative action could be found (TP). Therefore, this approach resulted in an ability to predict non-carcinogens at a success rate of 92% and the ability to detect carcinogens at 98%. The combined evaluation of pharmacological and histopathological endpoints eventually led to only 18 unknown outcomes (17 categorized as FN and 1 as FP), thereby enhancing both the negative and positive predictivity of an evaluation based upon histopathological evaluation only. The data show the added value of a consideration of the pharmacological properties of compounds in

  13. Radiation transport modeling and assessment to better predict radiation exposure, dose, and toxicological effects to human organs on long duration space flights

    NASA Technical Reports Server (NTRS)

    Denkins, P.; Badhwar, G.; Obot, V.; Wilson, B.; Jejelewo, O.

    2001-01-01

    NASA is very interested in improving its ability to monitor and forecast the radiation levels that pose a health risk to space-walking astronauts as they construct the International Space Station and astronauts that will participate in long-term and deep-space missions. Human exploratory missions to the moon and Mars within the next quarter century, will expose crews to transient radiation from solar particle events which include high-energy galactic cosmic rays and high-energy protons. Because the radiation levels in space are high and solar activity is presently unpredictable, adequate shielding is needed to minimize the deleterious health effects of exposure to radiation. Today, numerous models have been developed and used to predict radiation exposure. Such a model is the Space Environment Information Systems (SPENVIS) modeling program, developed by the Belgian Institute for Space Aeronautics. SPENVIS, which has been assessed to be an excellent tool in characterizing the radiation environment for microelectronics and investigating orbital debris, is being evaluated for its usefulness with determining the dose and dose-equivalent for human exposure. Thus far. the calculations for dose-depth relations under varying shielding conditions have been in agreement with calculations done using HZETRN and PDOSE, which are well-known and widely used models for characterizing the environments for human exploratory missions. There is disagreement when assessing the impact of secondary radiation particles since SPENVIS does a crude estimation of the secondary radiation particles when calculating LET versus Flux. SPENVIS was used to model dose-depth relations for the blood-forming organs. Radiation sickness and cancer are life-threatening consequences resulting from radiation exposure. In space. exposure to radiation generally includes all of the critical organs. Biological and toxicological impacts have been included for discussion along with alternative risk mitigation

  14. Radiation transport modeling and assessment to better predict radiation exposure, dose, and toxicological effects to human organs on long duration space flights.

    PubMed

    Denkins, P; Badhwar, G; Obot, V; Wilson, B; Jejelewo, O

    2001-01-01

    NASA is very interested in improving its ability to monitor and forecast the radiation levels that pose a health risk to space-walking astronauts as they construct the International Space Station and astronauts that will participate in long-term and deep-space missions. Human exploratory missions to the moon and Mars within the next quarter century, will expose crews to transient radiation from solar particle events which include high-energy galactic cosmic rays and high-energy protons. Because the radiation levels in space are high and solar activity is presently unpredictable, adequate shielding is needed to minimize the deleterious health effects of exposure to radiation. Today, numerous models have been developed and used to predict radiation exposure. Such a model is the Space Environment Information Systems (SPENVIS) modeling program, developed by the Belgian Institute for Space Aeronautics. SPENVIS, which has been assessed to be an excellent tool in characterizing the radiation environment for microelectronics and investigating orbital debris, is being evaluated for its usefulness with determining the dose and dose-equivalent for human exposure. Thus far. the calculations for dose-depth relations under varying shielding conditions have been in agreement with calculations done using HZETRN and PDOSE, which are well-known and widely used models for characterizing the environments for human exploratory missions. There is disagreement when assessing the impact of secondary radiation particles since SPENVIS does a crude estimation of the secondary radiation particles when calculating LET versus Flux. SPENVIS was used to model dose-depth relations for the blood-forming organs. Radiation sickness and cancer are life-threatening consequences resulting from radiation exposure. In space. exposure to radiation generally includes all of the critical organs. Biological and toxicological impacts have been included for discussion along with alternative risk mitigation

  15. Expression of HIWI in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis

    PubMed Central

    2009-01-01

    Background HIWI, the human homologue of Piwi family, is present in CD34+ hematopoietic stem cells and germ cells, but not in well-differentiated cell populations, indicating that HIWI may play an impotent role in determining or maintaining stemness of these cells. That HIWI expression has been detected in several type tumours may suggest its association with clinical outcome in cancer patients. Methods With the methods of real-time PCR, western blot, immunocytochemistry and immunohistochemistry, the expression of HIWI in three esophageal squamous cancer cell lines KYSE70, KYSE140 and KYSE450 has been characterized. Then, we investigated HIWI expression in a series of 153 esophageal squamous cell carcinomas using immunohistochemistry and explored its association with clinicopathological features. Results The expression of HIWI was observed in tumour cell nuclei or/and cytoplasm in 137 (89.5%) cases, 16 (10.5%) cases were negative in both nuclei and cytoplasm. 86 (56.2%) were strongly positive in cytoplasm, while 49 (32.0%) were strongly positive in nuclei. The expression level of HIWI in cytoplasm of esophageal cancer cells was significantly associated with histological grade (P = 0.011), T stage (P = 0.035), and clinic outcome (P < 0.001), while there was no correlation between the nuclear HIWI expression and clinicopathological features. Conclusion The expression of HIWI in the cytoplasm of esophageal cancer cells is significantly associated with higher histological grade, clinical stage and poorer clinical outcome, indicating its possible involvement in cancer development. PMID:19995427

  16. Elevated intraindividual variability in methamphetamine dependence is associated with poorer everyday functioning.

    PubMed

    Morgan, Erin E; Doyle, Katie L; Minassian, Arpi; Henry, Brook L; Perry, William; Marcotte, Thomas D; Woods, Steven Paul; Grant, Igor

    2014-12-15

    Methamphetamine (MA) dependence is associated with executive dysfunction, but no studies have evaluated MA-related elevations in neurocognitive intraindividual variability (IIV), an expression of cognitive dyscontrol linked to poor daily functioning in populations with frontal systems injury. We examined IIV during a vigilance task in a well-characterized sample of 35 MA-dependent (MA+) and 55 non-MA using comparison participants (MA-) as part of a larger neuropsychological battery that included self-report and performance-based measures of everyday functioning. A mixed model ANOVA was conducted while controlling for covariates, including factors that differed between the groups (e.g., education) and those with conceptual relevance to IIV: mean reaction time, global cognitive performance, and HIV-infection (which was comparable across groups; p=0.32). This analysis revealed significantly elevated IIV among MA+ relative to MA- individuals that was comparable in magnitude across all trial blocks of the vigilance task. Within the MA group, elevated IIV was associated with executive dysfunction, psychomotor slowing, and recency of MA use, as well as poorer automobile driving simulator performance, worse laboratory-based functional skills, and more cognitive complaints. MA-users are vulnerable to IIV elevation, likely due to cognitive dyscontrol, which may increase their risk of real-world problems.

  17. Elevated intraindividual variability in methamphetamine dependence is associated with poorer everyday functioning

    PubMed Central

    Morgan, Erin E.; Doyle, Katie L.; Minassian, Arpi; Henry, Brook; Perry, William; Marcotte, Thomas D.; Woods, Steven Paul; Grant, Igor

    2014-01-01

    Methamphetamine (MA) dependence is associated with executive dysfunction, but no studies have evaluated MA-related elevations in neurocognitive intraindividual variability (IIV), an expression of cognitive dyscontrol linked to poor daily functioning in populations with frontal systems injury. We examined IIV during a vigilance task in a well-characterized sample of 35 MA-dependent (MA+) and 55 non-MA using comparison participants (MA−) as part of a larger neuropsychological battery that included self-report and performance-based measures of everyday functioning. A mixed model ANOVA was conducted while controlling for covariates, including factors that differed between the groups (e.g., education) and those with conceptual relevance to IIV: mean reaction time, global cognitive performance, and HIV-infection (which was comparable across groups; p = .32). This analysis revealed significantly elevated IIV among MA+ relative to MA− individuals that was comparable in magnitude across all trial blocks of the vigilance task. Within the MA group, elevated IIV was associated with executive dysfunction, psychomotor slowing, and recency of MA use, as well as poorer automobile driving simulator performance, worse laboratory-based functional skills, and more cognitive complaints. MA-users are vulnerable to IIV elevation, likely due to cognitive dyscontrol, which may increase their risk of real-world problems. PMID:25081313

  18. Women's poorer satisfaction with their sex lives following gynecologic cancer treatment.

    PubMed

    Lara, Lucia Alves Silva; de Andrade, Jurandyr Moreira; Consolo, Flavio Donaire; Romão, Adriana Peterson Mariano Salata

    2012-06-01

    Gynecologic cancer treatment can lead to anatomical changes in the genitalia that may impair sexual response. As a result, the authors aimed to assess women's self-perceptions of their sex lives following gynecologic cancer treatment and the impact of such treatment on sexual function. Thirty sexually active women were examined. At the first meeting with a physician sex therapist, women were asked about their satisfaction with their sexual activities prior to and after gynecologic cancer treatment, either with a partner or alone, and how many times per month they had sexual intercourse prior to the cancer diagnosis and after treatment. Women reported significantly worse sex lives and a significantly lower frequency of sexual relations following cancer treatment. All participants reported pain on vaginal penetration and feeling uncomfortable in discussing their sexual difficulties with the oncologist. The findings show that women experienced impaired sexual function, as well as poorer quality of sexual function, following gynecologic cancer treatment. Nurses should provide basic guidelines about sexual function to all patients who undergo treatment for gynecologic cancer.

  19. Both high expression of nucleophosmin/B23 and CRM1 predicts poorer prognosis in human gastric cancer.

    PubMed

    Zhou, Fang; Chen, Ercheng; You, Dong; Song, Yipeng; Sun, Zhenni; Yue, Lu

    2016-12-01

    Nucleophosmin/B23 and CRM1 are molecular markers which play an important role in tumorigenesis and tumor progression in gastric cancer (GC). However, the association between the two remains unclear. This study evaluated the expression and the correlation of B23 and CRM1 in GC. B23 and CRM1 expression in GC and adjacent noncancerous tissues (ANCT) of gastrectomy specimens from 131 GC patients was measured by immunohistochemistry. Positive expression rates of B23 and CRM1 were significantly higher in GC tissues than in ANCT. The high expression rates of B23 and CRM1 were significantly higher in patients with more advanced tumor stages and distant metastasis (all p < 0.05). Only high expression of CRM1was correlated with positive Her2 status (p = 0.01). B23 expression was positively correlated with CRM1expression in GC tissues (p = 0.038). Univariate analysis showed that TNM stage (p = 0.0001), metastasis (p = 0.027), B23 (p = 0.0111), and CRM1 expression (p = 0.0019) were significant risk factors affecting overall survival. Both high expression of B23 and CRM1 in GC patients suggests poor prognosis, co-expression of the two (p = 0.043) even worse. Cox multivariate analysis showed that positive B23 (p = 0.0231) and CRM1 (p = 0.0048) expression were both independent prognostic factors that negatively correlated with survival. We revealed the co-expression of B23 or CRM1 in GC. The expression levels of B23 or CRM1 were closely related to poor prognosis in GC, and both B23 or CRM1 were independent risk factor.

  20. Self-Assessed Hearing Handicap in Older Adults with Poorer-than-Predicted Speech Recognition in Noise

    ERIC Educational Resources Information Center

    Eckert, Mark A.; Matthews, Lois J.; Dubno, Judy R.

    2017-01-01

    Purpose: Even older adults with relatively mild hearing loss report hearing handicap, suggesting that hearing handicap is not completely explained by reduced speech audibility. Method: We examined the extent to which self-assessed ratings of hearing handicap using the Hearing Handicap Inventory for the Elderly (HHIE; Ventry & Weinstein, 1982)…

  1. Newborn Event-Related Potentials Predict Poorer Pre-Reading Skills in Children at Risk for Dyslexia

    ERIC Educational Resources Information Center

    Guttorm, Tomi K.; Leppanen, Paavo H. T.; Hamalainen, Jarmo A.; Eklund, Kenneth M.; Lyytinen, Heikki J.

    2010-01-01

    Earlier results from the Jyvaskyla Longitudinal Study of Dyslexia showed that newborn event-related potentials (ERPs) of children with and without familial risk for dyslexia were associated with receptive language and verbal memory skills between 2.5 and 5 years of age. We further examined whether these ERPs (responses to synthetic consonant-vowel…

  2. Long intergenic non-coding RNA 271 is predictive of a poorer prognosis of papillary thyroid cancer

    PubMed Central

    Ma, Ben; Liao, Tian; Wen, Duo; Dong, Chuanpeng; Zhou, Li; Yang, Shuwen; Wang, Yu; Ji, Qinghai

    2016-01-01

    A number of long non-coding RNAs (lncRNAs) have been found to play critical roles in oncogenesis and tumor progression. We aimed to investigate whether lncRNAs could act as prognostic biomarkers for papillary thyroid cancer (PTC) that may assist us in evaluating disease status and prognosis for patients. We found 220 lncRNAs with expression alteration from the annotated 2773 lncRNAs approved by the HUGO gene nomenclature committee in The Cancer Genome Atlas (TCGA) dataset, of which FAM41C, CTBP1-AS2, LINC00271, HAR1A, LINC00310 and HAS2-AS1 were associated with recurrence. After adjusting classical clinicopathogical factors and BRAFV600E mutation, LINC00271 was found to be an independent risk factor for extrathyroidal extension, lymph node metastasis, advanced tumor stage III/IV and recurrence in multivariate analyses. Additionally, LINC00271 expression was significantly downregulated in PTCs versus adjacent normal tissues (P < 0.001). The Gene Set Enrichment Analysis (GSEA) revealed that genes associated with cell adhesion molecules, cell cycle, P53 signaling pathway and JAK/STAT signaling pathway were remarkably enriched in lower-LINC00271 versus higher-LINC00271 tumors. In conclusion, LINC00271 was identified as a possible suppressor gene in PTC in our study, and it may serve as a potential predictor of poor prognoses in PTC. PMID:27833134

  3. Adverse psychosocial factors predict poorer prognosis in HIV disease: a meta-analytic review of prospective investigations.

    PubMed

    Chida, Yoichi; Vedhara, Kavita

    2009-05-01

    There is a growing epidemiological literature focusing on the association between psychosocial stress and human immunodeficiency virus (HIV) disease progression or acquired immunodeficiency syndrome (AIDS), but inconsistent findings have been published. We aimed to quantify the association between adverse psychosocial factors and HIV disease progression. We searched Medline; PsycINFO; Web of Science; PubMed up to 19 January 2009, and included population studies with a prospective design that investigated associations between adverse psychosocial factors and HIV disease progression or AIDS. Two reviewers independently extracted data on study characteristics, quality, and estimates of associations. The overall meta-analysis examined 36 articles including 100 psychosocial and disease related relationships. It exhibited a small, but robust positive association between adverse psychosocial factors and HIV progression (correlation coefficient as combined size effect 0.059, 95% confidence interval 0.043-0.074, p<0.001). Notably, sensitivity analyses showed that personality types or coping styles and psychological distress were more strongly associated with greater HIV disease progression than stress stimuli per se, and that all of the immunological and clinical outcome indicators (acquired immunodeficiency syndrome stage, CD4+ T-cell decline, acquired immunodeficiency syndrome diagnosis, acquired immunodeficiency syndrome mortality, and human immunodeficiency virus disease or acquired immunodeficiency syndrome symptoms) except for viral load exhibited detrimental effects by adverse psychosocial factors. In conclusion, the current review reveals a robust relationship between adverse psychosocial factors and HIV disease progression. Furthermore, there would appear to be some evidence for particular psychosocial factors to be most strongly associated with HIV disease progression.

  4. Use of CFU-GM assay for prediction of human maximum tolerated dose of a new antitumoral drug: Yondelis (ET-743).

    PubMed

    Gómez, Susana G; Bueren, Juan A; Faircloth, Glynn; Albella, Beatriz

    2003-01-01

    Acute cytotoxic exposure causes decreases in bone marrow progenitors that precedes the neutrophil nadir. Experiments in animal models reveal a relationship between the reduction in granulocyte-macrophage progenitors (CFU-GM) and the decrease in absolute neutrophil count [Toxicol. Pathol. 21 (1993) 241]. Recently, the prevalidation of a model for predicting acute neutropenia by the CFU-GM assay has been reported [Toxicol. In Vitro 15 (2001) 729]. The model was based on prediction of human MTD by adjusting the animal-derived MTD for the differential sensitivity between CFU-GM from animal species and humans. In this study, this model has been applied on a new antitumoral drug, Yondelis (Ecteinascidin; ET-743). Preclinical studies showed that hematotoxicity was the main side effect in mice, being the MTD of 600 microg/m2 [Drugs Future 21 (1996) 1155]. The sensitivity of myeloid progenitors was higher in mice than in humans, with IC90 values of 0.69+/-0.22 nM and 1.31+/-0.21 nM for murine and human CFU-GMs respectively. This study predicts a human MTD of 1145 microg/m2. The reported human MTD of ET-743 given as a 24-h continuous infusion every 3 weeks is 1800 microg/m2 [J. Clin. Oncol. 19 (2001) 1256]. Since our predicted MTD is within fourfold of the actual MTD (the interspecies variation in tolerated dose due to differences in clearance rates, metabolism pathways and infusion rate) the result confirms the profit of the prediction model.

  5. Predicting of Effective Dose as Biomarker for Cytotoxicity Using Partial Least Square-Fourier Transform Infrared Spectroscopy (PLS_FTIR).

    PubMed

    Zendehdel, Rezvan; Khodakarim, Soheila; H Shirazi, Farshad

    2015-01-01

    Toxicity bioassays are important tools to determine biological effects of chemical agents on species. The questions remained on, what effects have been imposed on each of the different molecular site of cells by chemical exposure and how to find a pattern for chemical toxicity. To address the questions, HepG2 cell lines were exposed to the different concentrations of cisplatin for 24 hours to result cell mortality in the range of one to one hundred percent. Fourier Transform Infrared spectroscopy (FTIR) has been used in this study to analyze the chemical alterations on HepG2 cell line by cisplatin. Partial least square regression (PLS) analysis was then applied to the FTIR spectrum results to search for a biomarker peak and present the desire cellular effects of cisplatin. The comparison of cellular FTIR spectra after exposure to different concentrations of cisplatin confirmed the binding of cisplatin to DNA through direct interaction of platinum to guanine and thymine bases of DNA. Biochemical Index Spectra (BIS) were defined based on the differences between of normal and cisplatin exposed cells. Information from the BIS was subjected to PLS analysis to trigger any particular relationship between the toxicity spectral response and cisplatin concentration. This approach was capable of predicting the concentration of cisplatin for any particular effects observed in the cellular FTIR spectrum (R(2) = 0.968 ± 0.037). Our work supports the promises that, FTIR can demonstrate the trace of toxicity before the cells dies. Finally, PLS of FTIR data directly predicts the effective concentration of chemicals in particular cellular components.

  6. Superoxide radical-generating compounds activate a predicted promoter site for paraquat-inducible genes of the Chromobacterium violaceum bacterium in a dose-dependent manner.

    PubMed

    Gabriel, J E; Guerra-Slompo, E P; de Souza, E M; de Carvalho, F A L; Madeira, H M F; de Vasconcelos, A T R

    2015-08-21

    The purpose of the present study was to functionally evaluate the influence of superoxide radical-generating compounds on the heterologous induction of a predicted promoter region of open reading frames for paraquat-inducible genes (pqi genes) revealed during genome annotation analyses of the Chromobacterium violaceum bacterium. A 388-bp fragment corresponding to a pqi gene promoter of C. violaceum was amplified using specific primers and cloned into a conjugative vector containing the Escherichia coli lacZ gene without a promoter. Assessments of the expression of the β-galactosidase enzyme were performed in the presence of menadione (MEN) and phenazine methosulfate (PMS) compounds at different final concentrations to evaluate the heterologous activation of the predicted promoter region of interest in C. violaceum induced by these substrates. Under these experimental conditions, the MEN reagent promoted highly significant increases in the expression of the β-galactosidase enzyme modulated by activating the promoter region of the pqi genes at all concentrations tested. On the other hand, significantly higher levels in the expression of the β-galactosidase enzyme were detected exclusively in the presence of the PMS reagent at a final concentration of 50 μg/mL. The findings described in the present study demonstrate that superoxide radical-generating compounds can activate a predicted promoter DNA motif for pqi genes of the C. violaceum bacterium in a dose-dependent manner.

  7. Ratios of T lymphocyte subpopulations predict survival of cadaveric renal allografts in adult patients on low dose corticosteroid therapy.

    PubMed

    Van Es, A; Tanke, H J; Baldwin, W M; Oljans, P J; Ploem, J S; Vanes, L A

    1983-04-01

    Peripheral blood T lymphocyte subpopulations were monitored in 45 consecutive adult recipients of cadaveric renal allografts by using monoclonal antibodies and flow cytometrie. All patients were treated with low dose corticosteroids and azathioprine. In 37 patients pre-transplant OKT4/OKT8 ratios were available. Six of 26 patients (23%) with pre-transplant OKT4/OKT8 ratios greater than 1.6 and seven of 11 patients (64%) with pre-transplant OKT4/OKT8 ratio less than or equal to 1.6 lost their graft due to rejection within 6 months. The difference in transplant survival between patients with pre-transplant OKT4/OKT8 ratios greater than 1.6 and less than or equal to 1.6i is just significant (P = 0 . 049 Fishers test). No correlation was found between post-transplant values of individual lymphocyte subpopulations or OKT4/OKT8 ratios and the incidence of subsequent rejection episodes. Forty out of 45 patients suffered one or more rejection episodes which were treated by raising the dosage of prednisone. In 24 of these patients the rejection episode was reversed, leading to a transplant survival of at least 6 months. In these 24 patients the OKT4/OKT8 ratio was greater than 1.6 for at least 3 days before the institution of any rejection treatments. Sixteen patients lost their graft due to rejection within 6 months after transplantation. In 11 of these 16 patients OKT4/OKT8 ratios less than or equal to 1.6 preceded the institution of all rejection treatments for at least 3 days, while in three patients the OKT4/OKT8 ratio was greater than 1.6 before the first rejection episode but this ratio was less than or equal to 1.6 before subsequent rejection episodes. Thus, OKT4/OKT8 ratios greater than 1.i6 correlated with reversible rejection episodes and OKT4/OKT8 ratios less than or equal to 1.6 correlated with irreversible rejection (P less than 0 . 001).

  8. Initial misdiagnosis of melanoma located on the foot is associated with poorer prognosis.

    PubMed

    Sondermann, Wiebke; Zimmer, Lisa; Schadendorf, Dirk; Roesch, Alexander; Klode, Joachim; Dissemond, Joachim

    2016-07-01

    Acral melanoma has been reported to be associated with poorer outcomes than melanoma occurring on other cutaneous sites. It has been suggested that part of this disparity in outcomes may be related to delay in diagnosis. Therefore, we have analyzed the rate of misdiagnoses in patients with melanoma located on the foot and have characterized the influence on the clinical course and survival of the patients. A prospective, computerized melanoma database at the Skin Cancer Center of the University Hospital Essen, Germany was used to identify patients with histologically confirmed melanoma located on the foot between 2002 and July 2013 for subsequent analysis. A cohort of 151 patients diagnosed with primary melanoma located on the foot was identified. One hundred seven patients qualified for subsequent analysis. Forty-two patients were male (39.3%) and 65 (60.7%) were female; the mean age at first diagnosis was 61.6 years (median 66 years). The youngest patient was 19 years, the oldest 88 years old.Of the 107 patients analyzed, 32 (30%) were initially misdiagnosed. Misdiagnoses included chronic wounds, nevi, hematoma, fungal infections, warts, and paronychia. Misdiagnosis caused a median delay in diagnosis of 9 months. The 5-year disease-free survival rate (47.8% vs 72.7%) and the 5-year overall survival rate (63.5% vs 88.4%) were statistically significant lower in the misdiagnosis cohort.The awareness of potentially overlooked melanoma located on the foot has to increase among physicians.To improve early detection and, thus, the prognosis of patients with melanoma located on the foot, taking a biopsy from any suspicious lesion should be taken into consideration as soon as possible.

  9. Poorer Prognosis of Primary Signet-Ring Cell Carcinoma of the Breast Compared with Mucinous Carcinoma

    PubMed Central

    Lin, Qingzhong; Chen, Gang; Lu, Jianping; Zeng, Yi; Hu, Dan; Huang, Kai; Lin, Zhiwu; Yan, Jun

    2016-01-01

    Primary signet-ring cell carcinoma (PSRCC) of the breast is a rare entity and classified under mucin producing tumors in the WHO classification. However, little is known about the clinicopathological characteristics and clinical outcomes of PSRCC as opposed to mucinous carcinoma. Eleven patients with PSRCC in our center from 1995 to 2010 were evaluated in this study, as compared to 50 cases of mucinous breast cancer (MBC) during the same period. The clinicopathologic features of PSRCC compared to MBC were assessed. Furthermore, overall survival (OS) and disease-free survival (DFS) were calculated at 5 years of follow up. Patients with PSRCC showed more frequent lymphatic metastasis, higher Ki67 labeling index and more advanced stage disease than that of MBC (P = 0.018, p = 0.023, P = 0.000, respectively), although there was no difference in age, tumor size, and ER, PR expression between PSRCC and MBC. In addition, PSRCC was associated with simultaneous vimentin upregulation and E-cadherin downregulation. The 5-year OS of PSRCC (54.5%) was significantly lower than that of MBC (88%) (P = 0.004). Similarly, the DFS of PSRCC was poorer than that of MBC significantly (5-year DFS: 27.3% vs. 80%, P = 0.000). Conclusions Our results confirmed the more aggressive behavior of PSRCC compared to MBC. This tumor is frequently associated with more frequent lymphatic metastasis, higher Ki67 labeling index, more advanced stage disease as well as simultaneous vimentin upregulation and E-cadherin downregulation. Different management guidelines should be considered for the two types. PMID:27583684

  10. Initial misdiagnosis of melanoma located on the foot is associated with poorer prognosis

    PubMed Central

    Sondermann, Wiebke; Zimmer, Lisa; Schadendorf, Dirk; Roesch, Alexander; Klode, Joachim; Dissemond, Joachim

    2016-01-01

    Abstract Acral melanoma has been reported to be associated with poorer outcomes than melanoma occurring on other cutaneous sites. It has been suggested that part of this disparity in outcomes may be related to delay in diagnosis. Therefore, we have analyzed the rate of misdiagnoses in patients with melanoma located on the foot and have characterized the influence on the clinical course and survival of the patients. A prospective, computerized melanoma database at the Skin Cancer Center of the University Hospital Essen, Germany was used to identify patients with histologically confirmed melanoma located on the foot between 2002 and July 2013 for subsequent analysis. A cohort of 151 patients diagnosed with primary melanoma located on the foot was identified. One hundred seven patients qualified for subsequent analysis. Forty-two patients were male (39.3%) and 65 (60.7%) were female; the mean age at first diagnosis was 61.6 years (median 66 years). The youngest patient was 19 years, the oldest 88 years old. Of the 107 patients analyzed, 32 (30%) were initially misdiagnosed. Misdiagnoses included chronic wounds, nevi, hematoma, fungal infections, warts, and paronychia. Misdiagnosis caused a median delay in diagnosis of 9 months. The 5-year disease-free survival rate (47.8% vs 72.7%) and the 5-year overall survival rate (63.5% vs 88.4%) were statistically significant lower in the misdiagnosis cohort. The awareness of potentially overlooked melanoma located on the foot has to increase among physicians. To improve early detection and, thus, the prognosis of patients with melanoma located on the foot, taking a biopsy from any suspicious lesion should be taken into consideration as soon as possible. PMID:27442685

  11. Pretransplant transcriptome profiles identify among kidneys with delayed graft function those with poorer quality and outcome.

    PubMed

    Mas, Valeria R; Scian, Mariano J; Archer, Kellie J; Suh, Jihee L; David, Krystle G; Ren, Qing; Gehr, Todd W B; King, Anne L; Posner, Marc P; Mueller, Thomas F; Maluf, Daniel G

    2011-01-01

    Robust biomarkers are needed to identify donor kidneys with poor quality associated with inferior early and longer-term outcome. The occurrence of delayed graft function (DGF) is most often used as a clinical outcome marker to capture poor kidney quality. Gene expression profiles of 92 preimplantation biopsies were evaluated in relation to DGF and estimated glomerular filtration rate (eGFR) to identify preoperative gene transcript changes associated with short-term function. Patients were stratified into those who required dialysis during the first week (DGF group) versus those without (noDGF group) and subclassified according to 1-month eGFR of >45 mL/min (eGFR(hi)) versus eGFR of ≤45 mL/min (eGFR(lo)). The groups and subgroups were compared in relation to clinical donor and recipient variables and transcriptome-associated biological pathways. A validation set was used to confirm target genes. Donor and recipient characteristics were similar between the DGF versus noDGF groups. A total of 206 probe sets were significant between groups (P < 0.01), but the gene functional analyses failed to identify any significantly affected pathways. However, the subclassification of the DGF and noDGF groups identified 283 probe sets to be significant among groups and associated with biological pathways. Kidneys that developed postoperative DGF and sustained an impaired 1-month function (DGF(lo) group) showed a transcriptome profile of significant immune activation already preimplant. In addition, these kidneys maintained a poorer transplant function throughout the first-year posttransplant. In conclusion, DGF is a poor marker for organ quality and transplant outcome. In contrast, preimplant gene expression profiles identify "poor quality" grafts and may eventually improve organ allocation.

  12. Hyper-responsiveness to acute stress, emotional problems and poorer memory in former preterm children.

    PubMed

    Quesada, Andrea A; Tristão, Rosana M; Pratesi, Riccardo; Wolf, Oliver T

    2014-09-01

    The prevalence of preterm birth (PTB) is high worldwide, especially in developing countries like Brazil. PTB is marked by a stressful environment in intra- as well as extrauterine life, which can affect neurodevelopment and hormonal and physiological systems and lead to long-term negative outcomes. Nevertheless, little is known about PTB and related outcomes later on in childhood. Thus, the goals of the current study were threefold: (1) comparing cortisol and alpha-amylase (sAA) profiles, including cortisol awakening response (CAR), between preterm and full-term children; (2) evaluating whether preterm children are more responsive to acute stress and (3) assessing their memory skills and emotional and behavioral profiles. Basal cortisol and sAA profiles, including CAR of 30 preterm children, aged 6 to 10 years, were evaluated. Further, we assessed memory functions using the Wide Range Assessment of Memory and Learning, and we screened behavior/emotion using the Strengths and Difficulties Questionnaire. The results of preterm children were compared to an age- and sex-matched control group. One week later, participants were exposed to a standardized laboratory stressor [Trier Social Stress Test for Children (TSST-C)], in which cortisol and sAA were measured at baseline, 1, 10 and 25 min after stressor exposure. Preterm children had higher cortisol concentrations at awakening, a flattened CAR and an exaggerated response to TSST-C compared to full-term children. These alterations were more pronounced in girls. In addition, preterm children were characterized by more emotional problems and poorer memory performance. Our findings illustrate the long-lasting and in part sex-dependent effects of PTB on the hypothalamic-pituitary-adrenal (HPA) axis, internalizing behavior and memory. The findings are in line with the idea that early adversity alters the set-point of the HPA axis, thereby creating a more vulnerable phenotype.

  13. Prognostic relevance of DHAP dose-density in relapsed Hodgkin lymphoma: an analysis of the German Hodgkin-Study Group.

    PubMed

    Sasse, Stephanie; Alram, Magdalena; Müller, Horst; Smardová, Lenka; Metzner, Bernd; Doehner, Hartmut; Fischer, Thomas; Niederwieser, Dietger W; Schmitz, Norbert; Schäfer-Eckart, Kerstin; Raemaekers, John M M; Schmalz, Oliver; Tresckow, Bastian V; Engert, Andreas; Borchmann, Peter

    2016-05-01

    Only 50% of patients with relapsed Hodgkin lymphoma (HL) can be cured with intensive induction chemotherapy, followed by high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT). Based on the results of the HDR2 trial two courses of DHAP and subsequent HDCT/ASCT are the current standard of care in relapsed HL. In order to assess the prognostic relevance of DHAP dose density, we performed a retrospective multivariate analysis of the HDR2 trial (N=266). In addition to four risk factors (early or multiple relapse, stage IV disease or anemia at relapse, and grade IV hematotoxicity during the first cycle of DHAP) a delayed start of the second cycle of DHAP>day 22 predicted a significantly poorer progression-free survival (PFS, p=0.0356) and overall survival (OS, p=0.0025). In conclusion, our analysis strongly suggests that dose density of DHAP has a relevant impact on the outcome of relapsed HL patients.

  14. A Novel Method for Predicting Late Genitourinary Toxicity After Prostate Radiation Therapy and the Need for Age-Based Risk-Adapted Dose Constraints

    SciTech Connect

    Ahmed, Awad A.; Egleston, Brian; Alcantara, Pino; Li, Linna; Pollack, Alan; Horwitz, Eric M.; Buyyounouski, Mark K.

    2013-07-15

    Background: There are no well-established normal tissue sparing dose–volume histogram (DVH) criteria that limit the risk of urinary toxicity from prostate radiation therapy (RT). The aim of this study was to determine which criteria predict late toxicity among various DVH parameters when contouring the entire solid bladder and its contents versus the bladder wall. The area under the histogram curve (AUHC) was also analyzed. Methods and Materials: From 1993 to 2000, 503 men with prostate cancer received 3-dimensional conformal RT (median follow-up time, 71 months). The whole bladder and the bladder wall were contoured in all patients. The primary endpoint was grade ≥2 genitourinary (GU) toxicity occurring ≥3 months after completion of RT. Cox regressions of time to grade ≥2 toxicity were estimated separately for the entire bladder and bladder wall. Concordance probability estimates (CPE) assessed model discriminative ability. Before training the models, an external random test group of 100 men was set aside for testing. Separate analyses were performed based on the mean age (≤ 68 vs >68 years). Results: Age, pretreatment urinary symptoms, mean dose (entire bladder and bladder wall), and AUHC (entire bladder and bladder wall) were significant (P<.05) in multivariable analysis. Overall, bladder wall CPE values were higher than solid bladder values. The AUHC for bladder wall provided the greatest discrimination for late bladder toxicity when compared with alternative DVH points, with CPE values of 0.68 for age ≤68 years and 0.81 for age >68 years. Conclusion: The AUHC method based on bladder wall volumes was superior for predicting late GU toxicity. Age >68 years was associated with late grade ≥2 GU toxicity, which suggests that risk-adapted dose constraints based on age should be explored.

  15. Radiation Transport Modeling and Assessment to Better Predict Radiation Exposure, Dose, and Toxicological Effects to Human Organs on Long Duration Space Flights

    NASA Technical Reports Server (NTRS)

    Denkins, Pamela; Badhwar, Gautam; Obot, Victor

    2000-01-01

    NASA's long-range plans include possible human exploratory missions to the moon and Mars within the next quarter century. Such missions beyond low Earth orbit will expose crews to transient radiation from solar particle events which include high-energy galactic cosmic rays and high-energy protons. Because the radiation levels in space are high and the missions long, adequate shielding is needed to minimize the deleterious health effects of exposure to radiation. The focus of this study is radiation exposure to the blood-forming organs of the NASA astronauts. NASA/JSC developed the Phantom Torso Experiment for Organ Dose Measurements which housed active and passive dosimeters that would monitor and record absorbed radiation levels at vital organ locations. This experiment was conducted during the STS-9 I mission in May '98 and provided the necessary space radiation data for correlation to results obtained from the current analytical models used to predict exposure to the blood-forming organs. Numerous models (i.e., BRYNTRN and HZETRN) have been developed and used to predict radiation exposure. However, new models are continually being developed and evaluated. The Space Environment Information Systems (SPENVIS) modeling program, developed by the Belgian Institute for Space Aeronomy, is to be used and evaluated as a part of the research activity. It is the intent of this research effort to compare the modeled data to the findings from the STS-9 I mission; assess the accuracy and efficiency of this model; and to determine its usefulness for predicting radiation exposure and developing better guidelines for shielding requirements for long duration manned missions.

  16. The use of in vitro toxicity data and physiologically based kinetic modeling to predict dose-response curves for in vivo developmental toxicity of glycol ethers in rat and man.

    PubMed

    Louisse, Jochem; de Jong, Esther; van de Sandt, Johannes J M; Blaauboer, Bas J; Woutersen, Ruud A; Piersma, Aldert H; Rietjens, Ivonne M C M; Verwei, Miriam

    2010-12-01

    At present, regulatory assessment of systemic toxicity is almost solely carried out using animal models. The European Commission's REACH legislation stimulates the use of animal-free approaches to obtain information on the toxicity of chemicals. In vitro toxicity tests provide in vitro concentration-response curves for specific target cells, whereas in vivo dose-response curves are regularly used for human risk assessment. The present study shows an approach to predict in vivo dose-response curves for developmental toxicity by combining in vitro toxicity data and in silico kinetic modeling. A physiologically based kinetic (PBK) model was developed, describing the kinetics of four glycol ethers and their embryotoxic alkoxyacetic acid metabolites in rat and man. In vitro toxicity data of these metabolites derived in the embryonic stem cell test were used as input in the PBK model to extrapolate in vitro concentration-response curves to predicted in vivo dose-response curves for developmental toxicity of the parent glycol ethers in rat and man. The predicted dose-response curves for rat were found to be in concordance with the embryotoxic dose levels measured in reported in vivo rat studies. Therefore, predicted dose-response curves for rat could be used to set a point of departure for deriving safe exposure limits in human risk assessment. Combining the in vitro toxicity data with a human PBK model allows the prediction of dose-response curves for human developmental toxicity. This approach could therefore provide a means to reduce the need for animal testing in human risk assessment practices.

  17. Von Willebrand Factor Antigen Predicts Response to Double Dose of Aspirin and Clopidogrel by PFA-100 in Patients Undergoing Primary Angioplasty for St Elevation Myocardial Infarction

    PubMed Central

    Gianetti, Jacopo; Parri, Maria Serena; Della Pina, Francesca; Marchi, Federica; Koni, Endrin; De Caterina, Alberto; Maffei, Stefano

    2013-01-01

    Von Willebrand factor (VWF) is an emerging risk factor in acute coronary syndromes. Platelet Function Analyzer (PFA-100) with Collagen/Epinephrine (CEPI) is sensitive to functional alterations of VWF and also identifies patients with high on-treatment platelet reactivity (HPR). The objective of this study was to verify the effect of double dose (DD) of aspirin and clopidogrel on HPR detected by PFA-100 and its relation to VWF and to its regulatory metalloprotease ADAMTS-13. Between 2009 and 2011 we enrolled 116 consecutive patients with ST elevation myocardial infarction undergoing primary PCI with HPR at day 5 after PCI. Patients recruited were then randomized between a standard dose (SD, n = 58) or DD of aspirin and clopidogrel (DD, n = 58), maintained for 6 months follow-up. Blood samples for PFA-100, light transmittance aggregometry, and VWF/ADAMTS-13 analysis were collected after 5, 30, and 180 days (Times 0, 1, and 2). At Times 1 and 2 we observed a significantly higher CEPI closure times (CT) in DD as compared to SD (P < 0.001). Delta of CEPI-CT (T1 − T0) was significantly related to VWF (P < 0.001) and inversely related to ADAMTS-13 (0.01). Responders had a significantly higher level of VWF at T0. Finally, in a multivariate model analysis, VWF and ADAMTS-13 in resulted significant predictors of CEPI-CT response (P = 0.02). HRP detected by PFA-100 in acute myocardial infarction is reversible by DD of aspirin and clopidogrel; the response is predicted by basal levels of VWF and ADAMTS-13. PFA-100 may be a useful tool to risk stratification in acute coronary syndromes given its sensitivity to VWF. PMID:24453831

  18. Integration of the predictions of two models with dose measurements in a case study of children exposed to the emissions of a lead smelter

    SciTech Connect

    Bonnard, R.; McKone, T.E.

    2009-03-01

    The predictions of two source-to-dose models are systematically evaluated with observed data collected in a village polluted by a currently operating secondary lead smelter. Both models were built up from several sub-models linked together and run using Monte-Carlo simulation, to calculate the distribution children's blood lead levels attributable to the emissions from the facility. The first model system is composed of the CalTOX model linked to a recoded version of the IEUBK model. This system provides the distribution of the media-specific lead concentrations (air, soil, fruit, vegetables and blood) in the whole area investigated. The second model consists of a statistical model to estimate the lead deposition on the ground, a modified version of the model HHRAP and the same recoded version of the IEUBK model. This system provides an estimate of the concentration of exposure of specific individuals living in the study area. The predictions of the first model system were improved in terms of accuracy and precision by performing a sensitivity analysis and using field data to correct the default value provided for the leaf wet density. However, in this case study, the first model system tends to overestimate the exposure due to exposed vegetables. The second model was tested for nine children with contrasting exposure conditions. It managed to capture the blood levels for eight of them. In the last case, the exposure of the child by pathways not considered in the model may explain the failure of the model. The interest of this integrated model is to provide outputs with lower variance than the first model system, but at the moment further tests are necessary to conclude about its accuracy.

  19. First month prednisone dose predicts prednisone burden during the following 11 months: an observational study from the RELES cohort

    PubMed Central

    Ruiz-Irastorza, G; Garcia, M; Espinosa, G; Caminal, L; Mitjavila, F; González-León, R; Sopeña, B; Canora, J; Villalba, M V; Rodríguez-Carballeira, M; López-Dupla, J M; Callejas, J L; Castro, A; Tolosa, C; Sánchez-García, M E; Pérez-Conesa, M; Navarrete-Navarrete, N; Rodríguez, A P; Herranz, M T; Pallarés, L

    2016-01-01

    Aim To study the influence of prednisone dose during the first month after systemic lupus erythematosus (SLE) diagnosis (prednisone-1) on glucocorticoid burden during the subsequent 11 months (prednisone-2–12). Methods 223 patients from the Registro Español de Lupus Eritematoso Sistémico inception cohort were studied. The cumulative dose of prednisone-1 and prednisone-2–12 were calculated and recoded into a four-level categorical variable: no prednisone, low dose (up to 7.5 mg/day), medium dose (up to 30 mg/day) and high dose (over 30 mg/day). The association between the cumulative prednisone-1 and prednisone-2–12 doses was tested. We analysed whether the four-level prednisone-1 categorical variable was an independent predictor of an average dose >7.5 mg/day of prednisone-2–12. Adjusting variables included age, immunosuppressives, antimalarials, methyl-prednisolone pulses, lupus nephritis and baseline SLE Disease Activity Index (SLEDAI). Results Within the first month, 113 patients (51%) did not receive any prednisone, 24 patients (11%) received average low doses, 46 patients (21%) received medium doses and 40 patients (18%) received high doses. There was a strong association between prednisone-1 and prednisone-2–12 dose categories (p<0.001). The cumulative prednisone-1 dose was directly associated with the cumulative prednisone-2–12 dose (p<0.001). Compared with patients on no prednisone, patients taking medium (adjusted OR 5.27, 95% CI 2.18 to 12.73) or high-dose prednisone-1 (adjusted OR 10.5, 95% CI 3.8 to 29.17) were more likely to receive prednisone-2–12 doses of >7.5 mg/day, while patients receiving low-dose prednisone-1 were not (adjusted OR 1.4, 95% CI 0. 0.38 to 5.2). If the analysis was restricted to the 158 patients with a baseline SLEDAI of ≥6, the model did not change. Conclusion The dose of prednisone during the first month after the diagnosis of SLE is an independent predictor of prednisone burden during the following

  20. Circulating immune cell phenotype can predict the outcome of lenalidomide plus low-dose dexamethasone treatment in patients with refractory/relapsed multiple myeloma.

    PubMed

    Lee, Sung-Eun; Lim, Ji-Young; Ryu, Da-Bin; Kim, Tae Woo; Yoon, Jae-Ho; Cho, Byung-Sik; Eom, Ki-Seong; Kim, Yoo-Jin; Kim, Hee-Je; Lee, Seok; Cho, Seok-Goo; Kim, Dong-Wook; Lee, Jong-Wook; Min, Woo-Sung; Kim, Myungshin; Min, Chang-Ki

    2016-08-01

    Although the antimyeloma effect of lenalidomide is associated with activation of the immune system, the exact in vivo immunomodulatory mechanisms of lenalidomide combined with low-dose dexamethasone (Len-dex) in refractory/relapsed multiple myeloma (RRMM) patients remain unclear. In this study, we analyzed the association between immune cell populations and clinical outcomes in patients receiving Len-dex for the treatment of RRMM. Peripheral blood samples from 90 RRMM patients were taken on day 1 of cycles 1 (baseline), 2, 3, and 4 of Len-dex therapy. Peripheral blood CD3(+), CD4(+), and CD8(+) cell frequencies were significantly decreased by 3 cycles of therapy, whereas NK cell frequency was significantly increased after the 3rd cycle. For the myeloid-derived suppressor cell (MDSC) subset, the frequency of granulocytic MDSCs transiently increased after the 1st cycle, whereas there was an increase in monocytic MDSC (M-MDSC) frequency after the 1st and 3rd cycles. Among 81 evaluable patients, failure to achieve a response of VGPR or greater was associated with a decrease in CD8(+) cell frequency and increase in M-MDSC frequency after 3 cycles of Len-dex treatment. A high proportion of natural killer T (NKT)-like cells (CD3(+)/CD56(+)) prior to Len-dex treatment might predict a longer time to progression. In addition, patients with a smaller decrease in the frequency of both CD3(+) cells and CD8(+) cells by 3 cycles exhibited a longer time to the next treatment. These results demonstrated that early changes in immune cell subsets are useful immunologic indicators of the efficacy of Len-dex treatment in RRMM.

  1. Poorer Subjective Sleep Quality Is Related to Higher Fantasy-Induced Sexual Arousal in Women of Reproductive Age.

    PubMed

    Costa, Rui M; Oliveira, Tânia F

    2016-11-16

    Lack of sleep enhances erections and lubrication the next day. This raises the possibility that poorer subjective sleep quality is related to sexual arousal. To test this hypothesis, sexual arousal was elicited in 70 Portuguese women of reproductive age by means of fantasy. The level of salivary testosterone before and shortly after fantasy was determined by luminescence immunoassays. Participants completed the Pittsburgh Sleep Quality Index (PSQI), reported their sexual arousal before and during fantasy, and how anxious they were after the fantasy. The hypothesis was confirmed. Anxiety did not explain the association, but testosterone response (poststimulus minus baseline) had a slight explanatory effect.

  2. SHEDS-PM: A POPULATION EXPOSURE MODEL FOR PREDICTING DISTRIBUTIONS OF PM EXPOSURE AND DOSE FROM BOTH OUTDOOR AND INDOOR SOURCES

    EPA Science Inventory

    The US EPA National Exposure Research Laboratory (NERL) has developed a population exposure and dose model for particulate matter (PM), called the Stochastic Human Exposure and Dose Simulation (SHEDS) model. SHEDS-PM uses a probabilistic approach that incorporates both variabi...

  3. Schizotypal Traits are Associated with Poorer Executive Functioning in Healthy Adults

    PubMed Central

    Louise, Stephanie; Gurvich, Caroline; Neill, Erica; Tan, Eric J.; Van Rheenen, Tamsyn E.; Rossell, Susan

    2015-01-01

    Previous research has shown mild forms of the neurocognitive impairments seen in schizophrenia among healthy individuals exhibiting high schizotypal traits. This study aimed to explore associations between schizotypy and cognitive performance in an adult community sample. Ninety-five females and 79 males completed the Oxford–Liverpool Inventory of Feelings and Experiences (O-LIFE), which measures four separable aspects of schizotypy: cognitive disorganization, unusual experiences, introvertive anhedonia, and impulsive non-conformity. Subsequently, participants were administered a neurocognitive battery incorporating measures of executive skills including inhibition, cognitive flexibility, reasoning, and problem solving along with measures of attention and processing speed and both verbal and spatial working memory. In line with predictions, the current study found that higher scores on the subscales of unusual experiences, cognitive disorganization, and impulsive non-conformity related to worse performance on a measure of inhibition. Additionally, as introvertive anhedonia increased, both attention and processing speed and reasoning and problem-solving performance became more impaired. In conclusion, this study extends schizotypy literature by examining the subscales of the O-LIFE, and enables inferences to be drawn in relation to cognitive impairment in schizophrenia. PMID:26082726

  4. Higher glycemic load diet is associated with poorer nutrient intake in women with gestational diabetes mellitus.

    PubMed

    Louie, Jimmy Chun Yu; Markovic, Tania P; Ross, Glynis P; Foote, Deborah; Brand-Miller, Jennie C

    2013-04-01

    Changes in the quality and quantity of carbohydrate foods may compromise nutrient intake in women with gestational diabetes mellitus (GDM). We hypothesized that glycemic index, glycemic load (GL), carbohydrate intake, grains, and cereal product consumption would be associated with nutrient adequacy. Eighty-two women with GDM (61% of Asian background, 34% whites) completed a 3-day food record following their routine group nutrition education session. Nutrient intakes were compared to Nutrient Reference Values (NRV) for Australia and New Zealand. Nutrient intake across energy-adjusted tertiles of glycemic index, GL, carbohydrate intake, and intake of grains and cereal products were assessed. The majority of women (66%-99%) did not meet the NRV for fiber, folate, vitamin D, iodine, and iron, and exceeded NRV for saturated fat and sodium. Higher dietary GL was associated with lower intakes of total, monounsaturated, and polyunsaturated fat; vitamin E; and potassium (all P < .001). Higher grain intake was not significantly associated with intake of any micronutrients. In Australian women with GDM, high dietary GL predicts greater risk of poor nutrition.

  5. Is quality of life poorer for older adults with HIV/AIDS? International evidence using the WHOQOL-HIV.

    PubMed

    Skevington, S M

    2012-01-01

    Increasingly older adults are being diagnosed with HIV/AIDS. In 2002, UNAIDS indicated that 13 aspects of quality of life (QoL) were poorer for older adults, but only sparse, inconsistent cross-cultural evidence is available. This statement was investigated using a reliable, valid measure (the WHOQOL-HIV) distributed in nine cultures (eight countries). HIV positive and well adults (n = 2089) were assessed across 30 QoL facets; 403 were 40+ years. It was confirmed that sleep, fatigue and sex-life were poorer areas of QoL for older HIV adults than younger. Furthermore, they could be misinterpreted as normal ageing signs. Moreover, older people reported greater dependency on medication. However, older HIV adults had better QoL than expected on 11 dimensions; negative feelings, social inclusion, and several environmental and spiritual facets. This highlights the extent of poor QoL in younger adults. After accounting for culture and gender, overall QoL and health in older HIV adults was explained by eight facets comprising 61.3% of the variance. Social relationships were paramount, especially personal relationships (41%), but support and sex-life also. Energy, negative feelings, cognitions, financial resources and HIV symptoms also contributed. Social interventions for ageing communities would improve well-being. This evidence could support global ageing and HIV policy.

  6. Predicting the maximum-tolerated dose of PNU-159548 (4-demethoxy-3'-deamino-3'-aziridinyl-4'-methylsulphonyl-daunorubicin) in humans using CFU-GM clonogenic assays and prospective validation.

    PubMed

    Moneta, D; Geroni, C; Valota, O; Grossi, P; de Jonge, M J A; Brughera, M; Colajori, E; Ghielmini, M; Sessa, C

    2003-03-01

    A haematotoxicity model was proposed by Parchment in 1998 to predict the maximum-tolerated dose (MTD) in humans of myelosuppressive antitumour agents by combining data from in vitro clonogenic assays on haematopoietic progenitors and in vivo systemic exposure data in animals. A prospective validation of this model in humans was performed with PNU-159548, a novel agent showing selective dose-limiting myelosuppression in animals. PNU-159548 and its main metabolite, PNU-169884, were tested in vitro on murine, canine and human colony forming units-granulocyte macrophages (CFU-GM) and in vivo on mice and dogs. The IC(90x) ratios (IC(x)=concentration inhibiting x% of colony growth) for CFU-GM and drug plasma protein binding were used to adjust the target plasma concentrations versus time curve (AUC) and predict the human MTD. The predicted MTD was compared with values achieved in phase I studies. Canine CFU-GM were 6-fold more sensitive (P<0.01) and murine CFU-GM 1.7-fold less sensitive (P<0.05) to PNU-159548 treatment than the human progenitors. PNU-169884 behaved similarly to PNU-159548. The predicted MTDs in humans calculated from data in mice and dogs were 15 and 38 mg/m(2), respectively. Overall, 61 patients were treated in two phase I studies, at doses ranging from 1.0 to 16 mg/m(2). Thrombocytopenia was dose-limiting with a MTD of 14 and 16 mg/m(2) in heavily and minimally pretreated/non-pretreated patients, respectively. Adjusting animal MTD data by means of the CFU-GM ratio between species can predict the human MTD with a good quantitative accuracy. Inhibition of common haemopoietic progenitors by PNU-159548 induced neutropenia/thrombocytopenia in animals and thrombocytopenia in patients, probably due to the higher sensitivity to the compound observed in human colony forming units-megakaryocyte (CFU-MK).

  7. What Explains Divorced Women’s Poorer Health?: The Mediating Role of Health Insurance and Access to Health Care in a Rural Iowan Sample*

    PubMed Central

    Lavelle, Bridget; Lorenz, Frederick O.; Wickrama, K. A. S.

    2012-01-01

    The economic restructuring in rural areas in recent decades has been accompanied by rising marital instability. To examine the implications of the increase in divorce for the health of rural women, we examine how marital status predicts adequacy of health insurance coverage and health care access, and whether these factors help to account for the documented association between divorce and later illness. Analyzing longitudinal data from a cohort of over 400 married and recently divorced rural Iowan women, we decompose the total effect of divorce on physical illness a decade later using structural equation modeling. Divorced women are less likely to report adequate health insurance in the years following divorce, inhibiting their access to medical care and threatening their physical health. Full-time employment acts as a buffer against insurance loss for divorced women. The growth of marital instability in rural areas has had significant ramifications for women’s health; the decline of adequate health insurance coverage following divorce explains a component of the association between divorced status and poorer long-term health outcomes. PMID:23457418

  8. Incidence of malignant thyroid tumors in humans after exposure to diagnostic doses of /sup 131/I. II. Estimation of thyroid gland size, thyroid radiation dose, and predicted versus observed number of malignant thyroid tumors

    SciTech Connect

    Holm, L.E.; Eklund, G.; Lundell, G.

    1980-12-01

    The size of the thyroid glands was analyzed for 10% of the patients in a selected group that had been exposed to diagnostic doses of /sup 131/I. The mean thyroid gland weight +- SD was 50 +- 33 g for patients 20 or more years of age and 10 +- 5 g for patients less than 20 years of age. With the present follow-up, diagnostic doses of /sup 131/I appeared not to be associated with an increased risk for later development of malignant thyroid tumors. Possible reasons for the difference between the observed number of such tumors and the number expected (47 to 124) on the basis of risk estimates of the United Nations Scientific Committee on the Effects of Atomic Radiation are discussed.

  9. Predicting Grade 3 Acute Diarrhea During Radiation Therapy for Rectal Cancer Using a Cutoff-Dose Logistic Regression Normal Tissue Complication Probability Model

    SciTech Connect

    Robertson, John M.; Soehn, Matthias; Yan Di

    2010-05-01

    Purpose: Understanding the dose-volume relationship of small bowel irradiation and severe acute diarrhea may help reduce the incidence of this side effect during adjuvant treatment for rectal cancer. Methods and Materials: Consecutive patients treated curatively for rectal cancer were reviewed, and the maximum grade of acute diarrhea was determined. The small bowel was outlined on the treatment planning CT scan, and a dose-volume histogram was calculated for the initial pelvic treatment (45 Gy). Logistic regression models were fitted for varying cutoff-dose levels from 5 to 45 Gy in 5-Gy increments. The model with the highest LogLikelihood was used to develop a cutoff-dose normal tissue complication probability (NTCP) model. Results: There were a total of 152 patients (48% preoperative, 47% postoperative, 5% other), predominantly treated prone (95%) with a three-field technique (94%) and a protracted venous infusion of 5-fluorouracil (78%). Acute Grade 3 diarrhea occurred in 21%. The largest LogLikelihood was found for the cutoff-dose logistic regression model with 15 Gy as the cutoff-dose, although the models for 20 Gy and 25 Gy had similar significance. According to this model, highly significant correlations (p <0.001) between small bowel volumes receiving at least 15 Gy and toxicity exist in the considered patient population. Similar findings applied to both the preoperatively (p = 0.001) and postoperatively irradiated groups (p = 0.001). Conclusion: The incidence of Grade 3 diarrhea was significantly correlated with the volume of small bowel receiving at least 15 Gy using a cutoff-dose NTCP model.

  10. INCREASED INTERNET USE AND POORER ABILITY TO MANAGE EMOTIONS IN YOUTH AT HIGH-RISK FOR PSYCHOSIS

    PubMed Central

    Pelletier-Baldelli, Andrea; Ives, Lindsay; Mittal, Vijay A.

    2015-01-01

    The relationship between Internet use and social behavior remains unknown. However, research indicates that Internet use (IU) may have some causal role in certain types of psychopathology and overall functioning. In contrast, other work suggests that IU may be protective and buffer against social isolation. Poorer emotional processing (EP) is characteristic of schizophrenia, and these deficits are present prior to illness onset (the ultra high-risk period (UHR)). UHR adolescents/young adults also fall within an age demographic characterized by extensive IU, which suggests that evaluating a link between IU and social behavior in this population may be especially informative. The present study examined the relationship between IU and emotional processing in 98 adolescents/young adults (52 UHR youth and 46 controls). UHR youth exhibited greater problematic IU (β = −6.49, F(1,95) = 8.79, p = 0.002) and social withdrawal/problems resulting from this use (β = −3.23, F(1,95) = 11.43, p < 0.001), as well deficits in emotional processing in comparison to healthy peers (β = 4.59, F(1,94) = 5.52, p = 0.011). Furthermore, the social problems resulting from IU was significantly related to the ability to process emotional information in the UHR group (β = −0.51, t(1,48) = −2.10, p = 0.021). UHR youth showed evidence of problematic IU relative to controls, and the social problems resulting from IU related to poorer EP. Findings replicate extant research involving other psychosis risk populations, while adding information regarding how social processes may relate to IU. PMID:26855886

  11. Regret on Choice of Colorectal Cancer Screening Modality Was Associated with Poorer Screening Compliance: A 4-Year Prospective Cohort Study

    PubMed Central

    Wong, Martin C. S.; Ching, Jessica Y. L.; Chan, Victor C. W.; Bruggemann, Renee; Lam, Thomas Y. T.; Luk, Arthur K. C.; Wu, Justin C. Y.; Chan, Francis K. L.; Sung, Joseph J. Y.

    2015-01-01

    Purpose Very few studies examined the issue of regret on choosing colorectal cancer (CRC) screening tests. We evaluated the determinants of regret and tested the hypothesis that regret over screening choices was associated with poorer screening compliance. Methods A bowel cancer screening centre invited all Hong Kong citizens aged 50-70 years who were asymptomatic of CRC to participate in free-of-charge screening programmes. Upon attendance they attended health seminars on CRC and its screening, and were offered an option to choose yearly faecal immunochemical test (FIT) for up to four years vs. one direct colonoscopy. They were not allowed to switch the screening option after decision. A self-administered, four-item validated survey was used to assess whether they regretted over their choice (> 2 = regretful from a scale of 0 [no regret]-5 [extreme regret]). A binary logistic regression model evaluated if initial regret over their choice was associated with poorer programme compliance. Results From 4,341 screening participants who have chosen FIT or colonoscopy, 120 (2.8%) regretted over their decision and 1,029 (23.7%) were non-compliant with the screening programme. Younger subjects and people who felt pressure when making their decision were associated with regret. People who regretted their decision were 2.189 (95% C.I. 1.361-3.521, p = 0.001) times more likely to be non-compliant with the programme. Conclusions This study is the first to show that regret over the initial CRC screening choice was associated with later non-compliance. Screening participants who expressed regret over their choice should receive additional reminders to improve their programmatic compliance. PMID:25875160

  12. Comparison of MCNPX and GEANT4 to Predict the Contribution of Non-elastic Nuclear Interactions to Absorbed Dose in Water, PMMA and A150

    NASA Astrophysics Data System (ADS)

    Shtejer, K.; Arruda-Neto, J. D. T.; Schulte, R.; Wroe, A.; Rodrigues, T. E.; de Menezes, M. O.; Moralles, M.; Guzmán, F.; Manso, M. V.

    2008-08-01

    Proton induced non-elastic nuclear reactions play an important role in the dose distribution of clinically used proton beams as they deposit dose of high biological effectiveness both within the primary beam path as well as outside the beam to untargeted tissues. Non-elastic nuclear reactions can be evaluated using transport codes based on the Monte Carlo method. In this work, we have utilized the Los Alamos code MCNPX and the CERN GEANT4 toolkit, which are currently the most widely used Monte Carlo programs for proton radiation transport simulations in medical physics, to study the contribution of non-elastic nuclear interactions to the absorbed dose of proton beams in the therapeutic energy range. The impact of different available theoretical models to address the nuclear reaction process was investigated. The contribution of secondary particles from non-elastic nuclear reactions was calculated in three materials relevant in radiotherapy applications: water, PMMA and A150. The results evidence that there are differences in the calculated contribution of the secondary particles heavier than protons to the absorbed dose, with different approaches to model the nuclear reactions. The MCNPX calculation give rise to a larger contribution of d, t, α3He to the total dose compared to the GEANT4 physical models chosen in this work.

  13. Comparison of MCNPX and GEANT4 to Predict the Contribution of Non-elastic Nuclear Interactions to Absorbed Dose in Water, PMMA and A150

    SciTech Connect

    Shtejer, K.; Arruda-Neto, J. D. T.; Rodrigues, T. E.; Schulte, R.; Wroe, A.; Menezes, M. O. de; Moralles, M.

    2008-08-11

    Proton induced non-elastic nuclear reactions play an important role in the dose distribution of clinically used proton beams as they deposit dose of high biological effectiveness both within the primary beam path as well as outside the beam to untargeted tissues. Non-elastic nuclear reactions can be evaluated using transport codes based on the Monte Carlo method. In this work, we have utilized the Los Alamos code MCNPX and the CERN GEANT4 toolkit, which are currently the most widely used Monte Carlo programs for proton radiation transport simulations in medical physics, to study the contribution of non-elastic nuclear interactions to the absorbed dose of proton beams in the therapeutic energy range. The impact of different available theoretical models to address the nuclear reaction process was investigated. The contribution of secondary particles from non-elastic nuclear reactions was calculated in three materials relevant in radiotherapy applications: water, PMMA and A150. The results evidence that there are differences in the calculated contribution of the secondary particles heavier than protons to the absorbed dose, with different approaches to model the nuclear reactions. The MCNPX calculation give rise to a larger contribution of d, t, {alpha}{sup 3}He to the total dose compared to the GEANT4 physical models chosen in this work.

  14. A study of predicted bone marrow distribution on calculated marrow dose from external radiation exposures using two sets of image data for the same individual.

    PubMed

    Caracappa, Peter F; Chao, T C Ephraim; Xu, X George

    2009-06-01

    Red bone marrow is among the tissues of the human body that are most sensitive to ionizing radiation, but red bone marrow cannot be distinguished from yellow bone marrow by normal radiographic means. When using a computational model of the body constructed from computed tomography (CT) images for radiation dose, assumptions must be applied to calculate the dose to the red bone marrow. This paper presents an analysis of two methods of calculating red bone marrow distribution: 1) a homogeneous mixture of red and yellow bone marrow throughout the skeleton, and 2) International Commission on Radiological Protection cellularity factors applied to each bone segment. A computational dose model was constructed from the CT image set of the Visible Human Project and compared to the VIP-Man model, which was derived from color photographs of the same individual. These two data sets for the same individual provide the unique opportunity to compare the methods applied to the CT-based model against the observed distribution of red bone marrow for that individual. The mass of red bone marrow in each bone segment was calculated using both methods. The effect of the different red bone marrow distributions was analyzed by calculating the red bone marrow dose using the EGS4 Monte Carlo code for parallel beams of monoenergetic photons over an energy range of 30 keV to 6 MeV, cylindrical (simplified CT) sources centered about the head and abdomen over an energy range of 30 keV to 1 MeV, and a whole-body electron irradiation treatment protocol for 3.9 MeV electrons. Applying the method with cellularity factors improves the average difference in the estimation of mass in each bone segment as compared to the mass in VIP-Man by 45% over the homogenous mixture method. Red bone marrow doses calculated by the two methods are similar for parallel photon beams at high energy (above about 200 keV), but differ by as much as 40% at lower energies. The calculated red bone marrow doses differ

  15. Effectiveness of low-dose pasireotide in a patient with Cushing’s disease: antiproliferative effect and predictivity of a short pasireotide suppression test

    PubMed Central

    Grossrubatscher, Erika; Zampetti, Benedetta; Dalino Ciaramella, Paolo; Doneda, Paola; Loli, Paola

    2015-01-01

    Key Clinical Message This case shows efficacy of low-dose pasireotide in biochemical and clinical control of severe hypercortisolism and in tumor volume reduction in a patient with an ACTH-secreting macroadenoma. The drug may be an option for long-term treatment in some patients where control of tumor mass is an important clinical endpoint. PMID:26331021

  16. Effectiveness of low-dose pasireotide in a patient with Cushing's disease: antiproliferative effect and predictivity of a short pasireotide suppression test.

    PubMed

    Grossrubatscher, Erika; Zampetti, Benedetta; Dalino Ciaramella, Paolo; Doneda, Paola; Loli, Paola

    2015-08-01

    This case shows efficacy of low-dose pasireotide in biochemical and clinical control of severe hypercortisolism and in tumor volume reduction in a patient with an ACTH-secreting macroadenoma. The drug may be an option for long-term treatment in some patients where control of tumor mass is an important clinical endpoint.

  17. Poorer frontolimbic white matter integrity is associated with chronic cannabis use, FAAH genotype, and increased depressive and apathy symptoms in adolescents and young adults

    PubMed Central

    Shollenbarger, Skyler G.; Price, Jenessa; Wieser, Jon; Lisdahl, Krista

    2015-01-01

    Background The heaviest period of cannabis use coincides with ongoing white matter (WM) maturation. Further, cannabis-related changes may be moderated by FAAH genotype (rs324420). We examined the association between cannabis use and FAAH genotype on frontolimbic WM integrity in adolescents and emerging adults. We then tested whether observed WM abnormalities were linked with depressive or apathy symptoms. Methods Participants included 37 cannabis users and 37 healthy controls (33 female; ages 18–25). Multiple regressions examined the independent and interactive effects of variables on WM integrity. Results Regular cannabis users demonstrated reduced WM integrity in the bilateral uncinate fasciculus (UNC) (MD, right: p = .009 and left: p = .009; FA, right: p = .04 and left: p = .03) and forceps minor (fMinor) (MD, p = .03) compared to healthy controls. Marginally reduced WM integrity in the cannabis users was found in the left anterior thalamic radiation (ATR) (FA, p = .08). Cannabis group ∗ FAAH genotype interaction predicted WM integrity in bilateral ATR (FA, right: p = .05 and left: p = .001) and fMinor (FA, p = .02). In cannabis users, poorer WM integrity was correlated with increased symptoms of depression and apathy in bilateral ATR and UNC. Conclusions Consistent with prior findings, cannabis use was associated with reduced frontolimbic WM integrity. WM integrity was also moderated by FAAH genotype, in that cannabis-using FAAH C/C carriers and A carrying controls had reduced WM integrity compared to control C/C carriers. Observed frontolimbic white matter abnormalities were linked with increased depressive and apathy symptoms in the cannabis users. PMID:26106535

  18. Threshold doses and prediction of visually apparent liver dysfunction after stereotactic body radiation therapy in cirrhotic and normal livers using magnetic resonance imaging

    PubMed Central

    Doi, Hiroshi; Shiomi, Hiroya; Masai, Norihisa; Tatsumi, Daisaku; Igura, Takumi; Imai, Yasuharu; Oh, Ryoong-Jin

    2016-01-01

    The purpose of the present study was to investigate the threshold dose for focal liver damage after stereotactic body radiation therapy (SBRT) in cirrhotic and normal livers using magnetic resonance imaging (MRI). A total of 64 patients who underwent SBRT for liver tumors, including 54 cirrhotic patients with hepatocellular carcinoma (HCC) and 10 non-cirrhotic patients with liver metastases, were analyzed. MRI was performed 3−6 months after SBRT, using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced T1-weighted sequences. All MRI datasets were merged with 3D dosimetry data. All dose distributions were corrected to the biologically effective dose using the linear–quadratic model with an assumed α/β ratio of 2 Gy. The development of liver dysfunction was validly correlated with isodose distribution. The median biologically effective dose (BED2) that provoked liver dysfunction was 57.3 (30.0−227.9) and 114.0 (70.4−244.9) Gy in cirrhotic and normal livers, respectively (P = 0.0002). The BED2 associated with a >5% risk of liver dysfunction was 38.5 in cirrhotic livers and 70.4 Gy in normal livers. The threshold BED2 for liver dysfunction was not significantly different between Child−Pugh A and B patients (P = 0.0719). Moreover, the fractionation schedule was not significantly correlated with threshold BED2 for liver dysfunction in the cirrhotic liver (P = 0.1019). In the cirrhotic liver, fractionation regimen and Child−Pugh classification did not significantly influence the threshold BED2 for focal liver damage after SBRT. We suggest that the threshold BED2 for liver dysfunction after SBRT is 40 and 70 Gy in the cirrhotic and normal liver, respectively. PMID:26983986

  19. Assessment of the accuracy of an MCNPX-based Monte Carlo simulation model for predicting three-dimensional absorbed dose distributions.

    PubMed

    Titt, U; Sahoo, N; Ding, X; Zheng, Y; Newhauser, W D; Zhu, X R; Polf, J C; Gillin, M T; Mohan, R

    2008-08-21

    In recent years, the Monte Carlo method has been used in a large number of research studies in radiation therapy. For applications such as treatment planning, it is essential to validate the dosimetric accuracy of the Monte Carlo simulations in heterogeneous media. The AAPM Report no 105 addresses issues concerning clinical implementation of Monte Carlo based treatment planning for photon and electron beams, however for proton-therapy planning, such guidance is not yet available. Here we present the results of our validation of the Monte Carlo model of the double scattering system used at our Proton Therapy Center in Houston. In this study, we compared Monte Carlo simulated depth doses and lateral profiles to measured data for a magnitude of beam parameters. We varied simulated proton energies and widths of the spread-out Bragg peaks, and compared them to measurements obtained during the commissioning phase of the Proton Therapy Center in Houston. Of 191 simulated data sets, 189 agreed with measured data sets to within 3% of the maximum dose difference and within 3 mm of the maximum range or penumbra size difference. The two simulated data sets that did not agree with the measured data sets were in the distal falloff of the measured dose distribution, where large dose gradients potentially produce large differences on the basis of minute changes in the beam steering. Hence, the Monte Carlo models of medium- and large-size double scattering proton-therapy nozzles were valid for proton beams in the 100 MeV-250 MeV interval.

  20. A randomized controlled trial investigating the use of a predictive nomogram for the selection of the FSH starting dose in IVF/ICSI cycles.

    PubMed

    Allegra, Adolfo; Marino, Angelo; Volpes, Aldo; Coffaro, Francesco; Scaglione, Piero; Gullo, Salvatore; La Marca, Antonio

    2017-01-23

    The number of oocytes retrieved is a relevant intermediate outcome in women undergoing IVF/intracytoplasmic sperm injection (ICSI). This trial compared the efficiency of the selection of the FSH starting dose according to a nomogram based on multiple biomarkers (age, day 3 FSH, anti-Müllerian hormone) versus an age-based strategy. The primary outcome measure was the proportion of women with an optimal number of retrieved oocytes defined as 8-14. At their first IVF/ICSI cycle, 191 patients underwent a long gonadotrophin-releasing hormone agonist protocol and were randomized to receive a starting dose of recombinant (human) FSH, based on their age (150 IU if ≤35 years, 225 IU if >35 years) or based on the nomogram. Optimal response was observed in 58/92 patients (63%) in the nomogram group and in 42/99 (42%) in the control group (+21%, 95% CI = 0.07 to 0.35, P = 0.0037). No significant differences were found in the clinical pregnancy rate or the number of embryos cryopreserved per patient. The study showed that the FSH starting dose selected according to ovarian reserve is associated with an increase in the proportion of patients with an optimal response: large trials are recommended to investigate any possible effect on the live-birth rate.

  1. Predicting the "First dose in children" of CYP3A-metabolized drugs: Evaluation of scaling approaches and insights into the CYP3A7-CYP3A4 switch at young ages.

    PubMed

    Strougo, Ashley; Yassen, Ashraf; Monnereau, Claire; Danhof, Meindert; Freijer, Jan

    2014-09-01

    First-dose-in-children relies on the prediction of clearance from adults for which little information is available on the accuracy of the scaling-approaches applied. For CYP3A-metabolized compounds, scaling of clearance is further challenged by different isoforms and by the CYP3A7 to CYP3A4 switch at young ages. This investigation aimed to evaluate the accuracy of two frequently used scaling approaches and to gain insights into the ontogeny of CYP3A. Hence, a literature database was compiled containing 203 clearance values from term-neonates to adults for 18 CYP3A-metabolized compounds. The clearances in adults were scaled to children using (i) allometric scaling plus maturation function and (ii) a mechanistic approach based on the well-stirred model. Three maturation functions were separately evaluated. In children >3 months, all approaches were interchangeable heeding the maturation function applied and biases were mostly observed in children <3 months. The results from a sensitivity analysis indicate that these biases are possibly caused by disregarding the CYP3A7 activity which could account for up to 86% of the metabolism in term-neonates. Only the mechanistic approach using an overall-CYP3A maturation function led to unbiased predictions of clearances across all ages. The current investigation adds to the predictions of the first-dose-in-children of compounds (partially) metabolized by CYP3A.

  2. Poorer elbow proprioception in patients with lateral epicondylitis than in healthy controls: a cross-sectional study.

    PubMed

    Juul-Kristensen, Birgit; Lund, Hans; Hansen, Klaus; Christensen, Hanne; Danneskiold-Samsøe, Bente; Bliddal, Henning

    2008-01-01

    Two groups of women, 15 patients with lateral epicondylitis and 21 healthy controls, were studied to compare proprioception in the elbows and knees between the groups. Outcome measures were absolute error and variable error for joint position sense and for threshold to detection of a passive movement. Both absolute error and variable error of threshold to detection of a passive movement were greater in the lateral epicondylitis-diagnosed elbows than in the controls' elbows (lateral epicondylitis, 1.8 degrees vs controls 1.1 degrees, P = .026; lateral epicondylitis, 0.8 degrees vs controls 0.3 degrees, P = .015), and there was a tendency toward a greater absolute error of joint position sense compared with the control elbows (lateral epicondylitis, 8.2 degrees vs controls, 5.6 degrees; P = .078). Absolute error of joint position sense was greater in the elbows than in the knees of the lateral epicondylitis patients, but no group differences were found for knees. Proprioception seems, therefore, to be poorer in elbows with lateral epicondylitis elbows than in the controls' elbows. This needs to be taken into consideration in the management of lateral epicondylitis.

  3. Social Comparisons are Associated with Poorer and Riskier Financial Decision Making, no Matter whether Encounters are Sporadic or Repeated.

    PubMed

    Barrós-Loscertales, Alfonso; Espín, Antonio M; Perales, José C

    2016-09-20

    Previous research suggests that social comparisons affect decision making under uncertainty. However, the role of the length of the social interaction for this relationship remains unknown. This experiment tests the effect of social comparisons on financial risk taking and how this effect is modulated by whether social encounters are sporadic or repeated. Participants carried out a computer task consisting of a series of binary choices between lotteries of varying profitability and risk, with real monetary stakes. After each decision, participants could compare their own payoff to that of a counterpart who made the same decision at the same time and whose choices/earnings did not affect the participants' earnings. The design comprised three between-subjects treatments which differed in the nature of the social interaction: participants were informed that they would be matched with either (a) a different participant in each trial, (b) the same participant across all trials, or (c) a "virtual participant", i.e., a computer algorithm. Compared to the non-social condition (c), subjects in both social conditions (a and b) chose lotteries with lower expected value (z = -3.10, p < .01) and higher outcome variance (z = 2.13, p = .03). However, no differences were found between the two social conditions (z = 1.15, p = .25 and z = 0.35, p = .73, respectively). These results indicate that social comparison information per se leads to poorer and riskier financial decisions, irrespective of whether or not the referent other is encountered repeatedly.

  4. Preclinical pharmacokinetics of MHAA4549A, a human monoclonal antibody to influenza A virus, and the prediction of its efficacious clinical dose for the treatment of patients hospitalized with influenza A

    PubMed Central

    Gupta, Priyanka; Kamath, Amrita V.; Park, Summer; Chiu, Henry; Lutman, Jeff; Maia, Mauricio; Tan, Man-Wah; Xu, Min; Swem, Lee; Deng, Rong

    2016-01-01

    ABSTRACT MHAA4549A is a human immunoglobulin G1 (IgG1) monoclonal antibody that binds to a highly conserved epitope on the stalk of influenza A hemagglutinin and blocks the hemagglutinin-mediated membrane fusion in the endosome, neutralizing all known human influenza A strains. Pharmacokinetics (PK) of MHAA4549A and its related antibodies were determined in DBA/2J and Balb-c mice at 5 mg/kg and in cynomolgus monkeys at 5 and 100 mg/kg as a single intravenous dose. Serum samples were analyzed for antibody concentrations using an ELISA and the PK was evaluated using WinNonlin software. Human PK profiles were projected based on the PK in monkeys using species-invariant time method. The human efficacious dose projection was based on in vivo nonclinical pharmacological active doses, exposure in mouse infection models and expected human PK. The PK profiles of MHAA4549A and its related antibody showed a linear bi-exponential disposition in mice and cynomolgus monkeys. In mice, clearance and half-life ranged from 5.77 to 9.98 mL/day/kg and 10.2 to 5.76 days, respectively. In cynomolgus monkeys, clearance and half-life ranged from 4.33 to 4.34 mL/day/kg and 11.3 to 11.9 days, respectively. The predicted clearance in humans was ∼2.60 mL/day/kg. A single intravenous dose ranging from 15 to 45 mg/kg was predicted to achieve efficacious exposure in humans. In conclusion, the PK of MHAA4549A was as expected for a human IgG1 monoclonal antibody that lacks known endogenous host targets. The predicted clearance and projected efficacious doses in humans for MHAA4549A have been verified in a Phase 1 study and Phase 2a study, respectively. PMID:27031797

  5. The significance of antral follicle size prior to stimulation in predicting ovarian response in a multiple dose GnRH antagonist protocol.

    PubMed

    Lai, Qiaohong; Chen, Cai; Zhang, Zhijun; Zhang, Shu; Yu, Qilin; Yang, Ping; Hu, Jun; Wang, Cong-Yi

    2013-01-01

    Prediction of ovarian responses prior to stimulation is not only useful for patient counseling, but also important in tailoring the optimal dosage of gonadotrophin for individual patients. By prospectively study of 214 women undergoing in vitro fertilization and embryo transfer (IVF-ET) treatment, we obtained data supporting that antral follicle size could be an additional valuable predictive marker other than the antral follicle count (AFC) in predicting ovarian response. Our studies revealed that AFC achieved the best predictive value in relation to the number of oocyte obtained, followed by antral follicle size, basal follicle stimulating hormone (FSH) and body mass index (BMI). Unlike AFC, antral follicle size was noted to be negatively correlated with the dosage (R = -0.493) and duration (R = -0.465) of rFSH stimulation. Antral follicle size was also found with higher negative regression coefficient (B = -0.661) as compared with that of basal FSH concentration (B = -0.326) and BMI (b = -0.281). More importantly, women with antral follicle size 6-7 mm showed significantly higher AFC, oocytes retrieved, fertilized oocytes and grade I/II embryos along with much lower transfer cycle cancellation rate (7.5% vs. 16-17%). Together, our data suggest that basal antral follicle size could be a valued predictive marker in women with IVF-ET treatment, in which women with antral follicle size 6-7 mm are likely predisposed to better IVF-ET outcomes.

  6. Factors predictive of early death in patients receiving high-dose CHOP (ACVB regimen) for aggressive non-Hodgkin's lymphoma: a GELA study.

    PubMed

    Dumontet, Charles; Mounier, Nicolas; Munck, Jean Nicolas; Bosly, André; Morschauser, Frank; Simon, Daniele; Marit, Gérald; Casasnovas, Olivier; Reman, Oumédaly; Molina, Thierry; Reyes, Felix; Coiffier, Bertrand

    2002-07-01

    Death during the induction phase of chemotherapy remains a common event in patients with aggressive non-Hodgkin's lymphoma (NHL). In a series of patients with aggressive NHL homogeneously treated with intensive induction chemotherapy [ACVB (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) regimen], we determined the clinical and biological parameters that were predictive of early death. Early death was defined as death, for whatever reason, occurring within 100 d of randomization. Predictive factors were identified by logistic regression and an index predictive for individual risk of early death was designed. Among the 2210 patients treated with ACVB, there were 162 (7.3%) early deaths. There was no significant reduction in the rate of early death between 1987 and 1998. In a multivariate analysis, age > 60 years, Eastern Cooperative Oncology Group performance status > 1, serum lactate dehydrogenase > normal, serum albumin < 30 g/l, leucocyte counts > 10 x 10(9)/l and haemoglobin levels < 8.5 g/dl were found to be independent predictive factors for early death. An early death index was designed, enabling the evaluation of the individual risk of early death in young (range 2-31% risk of early death) and elderly patients (range 5-53%). Clinical and biological parameters available at diagnosis can help physicians identify patients with aggressive lymphoma at low or high risk of early death.

  7. Microvascular diabetic complications are more prevalent in India compared to Mauritius and the UK due to poorer diabetic control.

    PubMed

    Potluri, Rahul; Purmah, Yanish; Dowlut, Mohammad; Sewpaul, Nilesh; Lavu, Deepthi

    2009-11-01

    Type 2 diabetes mellitus (T2DM) is a growing worldwide problem with WHO estimates suggesting that 300 million people will be affected by 2025. T2DM could result in both microvascular and macrovascular complications but the presentation of these complications could vary globally and be influenced by diabetic control. We investigated the prevalence of these complications by surveying 787 patients of south-Asian origin in diabetic clinics in the UK (n=351), Mauritius (n=173) and India (n=263). We found the prevalence of microvascular complications such as retinopathy (India 16.3%; Mauritius 2.3%; UK 2.6%), nephropathy (India 20.5%; Mauritius 10.5%; UK 2.3%) and neuropathy (India 8.4%; Mauritius 1.2%; UK 5.1%) complications to be significantly higher in India compared to Mauritius and the UK (p<0.05). Interestingly, macrovascular complications such as cardiovascular disease were significantly more prevalent in Mauritius and the UK compared to India (p<0.05). The use of diabetic medication such as Metformin, Sulphonylureas and Insulin was significantly higher in the UK and Mauritius compared to India (p<0.05). The mean HbA1c was significantly higher in India compared to the UK (India 8.68%; UK 8.30%). Our results suggest that microvascular complications are higher in India due to poorer diabetic control. Our findings could be explained by late-onset presentation of diabetic patients in India due to the lack of primary care initiatives to screen and monitor treatment of T2DM. Furthermore, the poor diabetic control in India could reflect a dearth of clinical, evidence-based-knowledge regarding diabetic medication amongst Indian physicians. In view of the global increase in T2DM, this is a major concern for Indian healthcare.

  8. Urinary Metabolites of the Dietary Carcinogen PhIP are Predictive of Colon DNA Adducts After a Low Dose Exposure in Humans

    SciTech Connect

    Malfatti, M; Dingley, K; Nowell, S; Ubick, E; Mulakken, N; Nelson, D; Lang, N; Felton, J; Turteltaub, K

    2006-04-28

    Epidemiologic evidence indicates that exposure to heterocyclic amines (HAs) in the diet is an important risk factor for the development of colon cancer. Well-done cooked meats contain significant levels of HAs which have been shown to cause cancer in laboratory animals. To better understand the mechanisms of HA bioactivation in humans, the most mass abundant HA, 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), was used to assess the relationship between PhIP metabolism and DNA adduct formation. Ten human volunteers were administered a dietary relevant dose of [{sup 14}C]PhIP 48-72 h prior to surgery to remove colon tumors. Urine was collected for 24 h after dosing for metabolite analysis, and DNA was extracted from colon tissue and analyzed by accelerator mass spectrometry for DNA adducts. All ten subjects were phenotyped for CYP1A2, NAT2, and SULT1A1 enzyme activity. Twelve PhIP metabolites were detected in the urine samples. The most abundant metabolite in all volunteers was N-hydroxy-PhIP-N{sup 2}-glucuronide. Metabolite levels varied significantly between the volunteers. Interindividual differences in colon DNA adducts levels were observed between each individual. The data showed that individuals with a rapid CYP1A2 phenotype and high levels of urinary N-hydroxy-PhIP-N{sup 2}-glucuronide, had the lowest level of colon PhIP-DNA adducts. This suggests that glucuronidation plays a significant role in detoxifying N-hydroxy-PhIP. The levels of urinary N-hydroxy-PhIP-N{sup 2}-glucuronide were negatively correlated to colon DNA adduct levels. Although it is difficult to make definite conclusions from a small data set, the results from this pilot study have encouraged further investigations using a much larger study group.

  9. The Percent of Positive Biopsy Cores Improves Prediction of Prostate Cancer-Specific Death in Patients Treated With Dose-Escalated Radiotherapy

    SciTech Connect

    Qian Yushen; Feng, Felix Y.; Halverson, Schuyler; Blas, Kevin; Sandler, Howard M.; Hamstra, Daniel A.

    2011-11-01

    Purpose: To examine the prognostic utility of the percentage of positive cores (PPC) at the time of prostate biopsy for patients treated with dose-escalated external beam radiation therapy. Methods and Materials: We performed a retrospective analysis of patients treated at University of Michigan Medical Center to at least 75 Gy. Patients were stratified according to PPC by quartile, and freedom from biochemical failure (nadir + 2 ng/mL), freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival (OS) were assessed by log-rank test. Receiver operator characteristic (ROC) curve analysis was used to determine the optimal cut point for PPC stratification. Finally, Cox proportional hazards multivariate regression was used to assess the impact of PPC on clinical outcome when adjusting for National Comprehensive Cancer Network (NCCN) risk group and androgen deprivation therapy. Results: PPC information was available for 651 patients. Increasing-risk features including T stage, prostate-specific antigen, Gleason score, and NCCN risk group were all directly correlated with increasing PPC. On log-rank evaluation, all clinical endpoints, except for OS, were associated with PPC by quartile, with worse clinical outcomes as PPC increased, with the greatest impact seen in the highest quartile (>66.7% of cores positive). ROC curve analysis confirmed that a cut point using two-thirds positive cores was most closely associated with CSS (p = 0.002; area under ROC curve, 0.71). On univariate analysis, stratifying patients according to PPC less than or equal to 66.7% vs. PPC greater than 66.7% was prognostic for freedom from biochemical failure (p = 0.0001), FFM (p = 0.0002), and CSS (p = 0.0003) and marginally prognostic for OS (p = 0.055). On multivariate analysis, after adjustment for NCCN risk group and androgen deprivation therapy use, PPC greater than 66.7% increased the risk for biochemical failure (p = 0.0001; hazard ratio [HR], 2.1 [95% confidence

  10. Oncogenic transformation of mesenchymal stem cells decreases Nrf2 expression favoring in vivo tumor growth and poorer survival

    PubMed Central

    2014-01-01

    Background The transcription factor Nrf2 is a key regulator of the cellular antioxidant response, and its activation by chemoprotective agents has been proposed as a potential strategy to prevent cancer. However, activating mutations in the Nrf2 pathway have been found to promote tumorigenesis in certain models. Therefore, the role of Nrf2 in cancer remains contentious. Methods We employed a well-characterized model of stepwise human mesenchymal stem cell (MSC) transformation and breast cancer cell lines to investigate oxidative stress and the role of Nrf2 during tumorigenesis. The Nrf2 pathway was studied by microarray analyses, qRT-PCR, and western-blotting. To assess the contribution of Nrf2 to transformation, we established tumor xenografts with transformed MSC expressing Nrf2 (n = 6 mice per group). Expression and survival data for Nrf2 in different cancers were obtained from GEO and TCGA databases. All statistical tests were two-sided. Results We found an accumulation of reactive oxygen species during MSC transformation that correlated with the transcriptional down-regulation of antioxidants and Nrf2-downstream genes. Nrf2 was repressed in transformed MSC and in breast cancer cells via oncogene-induced activation of the RAS/RAF/ERK pathway. Furthermore, restoration of Nrf2 function in transformed cells decreased reactive oxygen species and impaired in vivo tumor growth (P = 0.001) by mechanisms that included sensitization to apoptosis, and a decreased hypoxic/angiogenic response through HIF-1α destabilization and VEGFA repression. Microarray analyses showed down-regulation of Nrf2 in a panel of human tumors and, strikingly, low Nrf2 expression correlated with poorer survival in patients with melanoma (P = 0.0341), kidney (P = 0.0203) and prostate (P = 0.00279) cancers. Conclusions Our data indicate that oncogene-induced Nrf2 repression is an adaptive response for certain cancers to acquire a pro-oxidant state that favors cell survival and

  11. Locomotor activity in a novel environment predicts both responding for a visual stimulus and self-administration of a low dose of methamphetamine in rats

    PubMed Central

    Gancarz, Amy M.; San George, Michele A.; Ashrafioun, Lisham; Richards, Jerry B.

    2011-01-01

    There is evidence that visual stimuli used to signal drug delivery in self-administration procedures have primary reinforcing properties, and that drugs of abuse enhance the reinforcing properties of such stimuli. Here, we explored the relationships between locomotor activity, responding for a visual stimulus, and self-administration of methamphetamine (METH). Rats were classified as high or low responders based on activity levels in a novel locomotor chamber and were subsequently tested for responding to produce a visual stimulus followed by self-administration of a low dose of METH (0.025 mg/kg/infusion) paired with the visual stimulus. High responder rats responded more for the visual stimulus than low responder rats indicating that the visual stimulus was reinforcing and that operant responding for a visual stimulus has commonalities with locomotor activity in a novel environment. Similarly, high responder rats responded more for METH paired with a visual stimulus than low responder rats. Because of the reinforcing properties of the visual stimulus, it was not possible to determine if the rats were responding to produce the visual stimulus, METH or the combination. We speculate that responding to produce sensory reinforcers may be a measure of sensation seeking. These results indicate that visual stimuli have unconditioned reinforcing effects which may have a significant role in acquisition of drug self-administration, a role that is not yet well understood. PMID:21215305

  12. Autocrine TGF-β/ZEB/microRNA-200 signal transduction drives epithelial-mesenchymal transition: Kinetic models predict minimal drug dose to inhibit metastasis.

    PubMed

    Rateitschak, Katja; Kaderali, Lars; Wolkenhauer, Olaf; Jaster, Robert

    2016-08-01

    The epithelial-mesenchymal transition (EMT) is the crucial step that cancer cells must pass before they can undergo metastasis. The transition requires the activity of complex functional networks that downregulate properties of the epithelial phenotype and upregulate characteristics of the mesenchymal phenotype. The networks frequently include reciprocal repressions between transcription factors (TFs) driving the EMT and microRNAs (miRs) inducing the reverse process, termed mesenchymal-epithelial transition (MET). In this work we develop four kinetic models that are based on experimental data and hypotheses describing how autocrine transforming growth factor-β (TGF-β) signal transduction induces and maintains an EMT by upregulating the TFs ZEB1 and ZEB2 which repress the expression of the miR-200b/c family members. After successful model calibration we validate our models by predicting requirements for the maintenance of the mesenchymal steady state which agree with experimental data. Finally, we apply our validated kinetic models for the design of experiments in cancer therapy. We demonstrate how steady state properties of the kinetic models, combined with data from tumor-derived cell lines of individual patients, can predict the minimal amount of an inhibitor to induce a MET.

  13. Increased Tim-3 expression in peripheral NK cells predicts a poorer prognosis and Tim-3 blockade improves NK cell-mediated cytotoxicity in human lung adenocarcinoma.

    PubMed

    Xu, Liyun; Huang, Yanyan; Tan, Linlin; Yu, Wei; Chen, Dongdong; Lu, ChangChang; He, Jianying; Wu, Guoqing; Liu, Xiaoguang; Zhang, Yongkui

    2015-12-01

    T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) has been shown to play an important role in mediating NK-cell function in human diseases. However, the relationship between Tim-3 expression in natural killer (NK) cells and human lung adenocarcinoma remains unclear. We therefore investigated the expression of Tim-3 in NK cells and explored the effect of Tim-3 blockade on NK cell-mediated activity in human lung adenocarcinoma. Upregulated expression of Tim-3 on CD3-CD56+ cells (P<0.05) and CD3-CD56(dim) cells (P<0.05) of patients with lung adenocarcinoma was detected by flow cytometry. Moreover, Tim-3 expression in CD3-CD56+ NK cells was higher in patients with lung adenocarcinoma with lymph node metastasis (LNM) (P<0.05) or with tumor stage T3-T4 (P<0.05). Tim-3 expression in CD56(dim) NK-cell subset was higher in patients with tumor size ≥3cm (P<0.05), or LNM (P<0.05) or with tumor stage T3-T4 (P<0.05). Further analysis showed that higher expressions of Tim-3 on both CD3-CD56+ NK cells and CD56(dim) NK-cell subset were independently correlated with shorter overall survival of patients with lung adenocarcinoma (log-rank test, P=0.0418, 0.0406, respectively). Importantly, blockade of Tim-3 signaling with anti-Tim-3 antibodies resulted in the increased cytotoxicity and IFN-γ production of peripheral NK cells from patients with lung adenocarcinoma. Our data indicate that Tim-3 expression in NK cells can function as a prognostic biomarker in human lung adenocarcinoma and support that Tim-3 could be a new target for an immunotherapeutic strategy.

  14. THE USE OF PROTECTIVE BEHAVIORAL STRATEGIES IS RELATED TO REDUCED RISK IN HEAVY DRINKING COLLEGE STUDENTS WITH POORER MENTAL AND PHYSICAL HEALTH*

    PubMed Central

    Labrie, Joseph W.; Kenney, Shannon R.; Lac, Andrew

    2013-01-01

    The present study examined the moderating role of health status (physical, mental, and social health) and the relationships between protective behavioral strategies utilized to reduce high-risk drinking (e.g., avoiding drinking games, setting consumption limits, or having a designated driver) and alcohol use and negative consequences in a sample of heavy drinking college students (N = 1,820). In this high risk sample, multiple regression analyses showed that stronger social health was related to increased drinking, while poorer physical, mental, and social health were related to increased alcohol negative consequences. Further, moderation effects revealed that increasing the use of protective behaviors was associated with significantly less drinking in those with stronger social health, as well as significantly lower numbers of negative consequences among participants with poorer physical and mental health. Implications for college counselors and medical personnel are discussed. PMID:21381463

  15. Toward an understanding of decision making on complementary and alternative medicine use in poorer countries: the case of cancer care in Pakistan.

    PubMed

    Tovey, Philip; Chatwin, John; Ahmad, Salma

    2005-09-01

    During the past 2 decades, the study of complementary and alternative medicine (CAM) in general, and the sociological study of CAM in particular, have developed apace in richer countries. In addition to data on use levels and the nature of provision, there is now increasing research on issues such as motivation for use, decision-making processes, and so on. The integration of nonorthodox therapies into cancer care has been an important focus for such work. However, this interest has yet to be matched by work in poorer countries. While the nature of traditional medicine (TM) has long been of interest to anthropologists, the new context (marked by the globalized nature of CAMs existing alongside TM and allopathic treatment) has yet to be examined in any depth. In this article, the authors discuss the structural and cultural context of the first sociological research to be conducted into the role ofCAMandTMin cancer care in Pakistan. They identify some potentially important processes (ie, those identified in the limited existing literature and in anecdotal commentary), which are being tested by the new empirical study. The specific foci of the work are outlined. It is argued that research in poorer countries is essential both to ensure that an existing academic imbalance is addressed and to underpin more informed policy making in complex medically pluralistic (poorer) countries.

  16. A Phase II Study of Stereotactic Body Radiation Therapy for Low-Intermediate-High-Risk Prostate Cancer Using Helical Tomotherapy: Dose-Volumetric Parameters Predicting Early Toxicity

    PubMed Central

    Macias, Victor A.; Blanco, Manuel L.; Barrera, Inmaculada; Garcia, Rafael

    2014-01-01

    Endpoint: To assess early urinary (GU) and rectal (GI) toxicities after helical tomotherapy Stereotactic body radiation therapy (SBRT), and to determine their predictive factors. Methods: Since May 2012, 45 prostate cancer patients were treated with eight fractions of 5.48 (low risk, 29%) or 5.65 Gy (intermediate-high risk, 71%) on alternative days over 2.5 weeks. The exclusion criteria were Gleason score 9–10, PSA >40 ng/mL, cT3b-4, IPSS ≥20, and history of acute urinary retention. During the follow-up, a set of potential prognostic factors was correlated with urinary or rectal toxicity. Results: The median follow-up was 13.8 months (2–25 months). There were no grade ≥3 toxicities. Acute grade 2 GU complications were found in a 22.7% of men, but in 2.3% of patients at 1 month, 0% at 6 months, and 0% at 12 months. The correspondent figures for grade 2 GI toxicities were 20.4% (acute), 2.3% (1 month), 3.6% (6 months), and 5% (12 months). Acute GI toxicity was significantly correlated with the rectal volume (>15 cm3) receiving 28 Gy, only when expressed as absolute volume. The age (>72 years old) was a predictor of GI toxicity after 1 month of treatment. No correlation was found, however, between urinary toxicity and the other analyzed variables. IPSS increased significantly at the time of the last fraction and within the first month, returning to the baseline at sixth month. Urinary-related quality of life (IPSS question 8 score), it was not significantly worsen during radiotherapy returning to the baseline levels 1 month after the treatment. At 12 months follow-up patient’s perception of their urinary function improved significantly in comparison with the baseline. Conclusion: Our scheme of eight fractions on alternative days delivered using helical tomotherapy is well tolerated. We recommend using actual volume instead of percentual volume in the treatment planning, and not to exceed 15 cm3 of rectal volume receiving

  17. Sustained immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine administered as a two-dose schedule in adolescent girls: Five-year clinical data and modeling predictions from a randomized study

    PubMed Central

    Romanowski, Barbara; Schwarz, Tino F; Ferguson, Linda; Peters, Klaus; Dionne, Marc; Behre, Ulrich; Schulze, Karin; Hillemanns, Peter; Suryakiran, Pemmaraju; Thomas, Florence; Struyf, Frank

    2016-01-01

    In this randomized, partially-blind study (clinicaltrials.gov; NCT00541970), the licensed formulation of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (20 μg each of HPV-16/18 antigens) was found highly immunogenic up to 4 y after first vaccination, whether administered as a 2-dose (2D) schedule in girls 9–14 y or 3-dose (3D) schedule in women 15–25 y. This end-of-study analysis extends immunogenicity and safety data until Month (M) 60, and presents antibody persistence predictions estimated by piecewise and modified power law models. Healthy females (age stratified: 9–14, 15–19, 20–25 y) were randomized to receive 2D at M0,6 (N = 240 ) or 3D at M0,1,6 (N = 239). Here, results are reported for girls 9–14 y (2D) and women 15–25 y (3D). Seropositivity rates, geometric mean titers (by enzyme-linked immunosorbent assay) and geometric mean titer ratios (GMRs; 3D/2D; post-hoc exploratory analysis) were calculated. All subjects seronegative pre-vaccination in the according-to-protocol immunogenicity cohort were seropositive for anti-HPV-16 and −18 at M60. Antibody responses elicited by the 2D and 3D schedules were comparable at M60, with GMRs close to 1 (anti-HPV-16: 1.13 [95% confidence interval: 0.82–1.54]; anti-HPV-18: 1.06 [0.74–1.51]). Statistical modeling predicted that in 95% of subjects, antibodies induced by 2D and 3D schedules could persist above natural infection levels for ≥ 21 y post-vaccination. The vaccine had a clinically acceptable safety profile in both groups. In conclusion, a 2D M0,6 schedule of the HPV-16/18 AS04-adjuvanted vaccine was immunogenic for up to 5 y in 9–14 y-old girls. Statistical modeling predicted that 2D-induced antibodies could persist for longer than 20 y. PMID:26176261

  18. Optimization of dosing regimens and dosing in special populations.

    PubMed

    Sime, F B; Roberts, M S; Roberts, J A

    2015-10-01

    Treatment of infectious diseases is becoming increasingly challenging with the emergence of less-susceptible organisms that are poorly responsive to existing antibiotic therapies, and the unpredictable pharmacokinetic alterations arising from complex pathophysiologic changes in some patient populations. In view of this fact, there has been a progressive work on novel dose optimization strategies to renew the utility of forgotten old antibiotics and to improve the efficacy of those currently in use. This review summarizes the different approaches of optimization of antibiotic dosing regimens and the special patient populations which may benefit most from these approaches. The existing methods are based on monitoring of antibiotic concentrations and/or use of clinical covariates. Measured concentrations can be correlated with predefined pharmacokinetic/pharmacodynamic targets to guide clinicians in predicting the necessary dose adjustment. Dosing nomograms are also available to relate observed concentrations or clinical covariates (e.g. creatinine clearance) with optimal dosing. More precise dose prediction based on observed covariates is possible through the application of population pharmacokinetic models. However, the most accurate estimation of individualized dosing requirements is achieved through Bayesian forecasting which utilizes both measured concentration and clinical covariates. Various software programs are emerging to ease clinical application. Whilst more studies are warranted to clarify the clinical outcomes associated with the different dose optimization approaches, severely ill patients in the course of marked infections and/or inflammation including those with sepsis, septic shock, severe trauma, burns injury, major surgery, febrile neutropenia, cystic fibrosis, organ dysfunction and obesity are those groups which may benefit most from individualized dosing.

  19. The importance of depression and alcohol use in coronary artery bypass graft surgery patients: risk factors for delirium and poorer quality of life

    PubMed Central

    Humphreys, Joanne M; Denson, Linley A; Baker, Robert A; Tully, Phillip J

    2016-01-01

    Objective To investigate whether depression, anxiety and stress increase the risk for delirium and poor quality of life (QOL) after coronary artery bypass (CABG) surgery. Methods A total of 180 CABG patients (mean age of 63.5 ± 10.1 years, 82.2% males) completed baseline and postoperative self-report questionnaires to assess distress and QOL. Incident delirium was diagnosed postoperatively with a structured clinical interview and patients were monitored every day post-operatively for confusion and disturbance in consciousness. Results Delirium developed in 63 persons (35% of sample). After adjustment for covariates, delirium was significantly associated with depression [odds ratio (OR): 1.08; 95% confidence interval (CI): 1.03–1.13, P = 0.003], anxiety (OR: 1.07; 95% CI: 1.02–1.13, P = 0.01) and stress (OR: 1.05; 95% CI: 1.00–1.09, P = 0.03). Preoperative depression scores were associated with poorer QOL including bodily pain (β = −0.39, P = 0.013), vitality (β = −0.32, P = 0.020), social functioning (β = −0.51, P ≤ 0.001), emotional role function (β = −0.44, P = 0.003) and general health (β = −0.33, P = 0.038). Among the covariates, harmful levels of alcohol use was consistently associated with poorer QOL. Conclusions Depression and harmful levels of alcohol use were consistently associated with poorer QOL whereas depression, anxiety and stress were associated with delirium risk. These findings point to further research examining depression and harmful levels of alcohol use in coronary heart disease populations undergoing coronary revascularization. PMID:26918013

  20. Attachment forces of ants measured with a centrifuge: better 'wax-runners' have a poorer attachment to a smooth surface.

    PubMed

    Federle, W; Rohrseitz, K; Hölldobler, B

    2000-02-01

    The symbiotic ant partners of glaucous Macaranga ant-plants show an exceptional capacity to run on the slippery epicuticular wax crystals covering the plant stem without any difficulty. We test the hypothesis that these specialised 'wax-runners' have a general, superior attachment capacity. We compared attachment on a smooth surface for 11 ant species with different wax-running capacities. The maximum force that could be withstood before an ant became detached was quantified using a centrifuge recorded by a high-speed video camera. This technique has the advantage of causing minimum disruption and allows measurements in very small animals. When strong centrifugal forces were applied, the ants showed a conspicuous 'freezing reflex' advantageous to attachment. Attachment forces differed strongly among the ant species investigated. This variation could not be explained by different surface area/weight ratios of smaller and larger ants. Within species, however, detachment force per body weight (F/W) scaled with the predicted value of W(-)(0.33), where W is body weight in newtons. Surprisingly, our results not only disprove the hypothesis that 'wax-runners' generally attach better but also provide evidence for the reverse effect. Superior 'wax-runners' (genera Technomyrmex and Crematogaster) did not cling better to smooth Perspex, but performed significantly worse than closely related congeners that are unable to climb up waxy stems. This suggests an inverse relationship between adaptations to run on wax and to attach to a smooth surface.

  1. CD1d expression in renal cell carcinoma is associated with higher relapse rates, poorer cancer-specific and overall survival

    PubMed Central

    Chong, Tsung Wen; Goh, Fera Yiqian; Sim, Mei Yi; Huang, Hong Hong; Thike, Daw Aye Aye; Lim, Weng Khong; Teh, Bin Tean; Tan, Puay Hoon

    2015-01-01

    Aims We hypothesised that CD1d expression in renal cell carcinoma (RCC) may play a role in modifying the host immune response. Our aims were to investigate the expression of CD1d and to correlate this with histopathology and clinical outcomes in a cohort study of patients with RCC. Methods Gene expression and tissue microarray studies on a panel of RCC tissue were performed. Clinicopathological correlation was analysed using χ2/Fisher's exact test. Relapse-free survival, cancer-specific survival and overall survival were calculated for both CD1d high and low expressors. Survival outcomes were estimated with the Kaplan–Meier method and compared using Cox regression analysis. Results Gene expression microarray showed significant expression of CD1d in RCC versus normal renal tissue. By immunohistochemistry, we found that CD1d expression significantly associated with tumour stage/grade, higher relapse rates, poorer cancer-specific and overall survival. Conclusions CD1d expression on RCC correlated with aggressive disease and poorer clinical outcomes. PMID:25477528

  2. Sugar-sweetened soft drinks are associated with poorer cognitive function in individuals with type 2 diabetes: the Maine-Syracuse Longitudinal Study.

    PubMed

    Crichton, Georgina E; Elias, Merrill F; Torres, Rachael V

    2016-04-01

    The importance of adequate nutrition on cognitive performance is well recognised. Greater intakes of soft drinks are associated with a higher risk for type 2 diabetes, as well as other cardiometabolic diseases. A few studies have specifically examined whether the intake of soft drinks may be related to cognitive function. The aim of this study was to investigate whether soft drink intakes, including both sugar-sweetened and diet beverages, are associated with cognitive function, with adjustment for cardiovascular, lifestyle and dietary factors, and stratified according to type 2 diabetes status. Cross-sectional analyses were undertaken using 803 community-dwelling participants, aged 23-98 years, from the Maine-Syracuse Longitudinal Study. Cognitive function was measured using an extensive battery of neuropsychological tests. Usual dietary intake of soft drinks was assessed using a FFQ. Stratification by type 2 diabetes indicated that a greater intake of sugar-sweetened soft drinks was significantly associated with poorer performance in visual spatial memory, working memory, scanning and tracking, executive function, the global composite and the Mini-Mental State Examination in diabetic individuals. These relations were not attenuated with statistical control for BMI and other cardiovascular, lifestyle and dietary factors. Diet soft drink intake was unrelated to cognitive performance. Frequent sugar-sweetened soft drink intake was associated with poorer cognitive performance, particularly in individuals with type 2 diabetes, but the underlying causal mechanisms are yet to be determined. Longitudinal studies are needed to clarify these findings and the underlying causal mechanisms.

  3. Poorer divided attention in children born very preterm can be explained by difficulty with each component task, not the executive requirement to dual-task.

    PubMed

    Delane, Louise; Campbell, Catherine; Bayliss, Donna M; Reid, Corinne; Stephens, Amelia; French, Noel; Anderson, Mike

    2016-03-09

    Children born very preterm (VP, ≤ 32 weeks) exhibit poor performance on tasks of executive functioning. However, it is largely unknown whether this reflects the cumulative impact of non-executive deficits or a separable impairment in executive-level abilities. A dual-task paradigm was used in the current study to differentiate the executive processes involved in performing two simple attention tasks simultaneously. The executive-level contribution to performance was indexed by the within-subject cost incurred to single-task performance under dual-task conditions, termed dual-task cost. The participants included 77 VP children (mean age: 7.17 years) and 74 peer controls (mean age: 7.16 years) who completed Sky Search (selective attention), Score (sustained attention) and Sky Search DT (divided attention) from the Test of Everyday Attention for Children. The divided-attention task requires the simultaneous performance of the selective- and sustained-attention tasks. The VP group exhibited poorer performance on the selective- and divided-attention tasks, and showed a strong trend toward poorer performance on the sustained-attention task. However, there were no significant group differences in dual-task cost. These results suggest a cumulative impact of vulnerable lower-level cognitive processes on dual-tasking or divided attention in VP children, and fail to support the hypothesis that VP children show a separable impairment in executive-level abilities.

  4. Dose Rate Effects in Linear Bipolar Transistors

    NASA Technical Reports Server (NTRS)

    Johnston, Allan; Swimm, Randall; Harris, R. D.; Thorbourn, Dennis

    2011-01-01

    Dose rate effects are examined in linear bipolar transistors at high and low dose rates. At high dose rates, approximately 50% of the damage anneals at room temperature, even though these devices exhibit enhanced damage at low dose rate. The unexpected recovery of a significant fraction of the damage after tests at high dose rate requires changes in existing test standards. Tests at low temperature with a one-second radiation pulse width show that damage continues to increase for more than 3000 seconds afterward, consistent with predictions of the CTRW model for oxides with a thickness of 700 nm.

  5. Prostate Specific Antigen (PSA) as Predicting Marker for Clinical Outcome and Evaluation of Early Toxicity Rate after High-Dose Rate Brachytherapy (HDR-BT) in Combination with Additional External Beam Radiation Therapy (EBRT) for High Risk Prostate Cancer.

    PubMed

    Ecke, Thorsten H; Huang-Tiel, Hui-Juan; Golka, Klaus; Selinski, Silvia; Geis, Berit Christine; Koswig, Stephan; Bathe, Katrin; Hallmann, Steffen; Gerullis, Holger

    2016-11-10

    High-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT) is a common treatment option for locally advanced prostate cancer (PCa). Seventy-nine male patients (median age 71 years, range 50 to 79) with high-risk PCa underwent HDR-BT following EBRT between December 2009 and January 2016 with a median follow-up of 21 months. HDR-BT was administered in two treatment sessions (one week interval) with 9 Gy per fraction using a planning system and the Ir192 treatment unit GammaMed Plus iX. EBRT was performed with CT-based 3D-conformal treatment planning with a total dose administration of 50.4 Gy with 1.8 Gy per fraction and five fractions per week. Follow-up for all patients was organized one, three, and five years after radiation therapy to evaluate early and late toxicity side effects, metastases, local recurrence, and prostate-specific antigen (PSA) value measured in ng/mL. The evaluated data included age, PSA at time of diagnosis, PSA density, BMI (body mass index), Gleason score, D'Amico risk classification for PCa, digital rectal examination (DRE), PSA value after one/three/five year(s) follow-up (FU), time of follow-up, TNM classification, prostate volume, and early toxicity rates. Early toxicity rates were 8.86% for gastrointestinal, and 6.33% for genitourinary side effects. Of all treated patients, 84.81% had no side effects. All reported complications in early toxicity were grade 1. PSA density at time of diagnosis (p = 0.009), PSA on date of first HDR-BT (p = 0.033), and PSA on date of first follow-up after one year (p = 0.025) have statistical significance on a higher risk to get a local recurrence during follow-up. HDR-BT in combination with additional EBRT in the presented design for high-risk PCa results in high biochemical control rates with minimal side-effects. PSA is a negative predictive biomarker for local recurrence during follow-up. A longer follow-up is needed to assess long-term outcome and toxicities.

  6. To Bleed or Not to Bleed. A Prediction Based on Individual Gene Profiling Combined With Dose-Volume Histogram Shapes in Prostate Cancer Patients Undergoing Three-Dimensional Conformal Radiation Therapy

    SciTech Connect

    Valdagni, Riccardo Rancati, Tiziana; Ghilotti, Marco; Cozzarini, Cesare; Vavassori, Vittorio; Fellin, Gianni; Fiorino, Claudio; Girelli, Giuseppe; Barra, Salvina; Zaffaroni, Nadia; Pierotti, Marco Alessandro; Gariboldi, Manuela

    2009-08-01

    Purpose: The main purpose of this work was to try to elucidate why, despite excellent rectal dose-volume histograms (DVHs), some patients treated for prostate cancer exhibit late rectal bleeding (LRB) and others with poor DVHs do not. Thirty-five genes involved in DNA repair/radiation response were analyzed in patients accrued in the AIROPROS 0101 trial, which investigated the correlation between LRB and dosimetric parameters. Methods and Materials: Thirty patients undergoing conformal radiotherapy with prescription doses higher than 70 Gy (minimum follow-up, 48 months) were selected: 10 patients in the low-risk group (rectal DVH with the percent volume of rectum receiving more than 70 Gy [V70Gy] < 20% and the percent volume of rectum receiving more than 50 Gy [V50Gy] < 55%) with Grade 2 or Grade 3 (G2-G3) LRB, 10 patients in the high-risk group (V70Gy > 25% and V50Gy > 60%) with G2-G3 LRB, and 10 patients in the high-risk group with no toxicity. Quantitative reverse-transcriptase polymerase chain reaction was performed on RNA from lymphoblastoid cell lines obtained from Epstein-Barr virus-immortalized peripheral-blood mononucleated cells and on peripheral blood mononucleated cells. Interexpression levels were compared by using the Kruskal-Wallis test. Results: Intergroup comparison showed many constitutive differences: nine genes were significantly down-regulated in the low-risk bleeder group vs. the high-risk bleeder and high-risk nonbleeder groups: AKR1B1 (p = 0.019), BAZ1B (p = 0.042), LSM7 (p = 0.0016), MRPL23 (p = 0.015), NUDT1 (p = 0.0031), PSMB4 (p = 0.079), PSMD1 (p = 0.062), SEC22L1 (p = 0.040), and UBB (p = 0.018). Four genes were significantly upregulated in the high-risk nonbleeder group than in the other groups: DDX17 (p = 0.048), DRAP1 (p = 0.0025), RAD23 (p = 0.015), and SRF (p = 0.024). For most of these genes, it was possible to establish a cut-off value that correctly classified most patients. Conclusions: The predictive value of sensitivity and

  7. Prostate Specific Antigen (PSA) as Predicting Marker for Clinical Outcome and Evaluation of Early Toxicity Rate after High-Dose Rate Brachytherapy (HDR-BT) in Combination with Additional External Beam Radiation Therapy (EBRT) for High Risk Prostate Cancer

    PubMed Central

    Ecke, Thorsten H.; Huang-Tiel, Hui-Juan; Golka, Klaus; Selinski, Silvia; Geis, Berit Christine; Koswig, Stephan; Bathe, Katrin; Hallmann, Steffen; Gerullis, Holger

    2016-01-01

    High-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT) is a common treatment option for locally advanced prostate cancer (PCa). Seventy-nine male patients (median age 71 years, range 50 to 79) with high-risk PCa underwent HDR-BT following EBRT between December 2009 and January 2016 with a median follow-up of 21 months. HDR-BT was administered in two treatment sessions (one week interval) with 9 Gy per fraction using a planning system and the Ir192 treatment unit GammaMed Plus iX. EBRT was performed with CT-based 3D-conformal treatment planning with a total dose administration of 50.4 Gy with 1.8 Gy per fraction and five fractions per week. Follow-up for all patients was organized one, three, and five years after radiation therapy to evaluate early and late toxicity side effects, metastases, local recurrence, and prostate-specific antigen (PSA) value measured in ng/mL. The evaluated data included age, PSA at time of diagnosis, PSA density, BMI (body mass index), Gleason score, D’Amico risk classification for PCa, digital rectal examination (DRE), PSA value after one/three/five year(s) follow-up (FU), time of follow-up, TNM classification, prostate volume, and early toxicity rates. Early toxicity rates were 8.86% for gastrointestinal, and 6.33% for genitourinary side effects. Of all treated patients, 84.81% had no side effects. All reported complications in early toxicity were grade 1. PSA density at time of diagnosis (p = 0.009), PSA on date of first HDR-BT (p = 0.033), and PSA on date of first follow-up after one year (p = 0.025) have statistical significance on a higher risk to get a local recurrence during follow-up. HDR-BT in combination with additional EBRT in the presented design for high-risk PCa results in high biochemical control rates with minimal side-effects. PSA is a negative predictive biomarker for local recurrence during follow-up. A longer follow-up is needed to assess long-term outcome and toxicities. PMID:27834929

  8. Poorer general health status in children is associated with being overweight or obese in Hawai'i: findings from the 2007 National Survey of Children's Health.

    PubMed

    Teranishi, Kristen; Hayes, Donald K; Iwaishi, Louise K; Fuddy, Loretta J

    2011-07-01

    Obesity is a widespread national issue that affects the health and well-being of millions of people; particular attention has been focused on the burden among children. The National Survey of Children's Health data from 2007 was used to examine the relationship of child health status and unhealthy weight (overweight/obese defined as body mass index in ≥ 85 th percentile) among 874 children aged 10 to 17 years of age in Hawai'i. In particular, the parentally reported child's general health status was assessed comparing those with a poorer health status (defined as "good/fair/poor") to those with a better one (defined as "excellent/very good"). Descriptive analysis and multiple logistic regression analysis examined risk for overweight/obese with child's general health status, accounting for gender, race, and socioeconomic factors. More children with a poorer health status (46.5%; 95%CI=33.2-60.2) were overweight/obese compared to those of better health status (25.8%; 95%CI=21.9-30.2). Estimates of overweight/obese were high in Native Hawaiian/Pacific Islander (38.6%; 95%CI: 28.9-49.4), multiracial (30.9%; 95%CI=24.2-38.6) children, and children whose parents had less than 12 years education (56.8%; 95%CI=32.8-78.0). Multivariate logistic regression modeling showed a 2.92 (95%CI=1.52-5.61) greater odds for overweight/obese status in children with a poorer health status compared to those of better health status after accounting for age, race, gender, and parental education. Gender, race, and parental education were also significant factors associated with overweight/obese in the final adjusted model. It is important that children that are overweight or obese receive appropriate health screenings including assessments of general health status. Children in high risk socioeconomic groups should be a particular focus of prevention efforts to promote health equity and provide opportunities for children to reach their potential.

  9. Prediction of drug terminal half-life and terminal volume of distribution after intravenous dosing based on drug clearance, steady-state volume of distribution, and physiological parameters of the body.

    PubMed

    Berezhkovskiy, Leonid M

    2013-02-01

    The steady state, V(ss), terminal volume of distribution, V(β), and the terminal half-life, t(1/2), are commonly obtained from the drug plasma concentration-time profile, C(p)(t), following intravenous dosing. Unlike V(ss) that can be calculated based on the physicochemical properties of drugs considering the equilibrium partitioning between plasma and organ tissues, t(1/2) and V(β) cannot be calculated that way because they depend on the rates of drug transfer between blood and tissues. Considering the physiological pharmacokinetic model pertinent to the terminal phase of drug elimination, a novel equation that calculates t(1/2) (and consequently V(β)) was derived. It turns out that V(ss), the total body clearance, Cl, equilibrium blood-plasma concentration ratio, r; and the physiological parameters of the body such as cardiac output, and blood and tissue volumes are sufficient for determination of terminal kinetics. Calculation of t(1/2) by the obtained equation appears to be in good agreement with the experimentally observed vales of this parameter in pharmacokinetic studies in rat, monkey, dog, and human. The equation for the determination of the pre-exponent of the terminal phase of C(p)(t) is also found. The obtained equation allows to predict t(1/2) in human assuming that V(ss) and Cl were either obtained by allometric scaling or, respectively, calculated in silico or based on in vitro drug stability measurements. For compounds that have high clearance, the derived equation may be applied to calculate r just using the routine data on Cl, V(ss), and t(1/2), rather than doing the in vitro assay to measure this parameter.

  10. Peripheral doses from pediatric IMRT

    SciTech Connect

    Klein, Eric E.; Maserang, Beth; Wood, Roy; Mansur, David

    2006-07-15

    Peripheral dose (PD) data exist for conventional fields ({>=}10 cm) and intensity-modulated radiotherapy (IMRT) delivery to standard adult-sized phantoms. Pediatric peripheral dose reports are limited to conventional therapy and are model based. Our goal was to ascertain whether data acquired from full phantom studies and/or pediatric models, with IMRT treatment times, could predict Organ at Risk (OAR) dose for pediatric IMRT. As monitor units (MUs) are greater for IMRT, it is expected IMRT PD will be higher; potentially compounded by decreased patient size (absorption). Baseline slab phantom peripheral dose measurements were conducted for very small field sizes (from 2 to 10 cm). Data were collected at distances ranging from 5 to 72 cm away from the field edges. Collimation was either with the collimating jaws or the multileaf collimator (MLC) oriented either perpendicular or along the peripheral dose measurement plane. For the clinical tests, five patients with intracranial or base of skull lesions were chosen. IMRT and conventional three-dimensional (3D) plans for the same patient/target/dose (180 cGy), were optimized without limitation to the number of fields or wedge use. Six MV, 120-leaf MLC Varian axial beams were used. A phantom mimicking a 3-year-old was configured per Center for Disease Control data. Micro (0.125 cc) and cylindrical (0.6 cc) ionization chambers were appropriated for the thyroid, breast, ovaries, and testes. The PD was recorded by electrometers set to the 10{sup -10} scale. Each system set was uniquely calibrated. For the slab phantom studies, close peripheral points were found to have a higher dose for low energy and larger field size and when MLC was not deployed. For points more distant from the field edge, the PD was higher for high-energy beams. MLC orientation was found to be inconsequential for the small fields tested. The thyroid dose was lower for IMRT delivery than that predicted for conventional (ratio of IMRT/cnventional ranged

  11. Using chi-Squared Automatic Interaction Detection (CHAID) modelling to identify groups of methadone treatment clients experiencing significantly poorer treatment outcomes.

    PubMed

    Murphy, Emma L; Comiskey, Catherine M

    2013-10-01

    In times of scarce resources it is important for services to make evidence based decisions when identifying clients with poor outcomes. chi-Squared Automatic Interaction Detection (CHAID) modelling was used to identify characteristics of clients experiencing statistically significant poor outcomes. A national, longitudinal study recruited and interviewed, using the Maudsley Addiction Profile (MAP), 215 clients starting methadone treatment and 78% were interviewed one year later. Four CHAID analyses were conducted to model the interactions between the primary outcome variable, used heroin in the last 90 days prior to one year interview and variables on drug use, treatment history, social functioning and demographics. Results revealed that regardless of these other variables, males over 22 years of age consistently demonstrated significantly poorer outcomes than all other clients. CHAID models can be easily applied by service providers to provide ongoing evidence on clients exhibiting poor outcomes and requiring priority within services.

  12. [Formula: see text]Higher cortisol is associated with poorer executive functioning in preschool children: The role of parenting stress, parent coping and quality of daycare.

    PubMed

    Wagner, Shannon L; Cepeda, Ivan; Krieger, Dena; Maggi, Stefania; D'Angiulli, Amedeo; Weinberg, Joanne; Grunau, Ruth E

    2016-01-01

    Child executive functions (cognitive flexibility, inhibitory control, working memory) are key to success in school. Cortisol, the primary stress hormone, is known to affect cognition; however, there is limited information about how child cortisol levels, parenting factors and child care context relate to executive functions in young children. The aim of this study was to examine relationships between child cortisol, parenting stress, parent coping, and daycare quality in relation to executive functions in children aged 3-5 years. We hypothesized that (1) poorer executive functioning would be related to higher child cortisol and higher parenting stress, and (2) positive daycare quality and positive parent coping style would buffer the effects of child cortisol and parenting stress on executive functions. A total of 101 children (53 girls, 48 boys, mean age 4.24 years ±0.74) with complete data on all measures were included. Three saliva samples to measure cortisol were collected at the child's daycare/preschool in one morning. Parents completed the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P), Parenting Stress Index (PSI), and Ways of Coping Questionnaire (WCQ). The Early Childhood Environment Rating Scale - Revised (ECERS-R) was used to measure the quality of daycare. It was found that children with poorer executive functioning had higher levels of salivary cortisol, and their parents reported higher parenting stress. However, parent coping style and quality of daycare did not modulate these relationships. Identifying ways to promote child executive functioning is an important direction for improving school readiness.

  13. The H3.3 K27M mutation results in a poorer prognosis in brainstem gliomas than thalamic gliomas in adults.

    PubMed

    Feng, Jie; Hao, Shuyu; Pan, Changcun; Wang, Yu; Wu, Zhen; Zhang, Junting; Yan, Hai; Zhang, Liwei; Wan, Hong

    2015-11-01

    Brainstem and thalamic gliomas are rare, and they are poorly understood in adults. Genetic aberrations that occur in these tumors are still unknown. In this study, we investigated whether thalamic gliomas have different genetic aberrations and clinical outcomes compared with brainstem gliomas in adults. Forty-three glioma samples were selected, including 28 brainstem and 15 thalamic gliomas. The frequency of the K27M mutation in adult midline gliomas was 58.1%. High-grade gliomas in the thalamus were statistically significantly more numerous than brainstem gliomas. Patients with K27M mutant brainstem gliomas had a significantly shorter overall survival than patients with wild-type tumors (P = .020) by Cox regression after adjustment for other independent risk factors. However, there was no statistical tendency toward a poorer overall survival in thalamic gliomas containing the K27M mutation compared with wild-type tumors. The presence of the K27M mutation significantly corresponded with mutations in TP53 in thalamic gliomas. Interestingly, the K27M mutation was mutually exclusive with mutations in IDH1, which was detected only in brainstem gliomas. The microarray data identified 86 differentially expressed genes between brainstem and thalamic gliomas with the K27M mutation. The cyclin-dependent kinase 6 (CDK6) gene, which plays an important role in cancer pathways, was found to be differentially expressed between brainstem and thalamic gliomas with K27M mutations. Although the K27M mutation was frequently observed in adult brainstem and thalamic gliomas, this mutation tended to be associated with a poorer prognosis in brainstem gliomas but not in thalamic gliomas. Brainstem gliomas may present different genetic aberrations from thalamic gliomas. These differences may provide guidance for therapeutic decisions for the treatment of adult brainstem and thalamic gliomas, which may have different molecular targets.

  14. Higher LPA2 and LPA6 mRNA Levels in Hepatocellular Carcinoma Are Associated with Poorer Differentiation, Microvascular Invasion and Earlier Recurrence with Higher Serum Autotaxin Levels

    PubMed Central

    Ikeda, Hitoshi; Kurano, Makoto; Sato, Masaya; Kudo, Hiroki; Maki, Harufumi; Koike, Kazuhiko; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

    2016-01-01

    Hepatocellular carcinoma (HCC) commonly develops in patients with liver fibrosis; in these patients, the blood levels of lysophosphatidic acid (LPA) and its generating enzyme autotaxin (ATX) increase with the liver fibrosis stage. We aimed to examine the potential relevance of ATX and LPA in HCC. Fifty-eight HCC patients who underwent surgical treatment were consecutively enrolled in the study. Among the LPA receptors in HCC, higher LPA2 mRNA levels correlated with poorer differentiation, and higher LPA6 mRNA levels correlated with microvascular invasion, which suggested a higher malignant potential of HCC with increased LPA2 and LPA6 expression. In patients with primary HCC, neither LPA2 nor LPA6 mRNA levels were associated with recurrence. However, when serum ATX levels were combined for analysis as a surrogate for plasma LPA levels, the cumulative intra-hepatic recurrence rate was higher in patients in whom both serum ATX levels and LPA2 or LPA6 mRNA levels were higher than the median. However, the mRNA level of phosphatidic acid-selective phospholipase A1ɑ, another LPA-generating enzyme, in HCC patients was not associated with pathological findings or recurrence, even in combination with the expression of LPA receptors. Higher LPA2 mRNA levels were associated with poorer differentiation, and higher LPA6 levels were associated with microvascular invasion in HCC; both became a risk factor for recurrence after surgical treatment when combined with increased serum ATX levels. ATX and LPA receptors merit consideration as therapeutic targets of HCC. PMID:27583415

  15. Higher cortisol is associated with poorer executive functioning in preschool children: The role of parenting stress, parent coping and quality of daycare

    PubMed Central

    Wagner, Shannon L.; Cepeda, Ivan; Krieger, Dena; Maggi, Stefania; D’Angiulli, Amedeo; Weinberg, Joanne; Grunau, Ruth E.

    2016-01-01

    Child executive functions (cognitive flexibility, inhibitory control, working memory) are key to success in school. Cortisol, the primary stress hormone, is known to affect cognition; however, there is limited information about how child cortisol levels, parenting factors and child care context relate to executive functions in young children. The aim of this study was to examine relationships between child cortisol, parenting stress, parent coping, and daycare quality in relation to executive functions in children aged 3–5 years. We hypothesized that (1) poorer executive functioning would be related to higher child cortisol and higher parenting stress, and (2) positive daycare quality and positive parent coping style would buffer the effects of child cortisol and parenting stress on executive functions. A total of 101 children (53 girls, 48 boys, mean age 4.24 years ±0.74) with complete data on all measures were included. Three saliva samples to measure cortisol were collected at the child’s daycare/preschool in one morning. Parents completed the Behavior Rating Inventory of Executive Function – Preschool Version (BRIEF-P), Parenting Stress Index (PSI), and Ways of Coping Questionnaire (WCQ). The Early Childhood Environment Rating Scale – Revised (ECERS-R) was used to measure the quality of daycare. It was found that children with poorer executive functioning had higher levels of salivary cortisol, and their parents reported higher parenting stress. However, parent coping style and quality of daycare did not modulate these relationships. Identifying ways to promote child executive functioning is an important direction for improving school readiness. PMID:26335047

  16. Acoustic dose and acoustic dose-rate.

    PubMed

    Duck, Francis

    2009-10-01

    Acoustic dose is defined as the energy deposited by absorption of an acoustic wave per unit mass of the medium supporting the wave. Expressions for acoustic dose and acoustic dose-rate are given for plane-wave conditions, including temporal and frequency dependencies of energy deposition. The relationship between the acoustic dose-rate and the resulting temperature increase is explored, as is the relationship between acoustic dose-rate and radiation force. Energy transfer from the wave to the medium by means of acoustic cavitation is considered, and an approach is proposed in principle that could allow cavitation to be included within the proposed definitions of acoustic dose and acoustic dose-rate.

  17. Absorbed Dose and Dose Equivalent Calculations for Modeling Effective Dose

    NASA Technical Reports Server (NTRS)

    Welton, Andrew; Lee, Kerry

    2010-01-01

    While in orbit, Astronauts are exposed to a much higher dose of ionizing radiation than when on the ground. It is important to model how shielding designs on spacecraft reduce radiation effective dose pre-flight, and determine whether or not a danger to humans is presented. However, in order to calculate effective dose, dose equivalent calculations are needed. Dose equivalent takes into account an absorbed dose of radiation and the biological effectiveness of ionizing radiation. This is important in preventing long-term, stochastic radiation effects in humans spending time in space. Monte carlo simulations run with the particle transport code FLUKA, give absorbed and equivalent dose data for relevant shielding. The shielding geometry used in the dose calculations is a layered slab design, consisting of aluminum, polyethylene, and water. Water is used to simulate the soft tissues that compose the human body. The results obtained will provide information on how the shielding performs with many thicknesses of each material in the slab. This allows them to be directly applicable to modern spacecraft shielding geometries.

  18. SU-E-T-280: Reconstructed Rectal Wall Dose Map-Based Verification of Rectal Dose Sparing Effect According to Rectum Definition Methods and Dose Perturbation by Air Cavity in Endo-Rectal Balloon

    SciTech Connect

    Park, J; Park, H; Lee, J; Kang, S; Lee, M; Suh, T; Lee, B

    2014-06-01

    Purpose: Dosimetric effect and discrepancy according to the rectum definition methods and dose perturbation by air cavity in an endo-rectal balloon (ERB) were verified using rectal-wall (Rwall) dose maps considering systematic errors in dose optimization and calculation accuracy in intensity-modulated radiation treatment (IMRT) for prostate cancer patients. Methods: When the inflated ERB having average diameter of 4.5 cm and air volume of 100 cc is used for patient, Rwall doses were predicted by pencil-beam convolution (PBC), anisotropic analytic algorithm (AAA), and AcurosXB (AXB) with material assignment function. The errors of dose optimization and calculation by separating air cavity from the whole rectum (Rwhole) were verified with measured rectal doses. The Rwall doses affected by the dose perturbation of air cavity were evaluated using a featured rectal phantom allowing insert of rolled-up gafchromic films and glass rod detectors placed along the rectum perimeter. Inner and outer Rwall doses were verified with reconstructed predicted rectal wall dose maps. Dose errors and extent at dose levels were evaluated with estimated rectal toxicity. Results: While AXB showed insignificant difference of target dose coverage, Rwall doses underestimated by up to 20% in dose optimization for the Rwhole than Rwall at all dose range except for the maximum dose. As dose optimization for Rwall was applied, the Rwall doses presented dose error less than 3% between dose calculation algorithm except for overestimation of maximum rectal dose up to 5% in PBC. Dose optimization for Rwhole caused dose difference of Rwall especially at intermediate doses. Conclusion: Dose optimization for Rwall could be suggested for more accurate prediction of rectal wall dose prediction and dose perturbation effect by air cavity in IMRT for prostate cancer. This research was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea

  19. Evaluation of Rectal Dose During High-Dose-Rate Intracavitary Brachytherapy for Cervical Carcinoma

    SciTech Connect

    Sha, Rajib Lochan; Reddy, Palreddy Yadagiri; Rao, Ramakrishna; Muralidhar, Kanaparthy R.; Kudchadker, Rajat J.

    2011-01-01

    High-dose-rate intracavitary brachytherapy (HDR-ICBT) for carcinoma of the uterine cervix often results in high doses being delivered to surrounding organs at risk (OARs) such as the rectum and bladder. Therefore, it is important to accurately determine and closely monitor the dose delivered to these OARs. In this study, we measured the dose delivered to the rectum by intracavitary applications and compared this measured dose to the International Commission on Radiation Units and Measurements rectal reference point dose calculated by the treatment planning system (TPS). To measure the dose, we inserted a miniature (0.1 cm{sup 3}) ionization chamber into the rectum of 86 patients undergoing radiation therapy for cervical carcinoma. The response of the miniature chamber modified by 3 thin lead marker rings for identification purposes during imaging was also characterized. The difference between the TPS-calculated maximum dose and the measured dose was <5% in 52 patients, 5-10% in 26 patients, and 10-14% in 8 patients. The TPS-calculated maximum dose was typically higher than the measured dose. Our study indicates that it is possible to measure the rectal dose for cervical carcinoma patients undergoing HDR-ICBT. We also conclude that the dose delivered to the rectum can be reasonably predicted by the TPS-calculated dose.

  20. Parameterization of solar flare dose

    SciTech Connect

    Lamarche, A.H.; Poston, J.W.

    1996-12-31

    A critical aspect of missions to the moon or Mars will be the safety and health of the crew. Radiation in space is a hazard for astronauts, especially high-energy radiation following certain types of solar flares. A solar flare event can be very dangerous if astronauts are not adequately shielded because flares can deliver a very high dose in a short period of time. The goal of this research was to parameterize solar flare dose as a function of time to see if it was possible to predict solar flare occurrence, thus providing a warning time. This would allow astronauts to take corrective action and avoid receiving a dose greater than the recommended limit set by the National Council on Radiation Protection and Measurements (NCRP).

  1. Predicting Attrition: A Test of Alternative Approaches

    DTIC Science & Technology

    1977-03-01

    entry to the poorer riskEs. There are two bases for screening. The first one is actuarial . With a sufficiently large recruit cohort, actual loss rates...predicting attrition overcome the drawbacks of the actuarial approach. They let us know what the significant combinations of characteristics are that...terms of their character- istics and average first-year attrition rate, which was about 17.5 percent. Then, each of the four approaches or models was

  2. Does childhood adversity account for poorer mental and physical health in second-generation Irish people living in Britain? Birth cohort study from Britain (NCDS)

    PubMed Central

    Das-Munshi, Jayati; Clark, Charlotte; Dewey, Michael E; Leavey, Gerard; Stansfeld, Stephen A; Prince, Martin J

    2013-01-01

    Objectives Worldwide, the Irish diaspora experience elevated mortality and morbidity across generations, not accounted for through socioeconomic position. The main objective of the present study was to assess if childhood disadvantage accounts for poorer mental and physical health in adulthood, in second-generation Irish people. Design Analysis of prospectively collected birth cohort data, with participants followed to midlife. Setting England, Scotland and Wales. Participants Approximately 17 000 babies born in a single week in 1958. Six per cent of the cohort were of second-generation Irish descent. Outcomes Primary outcomes were common mental disorders assessed at age 44/45 and self-rated health at age 42. Secondary outcomes were those assessed at ages 23 and 33. Results Relative to the rest of the cohort, second-generation Irish children grew up in marked material and social disadvantage, which tracked into early adulthood. By midlife, parity was reached between second-generation Irish cohort members and the rest of the sample on most disadvantage indicators. At age 23, Irish cohort members were more likely to screen positive for common mental disorders (OR 1.44; 95% CI 1.06 to 1.94). This had reduced slightly by midlife (OR 1.27; 95% CI 0.96 to 1.69). Although at age 23 second-generation cohort members were just as likely to report poorer self-rated health (OR 1.06; 95% CI 0.79 to 1.43), by midlife this difference had increased (OR 1.25; 95% CI 0.98 to 1.60). Adjustment for childhood and early adulthood adversity fully attenuated differences in adult health disadvantages. Conclusions Social and material disadvantage experienced in childhood continues to have long-range adverse effects on physical and mental health at midlife, in second-generation Irish cohort members. This suggests important mechanisms over the life-course, which may have important policy implications in the settlement of migrant families. PMID:23457320

  3. Comparison of TID Effects in Space-Like Variable Dose Rates and Constant Dose Rates

    NASA Technical Reports Server (NTRS)

    Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Evans, Robin W.; Jun, Insoo

    2008-01-01

    The degradation of the LM193 dual voltage comparator has been studied at different TID dose rate profiles, including several different constant dose rates and a variable dose rate that simulates the behavior of a solar flare. A comparison of results following constant dose rate vs. variable dose rates is made to explore how well the constant dose rates used for typical part testing predict the performance during a simulated space-like mission. Testing at a constant dose rate equal to the lowest dose rate seen during the simulated flare provides an extremely conservative estimate of the overall amount of degradation. A constant dose rate equal to the average dose rate is also more conservative than the variable rate. It appears that, for this part, weighting the dose rates by the amount of total dose received at each rate (rather than the amount of time at each dose rate) results in an average rate that produces an amount of degradation that is a reasonable approximation to that received by the variable rate.

  4. High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Aβ deposition in an Alzheimer mouse model.

    PubMed

    Lubitz, Irit; Ricny, Jan; Atrakchi-Baranes, Dana; Shemesh, Chen; Kravitz, Efrat; Liraz-Zaltsman, Sigal; Maksin-Matveev, Anna; Cooper, Itzik; Leibowitz, Avshalom; Uribarri, Jaime; Schmeidler, James; Cai, Weijing; Kristofikova, Zdena; Ripova, Daniela; LeRoith, Derek; Schnaider-Beeri, Michal

    2016-04-01

    There is growing evidence of the involvement of advanced glycation end products (AGEs) in the pathogenesis of neurodegenerative processes including Alzheimer's disease (AD) and their function as a seed for the aggregation of Aβ, a hallmark feature of AD. AGEs are formed endogenously and exogenously during heating and irradiation of foods. We here examined the effect of a diet high in AGEs in the context of an irradiated diet on memory, insoluble Aβ42 , AGEs levels in hippocampus, on expression of the receptor for AGEs (RAGE), and on oxidative stress in the vasculature. We found that AD-like model mice on high-AGE diet due to irradiation had significantly poorer memory, higher hippocampal levels of insoluble Aβ42 and AGEs as well as higher levels of oxidative stress on vascular walls, compared to littermates fed an isocaloric diet. These differences were not due to weight gain. The data were further supported by the overexpression of RAGE, which binds to Aβ42 and regulates its transport across the blood-brain barrier, suggesting a mediating pathway. Because exposure to AGEs can be diminished, these insights provide an important simple noninvasive potential therapeutic strategy for alleviating a major lifestyle-linked disease epidemic.

  5. The prognosis was poorer in colorectal cancers that expressed both VEGF and PROK1 (No correlation coefficient between VEGF and PROK1).

    PubMed

    Goi, Takanori; Nakazawa, Toshiyuki; Hirono, Yasuo; Yamaguchi, Akio

    2015-10-06

    The angiogenic proteins vascular endothelial growth factor (VEGF) and prokineticin1 (PROK1) proteins are considered important in colorectal cancer, the relationship between their simultaneous expression and prognosis was investigated in the present study. VEGF and PROK1 expression in 620 primary human colorectal cancer lesions was confirmed via immunohistochemical staining with anti-VEGF and anti-PROK1 antibodies, and the correlation between the expression of these 2 proteins and recurrence/prognosis were investigated. VEGF protein was expressed in 329 (53.1%) and PROK1 protein was expressed in 223 (36.0%). PROK1 and VEGF were simultaneously expressed in 116 (18.7%) of the 620 cases. The correlation coefficient between VEGF expression and PROK1 expression was r = 0.11, and therefore correlation was not observed. Clinical pathology revealed that substantially lymphnode matastasis, hematogenous metastasis, or TMN advanced-stage IV was significantly more prevalent in cases that expressed both VEGF and PROK1 than in the cases negative for both proteins or those positive for only 1 of the proteins. Also the cases positive for both proteins exhibited the worst recurrence and prognosis. In the Cox proportional hazards model, VEGF and PROK1 expression was an independent prognostic factor. The prognosis was poorer in colorectal cancers that expressed both PROK1 and VEGF relative to the cases that expressed only 1 protein, and the expression of both proteins was found to be an independent prognostic factor.

  6. LoColms: an innovative approach of enhancing traditional classroom form of education by promoting web-based distance learning in the poorer countries.

    PubMed

    Ngarambe, Donart; Pan, Yun-he; Chen, De-ren

    2003-01-01

    There have been numerous attempts recently to promote technology based education (Shrestha, 1997) in the poorer third world countries, but so far all these have not provided a sustainable solution as they are either centered and controlled from abroad and relying solely on foreign donors for their sustenance or they are not web-based, which make distribution problematic, and some are not affordable by most of the local population in these places. In this paper we discuss an application, the Local College Learning Management System (LoColms), which we are developing, that is both sustainable and economical to suit the situation in these countries. The application is a web-based system, and aims at improving the traditional form of education by empowering the local universities. Its economy comes from the fact that it is supported by traditional communication technology, the public switching telephone network system, PSTN, which eliminates the need for packet switched or dedicated private virtual networks (PVN) usually required in similar situations. At a later stage, we shall incorporate ontology and paging tools to improve resource sharing and storage optimization in the Proxy Caches (ProCa) and LoColms servers. The system is based on the client/server paradigm and its infrastructure consists of the PSTN, ProCa, with the learning centers accessing the universities by means of point-to-point protocol (PPP).

  7. Delinquency in incarcerated male adolescents is associated with single parenthood, exposure to more violence at home and in the community, and poorer self-image

    PubMed Central

    Erdelja, Stanislava; Vokal, Petra; Bolfan, Marija; Erdelja, Sergej Augustin; Begovac, Branka; Begovac, Ivan

    2013-01-01

    Aim To assess the relationships between delinquency and demographic and family variables, academic performance, war stressors, home/community, school, and media violence exposure, self-image, and psychopathology. Methods This cross-sectional study included 100 delinquent, incarcerated male adolescents and 100 matched schoolchildren from Croatia. It lasted from January 2008 to June 2009, and used socio-demographic questionnaire, questionnaire on children’s stressful and traumatic war experiences, exposure to violence scale, the Offer Self-Image Questionnaire, and Youth Self-Report Questionnaire. Results Logistic regression analysis showed that delinquency in incarcerated adolescents was more likely related to having parents who did not live together (odds ratio [OR] 2.40; confidence interval [CI] 1.18-4.90, P = 0.015), being more exposed to violence at home/community (OR 3.84; CI 1.58-9.34, P = 0.003), and having poorer self-image (OR 1.09; CI = 1.03-1.16, P < 0.002). Conclusion Preventive and therapeutic interventions in incarcerated delinquents should be specifically targeted toward single parenthood, family factors, trauma oriented interventions, and focused on multiple dimensions of self-concept of adolescents. PMID:24170725

  8. Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses

    PubMed Central

    Colborn, Theo; Hayes, Tyrone B.; Heindel, Jerrold J.; Jacobs, David R.; Lee, Duk-Hee; Shioda, Toshi; Soto, Ana M.; vom Saal, Frederick S.; Welshons, Wade V.; Zoeller, R. Thomas

    2012-01-01

    For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health. PMID:22419778

  9. There is no safe dose of prions.

    PubMed

    Fryer, Helen R; McLean, Angela R

    2011-01-01

    Understanding the circumstances under which exposure to transmissible spongiform encephalopathies (TSEs) leads to infection is important for managing risks to public health. Based upon ideas in toxicology and radiology, it is plausible that exposure to harmful agents, including TSEs, is completely safe if the dose is low enough. However, the existence of a threshold, below which infection probability is zero has never been demonstrated experimentally. Here we explore this question by combining data and mathematical models that describe scrapie infections in mice following experimental challenge over a broad range of doses. We analyse data from 4338 mice inoculated at doses ranging over ten orders of magnitude. These data are compared to results from a within-host model in which prions accumulate according to a stochastic birth-death process. Crucially, this model assumes no threshold on the dose required for infection. Our data reveal that infection is possible at the very low dose of a 1000 fold dilution of the dose that infects half the challenged animals (ID50). Furthermore, the dose response curve closely matches that predicted by the model. These findings imply that there is no safe dose of prions and that assessments of the risk from low dose exposure are right to assume a linear relationship between dose and probability of infection. We also refine two common perceptions about TSE incubation periods: that their mean values decrease linearly with logarithmic decreases in dose and that they are highly reproducible between hosts. The model and data both show that the linear decrease in incubation period holds only for doses above the ID50. Furthermore, variability in incubation periods is greater than predicted by the model, not smaller. This result poses new questions about the sources of variability in prion incubation periods. It also provides insight into the limitations of the incubation period assay.

  10. A novel dose uncertainty model and its application for dose verification.

    PubMed

    Jin, Hosang; Chung, Heetaek; Liu, Chihray; Palta, Jatinder; Suh, Tae-Suk; Kim, Siyong

    2005-06-01

    Based on statistical approach, a novel dose uncertainty model was introduced considering both nonspatial and spatial dose deviations. Non-space-oriented uncertainty is mainly caused by dosimetric uncertainties, and space-oriented dose uncertainty is the uncertainty caused by all spatial displacements. Assuming these two parts are independent, dose difference between measurement and calculation is a linear combination of nonspatial and spatial dose uncertainties. Two assumptions were made: (1) the relative standard deviation of nonspatial dose uncertainty is inversely proportional to the dose standard deviation sigma, and (2) the spatial dose uncertainty is proportional to the gradient of dose. The total dose uncertainty is a quadratic sum of the nonspatial and spatial uncertainties. The uncertainty model provides the tolerance dose bound for comparison between calculation and measurement. In the statistical uncertainty model based on a Gaussian distribution, a confidence level of 3sigma theoretically confines 99.74% of measurements within the bound. By setting the confidence limit, the tolerance bound for dose comparison can be made analogous to that of existing dose comparison methods (e.g., a composite distribution analysis, a gamma test, a chi evaluation, and a normalized agreement test method). However, the model considers the inherent dose uncertainty characteristics of the test points by taking into account the space-specific history of dose accumulation, while the previous methods apply a single tolerance criterion to the points, although dose uncertainty at each point is significantly different from others. Three types of one-dimensional test dose distributions (a single large field, a composite flat field made by two identical beams, and three-beam intensity-modulated fields) were made to verify the robustness of the model. For each test distribution, the dose bound predicted by the uncertainty model was compared with simulated measurements. The simulated

  11. Dose optimization tool

    NASA Astrophysics Data System (ADS)

    Amir, Ornit; Braunstein, David; Altman, Ami

    2003-05-01

    A dose optimization tool for CT scanners is presented using patient raw data to calculate noise. The tool uses a single patient image which is modified for various lower doses. Dose optimization is carried out without extra measurements by interactively visualizing the dose-induced changes in this image. This tool can be used either off line, on existing image(s) or, as a pre - requisite for dose optimization for the specific patient, during the patient clinical study. The algorithm of low-dose simulation consists of reconstruction of two images from a single measurement and uses those images to create the various lower dose images. This algorithm enables fast simulation of various low dose (mAs) images on a real patient image.

  12. Is assessment of anti-Müllerian hormone and/or antral follicle count useful in the prediction of ovarian response in expected normal responders treated with a fixed dose of recombinant FSH and GnRH antagonists? A prospective observational study.

    PubMed

    Ganidou, Maria A; Kolibianakis, Efstratios M; Venetis, Christos A; Gerou, Spiros; Makedos, Georgios A; Klearchou, Nikolaos; Tarlatzis, Basil C

    2014-11-01

    The purpose of this prospective observational study was to evaluate whether the assessment of AMH and AFC is useful in the prediction of ovarian response in expected normal responders treated with a fixed dose of recombinant FSH (rec-FSH) and GnRH antagonists. A base model including age and basal FSH as independent predictors of COCs could explain 15% of the variance observed in the number of COCs retrieved (p = 0.002). The addition of AFC did not increase significantly the predictive ability of the above model, whereas the addition of AMH increased the performance of the base model by 13% (p < 0.001). Logistic regression analysis showed that only when AMH was added to the base model, including age and FSH, its predictive capacity for high ovarian response was statistically significant (F-test: p = 0.001; c-statistic: 0.80, 95% CI: 0.70-0.88), but this was not the case for poor ovarian response. In conclusion, the addition of AMH, but not of AFC, to a model including female age and basal FSH, is useful in the prediction of ovarian response in expected normal responders treated with a fixed dose of recombinant FSH and GnRH antagonists.

  13. Habitual fat intake predicts memory function in younger women.

    PubMed

    Gibson, E Leigh; Barr, Suzanne; Jeanes, Yvonne M

    2013-01-01

    High intakes of fat have been linked to greater cognitive decline in old age, but such associations may already occur in younger adults. We tested memory and learning in 38 women (25 to 45 years old), recruited for a larger observational study in women with polycystic ovary syndrome. These women varied in health status, though not significantly between cases (n = 23) and controls (n = 15). Performance on tests sensitive to medial temporal lobe function (CANTABeclipse, Cambridge Cognition Ltd, Cambridge, UK), i.e., verbal memory, visuo-spatial learning, and delayed pattern matching (DMS), were compared with intakes of macronutrients from 7-day diet diaries and physiological indices of metabolic syndrome. Partial correlations were adjusted for age, activity, and verbal IQ (National Adult Reading Test). Greater intakes of saturated and trans fats, and higher saturated to unsaturated fat ratio (Sat:UFA), were associated with more errors on the visuo-spatial task and with poorer word recall and recognition. Unexpectedly, higher UFA intake predicted poorer performance on the word recall and recognition measures. Fasting insulin was positively correlated with poorer word recognition only, whereas higher blood total cholesterol was associated only with visuo-spatial learning errors. None of these variables predicted performance on a DMS test. The significant nutrient-cognition relationships were tested for mediation by total energy intake: saturated and trans fat intakes, and Sat:UFA, remained significant predictors specifically of visuo-spatial learning errors, whereas total fat and UFA intakes now predicted only poorer word recall. Examination of associations separately for monounsaturated (MUFA) and polyunsaturated fats suggested that only MUFA intake was predictive of poorer word recall. Saturated and trans fats, and fasting insulin, may already be associated with cognitive deficits in younger women. The findings need extending but may have important implications for

  14. Multilineage dysplasia is associated with a poorer prognosis in patients with de novo acute myeloid leukemia with intermediate-risk cytogenetics and wild-type NPM1.

    PubMed

    Rozman, María; Navarro, José-Tomás; Arenillas, Leonor; Aventín, Anna; Giménez, Teresa; Alonso, Esther; Perea, Granada; Camós, Mireia; Navarrete, Mayda; Tuset, Esperanza; Florensa, Lourdes; Millá, Fuensanta; Nomdedéu, Josep; de la Banda, Esmeralda; Díaz-Beyá, Marina; Pratcorona, Marta; Garrido, Ana; Navarro, Blanca; Brunet, Salut; Sierra, Jorge; Esteve, Jordi

    2014-10-01

    Acute myeloid leukemia (AML) with myelodysplasia-related changes is characterized by the presence of multilineage dysplasia (MLD), frequently related to high-risk cytogenetics and poor outcome. However, the presence of MLD does not modify the favorable prognostic impact of NPM1 mutation. The prognosis of patients with AML presenting marked dysplasia lacking high-risk cytogenetics and NPM1 mutation is uncertain. We evaluated the prognostic impact of MLD in 177 patients with intermediate-risk cytogenetics AML (IR-AML) and wild-type NPM1. Patients were categorized as MLD-WHO (WHO myelodysplasia criteria; n = 43, 24 %), MLD-NRW (significant MLD non-reaching WHO criteria; n = 16, 9 %), absent MLD (n = 80, 45 %), or non-evaluable MLD (n = 38, 22 %). No differences concerning the main characteristics were observed between patients with or without MLD. Outcome of patients with MLD-WHO and MLD-NRW was similar, and significantly worse than patients lacking MLD. The presence of MLD (66 vs. 80 %, p = 0.03; HR, 95 % CI = 2.3, 1.08-4.08) and higher leukocyte count at diagnosis was the only variable associated with lower probability of complete remission after frontline therapy. Concerning survival, age and leukocytes showed an independent prognostic value, whereas MLD showed a trend to a negative impact (p = 0.087, HR, 95 % CI = 1.426, 0.95-2.142). Moreover, after excluding patients receiving an allogeneic stem cell transplantation in first CR, MLD was associated with a shorter survival (HR, 95 % CI = 1.599, 1.026-2.492; p = 0.038). In conclusion, MLD identifies a subgroup of patients with poorer outcome among patients with IR-AML and wild-type NPM1.

  15. Malignant ileocaecal serotonin-producing carcinoid tumours: the presence of a solid growth pattern and/or Ki67 index above 1% identifies patients with a poorer prognosis.

    PubMed

    Cunningham, Janet L; Grimelius, Lars; Sundin, Anders; Agarwal, Smriti; Janson, Eva T

    2007-01-01

    Patients with malignant serotonin-producing carcinoid tumours in the jejunum, ileum and caecum generally have long survival expectancy. In some patients, however, tumour progression is more rapid and there is a need to identify them at an early stage. The purpose of this study was to determine if histopathological characteristics and/or Ki67 and apoptotic indices are of prognostic value in cases of metastatic disease. Eighty-one patients with this tumour were included in the study; all had metastases and their survival range was 1-223 months. Five growth patterns were identified and described. For 57 patients whose tumour material was available, the Ki67 and apoptotic indices were calculated for ten randomly selected tumour areas and 'hot spots'. A Cox regression analysis was used to test if histopathology and/or Ki67 index >/=1% could identify patients whose survival might be shorter than anticipated. One of the histopathological growth patterns-the solid (non-organoid) cell pattern-was correlated to shorter survival in both primary tumours and metastases, when compared with the organoid growth patterns (hazard ratio 2.9 and 2.3, p/=1%, in both primary tumour and metastases, identified patients at increased risk of shorter survival (hazard ratio 5.4 and 2.5, p/=1%, can be used to identify patients with a poorer prognosis. This study also showed that Ki67 index <2% cannot, as previously suggested, be used to indicate a benign progression for this tumour category.

  16. Validation and Modification of a Prediction Model for Acute Cardiac Events in Patients With Breast Cancer Treated With Radiotherapy Based on Three-Dimensional Dose Distributions to Cardiac Substructures.

    PubMed

    van den Bogaard, Veerle A B; Ta, Bastiaan D P; van der Schaaf, Arjen; Bouma, Angelique B; Middag, Astrid M H; Bantema-Joppe, Enja J; van Dijk, Lisanne V; van Dijk-Peters, Femke B J; Marteijn, Laurens A W; de Bock, Gertruida H; Burgerhof, Johannes G M; Gietema, Jourik A; Langendijk, Johannes A; Maduro, John H; Crijns, Anne P G

    2017-01-17

    Purpose A relationship between mean heart dose (MHD) and acute coronary event (ACE) rate was reported in a study of patients with breast cancer (BC). The main objective of our cohort study was to validate this relationship and investigate if other dose-distribution parameters are better predictors for ACEs than MHD. Patients and Methods The cohort consisted of 910 consecutive female patients with BC treated with radiotherapy (RT) after breast-conserving surgery. The primary end point was cumulative incidence of ACEs within 9 years of follow-up. Both MHD and various dose-distribution parameters of the cardiac substructures were collected from three-dimensional computed tomography planning data. Results The median MHD was 2.37 Gy (range, 0.51 to 15.25 Gy). The median follow-up time was 7.6 years (range, 0.1 to 10.1 years), during which 30 patients experienced an ACE. The cumulative incidence of ACE increased by 16.5% per Gy (95% CI, 0.6 to 35.0; P = .042). Analysis showed that the volume of the left ventricle receiving 5 Gy (LV-V5) was the most important prognostic dose-volume parameter. The most optimal multivariable normal tissue complication probability model for ACEs consisted of LV-V5, age, and weighted ACE risk score per patient (c-statistic, 0.83; 95% CI, 0.75 to 0.91). Conclusion A significant dose-effect relationship was found for ACEs within 9 years after RT. Using MHD, the relative increase per Gy was similar to that reported in the previous study. In addition, LV-V5 seemed to be a better predictor for ACEs than MHD. This study confirms the importance of reducing exposure of the heart to radiation to avoid excess risk of ACEs after radiotherapy for BC.

  17. Anxious distress predicts subsequent treatment outcome and side effects in depressed patients starting antidepressant treatment.

    PubMed

    Gaspersz, Roxanne; Lamers, Femke; Kent, Justine M; Beekman, Aartjan T F; Smit, Johannes H; van Hemert, Albert M; Schoevers, Robert A; Penninx, Brenda W J H

    2017-01-01

    Evidence has shown that the DSM-5 anxious distress specifier captures a clinically valid construct that predicts a worse clinical course. Although of importance for treatment planning and monitoring, however, the specifier's ability to predict treatment outcome is unknown. This is the first study to examine the ability of the DSM-5 anxious distress specifier to predict treatment response and side effects in depressed patients who recently initiated antidepressant treatment. Patients were from the Netherlands Study of Depression and Anxiety, an ongoing longitudinal cohort study. Baseline, 1-year and 2-year follow-up data were used from 149 patients (18-65 years) with current Major Depressive Disorder (MDD) who recently started adequately dosed antidepressant medication. Five self-report items were used to construct the DSM-5 anxious distress specifier. Treatment outcomes were depression severity after 1 year and 2 years, remission of MDD after 2 years and antidepressant side effects during treatment. For comparison, analyses were repeated for comorbid DSM-IV-based anxiety disorders as a predictor. In depressed patients who received antidepressant treatment, the anxious distress specifier (prevalence = 59.1%) significantly predicted higher severity (1 year: B = 1.94, P = 0.001; 2 years: B = 1.63, P = 0.001), lower remission rates (OR = 0.44, P = 0.0496) and greater frequency of side effects (≥4 vs. 0: OR = 2.74, P = 0.061). In contrast, the presence of comorbid anxiety disorders did not predict these treatment outcomes. The anxious distress specifier significantly predicts poorer treatment outcomes as shown by higher depression severity, lower remission rates, and greater frequency of antidepressant side effects in patients with MDD on adequate antidepressant treatment. Therefore, this simple 5-item specifier is of potential great clinical usefulness for treatment planning and monitoring in depressed patients.

  18. Curtailing patient-specific IMRT QA procedures from 2D dose error distribution

    PubMed Central

    Kurosu, Keita; Sumida, Iori; Mizuno, Hirokazu; Otani, Yuki; Oda, Michio; Isohashi, Fumiaki; Seo, Yuji; Suzuki, Osamu; Ogawa, Kazuhiko

    2016-01-01

    A patient-specific quality assurance (QA) test is conducted to verify the accuracy of dose delivery. It generally consists of three verification processes: the absolute point dose difference, the planar dose differences at each gantry angle, and the planar dose differences by 3D composite irradiation. However, this imposes a substantial workload on medical physicists. The objective of this study was to determine whether our novel method that predicts the 3D delivered dose allows certain patient-specific IMRT QAs to be curtailed. The object was IMRT QA for the pelvic region with regard to point dose and composite planar dose differences. We compared measured doses, doses calculated in the treatment planning system, and doses predicted by in-house software. The 3D predicted dose was reconstructed from the per-field measurement by incorporating the relative dose error distribution into the original dose grid of each beam. All point dose differences between the measured and the calculated dose were within ±3%, whereas 93.3% of them between the predicted and the calculated dose were within ±3%. As for planar dose differences, the gamma passing rates between the calculated and the predicted dose were higher than those between the calculated and the measured dose. Comparison and statistical analysis revealed a correlation between the predicted and the measured dose with regard to both point dose and planar dose differences. We concluded that the prediction-based approach is an accurate substitute for the conventional measurement-based approach in IMRT QA for the pelvic region. Our novel approach will help medical physicists save time on IMRT QA. PMID:26661854

  19. Curtailing patient-specific IMRT QA procedures from 2D dose error distribution.

    PubMed

    Kurosu, Keita; Sumida, Iori; Mizuno, Hirokazu; Otani, Yuki; Oda, Michio; Isohashi, Fumiaki; Seo, Yuji; Suzuki, Osamu; Ogawa, Kazuhiko

    2016-06-01

    A patient-specific quality assurance (QA) test is conducted to verify the accuracy of dose delivery. It generally consists of three verification processes: the absolute point dose difference, the planar dose differences at each gantry angle, and the planar dose differences by 3D composite irradiation. However, this imposes a substantial workload on medical physicists. The objective of this study was to determine whether our novel method that predicts the 3D delivered dose allows certain patient-specific IMRT QAs to be curtailed. The object was IMRT QA for the pelvic region with regard to point dose and composite planar dose differences. We compared measured doses, doses calculated in the treatment planning system, and doses predicted by in-house software. The 3D predicted dose was reconstructed from the per-field measurement by incorporating the relative dose error distribution into the original dose grid of each beam. All point dose differences between the measured and the calculated dose were within ±3%, whereas 93.3% of them between the predicted and the calculated dose were within ±3%. As for planar dose differences, the gamma passing rates between the calculated and the predicted dose were higher than those between the calculated and the measured dose. Comparison and statistical analysis revealed a correlation between the predicted and the measured dose with regard to both point dose and planar dose differences. We concluded that the prediction-based approach is an accurate substitute for the conventional measurement-based approach in IMRT QA for the pelvic region. Our novel approach will help medical physicists save time on IMRT QA.

  20. A Meta-Analysis of Retention in Methadone Maintenance by Dose and Dosing Strategy

    PubMed Central

    Bao, Yan-ping; Liu, Zhi-min; Epstein, David H.; Du, Cun; Shi, Jie; Lu, Lin

    2013-01-01

    Objective To estimate, via meta-analysis, the influence of different methadone dose ranges and dosing strategies on retention rates in methadone maintenance treatment (MMT). Methods A systematic literature search identified 18 randomized controlled trials (RCTs) evaluating methadone dose and retention. Retention was defined as the percentage of patients remaining in treatment at a specified time point. After initial univariate analyses of retention by Pearson chi-squares, we used multilevel logistic regression to calculate summary odds ratios (ORs) and 95% confidence intervals for the effects of methadone dose (above or below 60 mg/day), flexible vs. fixed dosing strategy, and duration of follow-up. Results The total number of opioid-dependent participants in the 18 studies was 2831, with 1797 in MMT and 1034 receiving alternative mediations or placebo. Each variable significantly predicted retention with the other variables controlled for. Retention was greater with methadone doses ≥ 60 than with doses <60 (OR: 1.74, 95% CI: 1.43–2.11). Similarly, retention was greater with flexible-dose strategies than with fixed-dose strategies (OR: 1.72, 95% CI: 1.41–2.11). Conclusions Higher doses of methadone and individualization of doses are each independently associated with better retention in MMT. PMID:19152203

  1. Revisiting Warfarin Dosing Using Machine Learning Techniques

    PubMed Central

    Sharabiani, Ashkan; Bress, Adam; Douzali, Elnaz; Darabi, Houshang

    2015-01-01

    Determining the appropriate dosage of warfarin is an important yet challenging task. Several prediction models have been proposed to estimate a therapeutic dose for patients. The models are either clinical models which contain clinical and demographic variables or pharmacogenetic models which additionally contain the genetic variables. In this paper, a new methodology for warfarin dosing is proposed. The patients are initially classified into two classes. The first class contains patients who require doses of >30 mg/wk and the second class contains patients who require doses of ≤30 mg/wk. This phase is performed using relevance vector machines. In the second phase, the optimal dose for each patient is predicted by two clinical regression models that are customized for each class of patients. The prediction accuracy of the model was 11.6 in terms of root mean squared error (RMSE) and 8.4 in terms of mean absolute error (MAE). This was 15% and 5% lower than IWPC and Gage models (which are the most widely used models in practice), respectively, in terms of RMSE. In addition, the proposed model was compared with fixed-dose approach of 35 mg/wk, and the model proposed by Sharabiani et al. and its outperformance were proved in terms of both MAE and RMSE. PMID:26146514

  2. Dose convolution filter: Incorporating spatial dose information into tissue response modeling

    SciTech Connect

    Huang Yimei; Joiner, Michael; Zhao Bo; Liao Yixiang; Burmeister, Jay

    2010-03-15

    Purpose: A model is introduced to integrate biological factors such as cell migration and bystander effects into physical dose distributions, and to incorporate spatial dose information in plan analysis and optimization. Methods: The model consists of a dose convolution filter (DCF) with single parameter {sigma}. Tissue response is calculated by an existing NTCP model with DCF-applied dose distribution as input. The authors determined {sigma} of rat spinal cord from published data. The authors also simulated the GRID technique, in which an open field is collimated into many pencil beams. Results: After applying the DCF, the NTCP model successfully fits the rat spinal cord data with a predicted value of {sigma}=2.6{+-}0.5 mm, consistent with 2 mm migration distances of remyelinating cells. Moreover, it enables the appropriate prediction of a high relative seriality for spinal cord. The model also predicts the sparing of normal tissues by the GRID technique when the size of each pencil beam becomes comparable to {sigma}. Conclusions: The DCF model incorporates spatial dose information and offers an improved way to estimate tissue response from complex radiotherapy dose distributions. It does not alter the prediction of tissue response in large homogenous fields, but successfully predicts increased tissue tolerance in small or highly nonuniform fields.

  3. Neutron dose equivalent meter

    DOEpatents

    Olsher, Richard H.; Hsu, Hsiao-Hua; Casson, William H.; Vasilik, Dennis G.; Kleck, Jeffrey H.; Beverding, Anthony

    1996-01-01

    A neutron dose equivalent detector for measuring neutron dose capable of accurately responding to neutron energies according to published fluence to dose curves. The neutron dose equivalent meter has an inner sphere of polyethylene, with a middle shell overlying the inner sphere, the middle shell comprising RTV.RTM. silicone (organosiloxane) loaded with boron. An outer shell overlies the middle shell and comprises polyethylene loaded with tungsten. The neutron dose equivalent meter defines a channel through the outer shell, the middle shell, and the inner sphere for accepting a neutron counter tube. The outer shell is loaded with tungsten to provide neutron generation, increasing the neutron dose equivalent meter's response sensitivity above 8 MeV.

  4. ELDRS Characterization for a Very High Dose Mission

    NASA Technical Reports Server (NTRS)

    Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Kenna, Aaron J.; Thorbourn, Dennis O.; Clark, Karla B.; Yan, Tsun-Yee

    2010-01-01

    Evaluation of bipolar linear parts which may have Enhanced Low Dose Rate Sensitivity (ELDRS) is problematic for missions that have very high dose radiation requirements. The accepted standards for evaluating parts that display ELDRS require testing at a very low dose rate which could be prohibitively long for very high dose missions. In this work, a methodology for ELDRS characterization of bipolar parts for mission doses up to 1 Mrad(Si) is evaluated. The procedure employs an initial dose rate of 0.01 rad(Si)/s to a total dose of 50 krad(Si) and then changes to 0.04 rad(Si)/s to a total dose of 1 Mrad(Si). This procedure appears to work well. No change in rate of degradation with dose has been observed when the dose rate is changed from 0.01 to 0.04 rad(Si)/s. This is taken as an indication that the degradation due to the higher dose rate is equivalent to that at the lower dose rate at the higher dose levels, at least for the parts studied to date. In several cases, significant parameter degradation or functional failure not observed at HDR was observed at fairly high total doses (50 to 250 krad(Si)) at LDR. This behavior calls into question the use of dose rate trend data and enhancement factors to predict LDR performance.

  5. Calculation of effective dose.

    PubMed

    McCollough, C H; Schueler, B A

    2000-05-01

    The concept of "effective dose" was introduced in 1975 to provide a mechanism for assessing the radiation detriment from partial body irradiations in terms of data derived from whole body irradiations. The effective dose is the mean absorbed dose from a uniform whole-body irradiation that results in the same total radiation detriment as from the nonuniform, partial-body irradiation in question. The effective dose is calculated as the weighted average of the mean absorbed dose to the various body organs and tissues, where the weighting factor is the radiation detriment for a given organ (from a whole-body irradiation) as a fraction of the total radiation detriment. In this review, effective dose equivalent and effective dose, as established by the International Commission on Radiological Protection in 1977 and 1990, respectively, are defined and various methods of calculating these quantities are presented for radionuclides, radiography, fluoroscopy, computed tomography and mammography. In order to calculate either quantity, it is first necessary to estimate the radiation dose to individual organs. One common method of determining organ doses is through Monte Carlo simulations of photon interactions within a simplified mathematical model of the human body. Several groups have performed these calculations and published their results in the form of data tables of organ dose per unit activity or exposure. These data tables are specified according to particular examination parameters, such as radiopharmaceutical, x-ray projection, x-ray beam energy spectra or patient size. Sources of these organ dose conversion coefficients are presented and differences between them are examined. The estimates of effective dose equivalent or effective dose calculated using these data, although not intended to describe the dose to an individual, can be used as a relative measure of stochastic radiation detriment. The calculated values, in units of sievert (or rem), indicate the amount of

  6. Radiotherapy dose calculations in the presence of hip prostheses

    SciTech Connect

    Keall, Paul J.; Siebers, Jeffrey V.; Jeraj, Robert; Mohan, Radhe

    2003-06-30

    The high density and atomic number of hip prostheses for patients undergoing pelvic radiotherapy challenge our ability to accurately calculate dose. A new clinical dose calculation algorithm, Monte Carlo, will allow accurate calculation of the radiation transport both within and beyond hip prostheses. The aim of this research was to investigate, for both phantom and patient geometries, the capability of various dose calculation algorithms to yield accurate treatment plans. Dose distributions in phantom and patient geometries with high atomic number prostheses were calculated using Monte Carlo, superposition, pencil beam, and no-heterogeneity correction algorithms. The phantom dose distributions were analyzed by depth dose and dose profile curves. The patient dose distributions were analyzed by isodose curves, dose-volume histograms (DVHs) and tumor control probability/normal tissue complication probability (TCP/NTCP) calculations. Monte Carlo calculations predicted the dose enhancement and reduction at the proximal and distal prosthesis interfaces respectively, whereas superposition and pencil beam calculations did not. However, further from the prosthesis, the differences between the dose calculation algorithms diminished. Treatment plans calculated with superposition showed similar isodose curves, DVHs, and TCP/NTCP as the Monte Carlo plans, except in the bladder, where Monte Carlo predicted a slightly lower dose. Treatment plans calculated with either the pencil beam method or with no heterogeneity correction differed significantly from the Monte Carlo plans.

  7. Biologically Based Dose-Response Modeling. What is the potential for accurate description of the biological linkages in the applied dose - tissue dose-health effect continuum?

    EPA Science Inventory

    Given knowledge of exposure, the shape of the dose response curve is the key to predicting health risk, which in turn determines allowable levels of exposure and the associated economic costs of compliance.

  8. Antemortem Prediction of Braak Stage

    PubMed Central

    Carlson, Jesper O. E.; Gatz, Margaret; Pedersen, Nancy L.; Graff, Caroline; Nennesmo, Inger; Lindström, Anna-Karin; Gerritsen, Lotte

    2015-01-01

    We examined the extent to which tauopathy distribution, as determined by Braak staging, might be predicted by various risk factors in older individuals. The Swedish Twin Registry provided extensive information on neuropsychological function, lifestyle and cardiovascular risk factors of 128 patients for whom autopsy data including Braak staging were available. Logistic regression was used to develop a prognostic model that targeted discrimination between Braak stages 0-II vs. III-VI. The analysis showed that Braak stage III-VI was significantly predicted by having one or more APOE ε4 alleles, older age, high total cholesterol, absence of diabetes and cardiovascular disease, and poorer scores on the Wechsler Adult Intelligence Score Information test, verbal fluency, and recognition memory but better verbal recall. The algorithm predicted Braak stage III-VI well (receiver-operating characteristic area under curve: 0.897; 95% CI: 0.842-0.951). Using a cut-off of 50% risk or more, the sensitivity was 85%, the specificity was 70%, and the negative predictive value was 69%. This study demonstrates that tauopathy distribution can be accurately predicted using a combination of antemortem patient data. These results provide further insight into tauopathy development and AD-related disease mechanisms and suggest a prognostic model that predicts the spread of neurofibrillary tangles above the transentorhinal stage. PMID:26469248

  9. What Explains Divorced Women's Poorer Health? The Mediating Role of Health Insurance and Access to Health Care in a Rural Iowan Sample

    ERIC Educational Resources Information Center

    Lavelle, Bridget; Lorenz, Frederick O.; Wickrama, K. A. S.

    2012-01-01

    Economic restructuring in rural areas in recent decades has been accompanied by rising marital instability. To examine the implications of the increase in divorce for the health of rural women, we examine how marital status predicts adequacy of health insurance coverage and health care access, and whether these factors help to account for the…

  10. Simplified Warfarin Dose-response Pharmacodynamic Models

    PubMed Central

    Kim, Seongho; Gaweda, Adam E.; Wu, Dongfeng; Li, Lang; Rai, Shesh N.; Brier, Michael E.

    2014-01-01

    Warfarin is a frequently used oral anticoagulant for long-term prevention and treatment of thromboembolic events. Due to its narrow therapeutic range and large inter-individual dose-response variability, it is highly desirable to personalize warfarin dosing. However, the complexity of the conventional kinetic-pharmacodynamic (K-PD) models hampers the development of the personalized dose management. To avert this challenge, we propose simplified PD models for warfarin dose-response relationship, which is motivated by ideas from control theory. The simplified models were further applied to longitudinal data of 37 patients undergoing anticoagulation treatment using the standard two-stage approach and then compared with the conventional K-PD models. Data analysis shows that all models have a similar predictive ability, but the simplified models are most parsimonious. PMID:25750489

  11. Derivation of dose conversion factors for tritium

    SciTech Connect

    Killough, G. G.

    1982-03-01

    For a given intake mode (ingestion, inhalation, absorption through the skin), a dose conversion factor (DCF) is the committed dose equivalent to a specified organ of an individual per unit intake of a radionuclide. One also may consider the effective dose commitment per unit intake, which is a weighted average of organ-specific DCFs, with weights proportional to risks associated with stochastic radiation-induced fatal health effects, as defined by Publication 26 of the International Commission on Radiological Protection (ICRP). This report derives and tabulates organ-specific dose conversion factors and the effective dose commitment per unit intake of tritium. These factors are based on a steady-state model of hydrogen in the tissues of ICRP's Reference Man (ICRP Publication 23) and equilibrium of specific activities between body water and other tissues. The results differ by 27 to 33% from the estimate on which ICRP Publication 30 recommendations are based. The report also examines a dynamic model of tritium retention in body water, mineral bone, and two compartments representing organically-bound hydrogen. This model is compared with data from human subjects who were observed for extended periods. The manner of combining the dose conversion factors with measured or model-predicted levels of contamination in man's exposure media (air, drinking water, soil moisture) to estimate dose rate to an individual is briefly discussed.

  12. Determinants of Toxicity, Patterns of Failure, and Outcome Among Adult Patients With Soft Tissue Sarcomas of the Extremity and Superficial Trunk Treated With Greater Than Conventional Doses of Perioperative High-Dose-Rate Brachytherapy and External Beam Radiotherapy

    SciTech Connect

    San Miguel, Inigo; San Julian, Mikel; Cambeiro, Mauricio; Sanmamed, Miguel Fernandez; Vazquez-Garcia, Blanca; Pagola, Maria; Gaztanaga, Miren; Martin-Algarra, Salvador; Martinez-Monge, Rafael

    2011-11-15

    Purpose: The present study was undertaken to determine factors predictive of toxicity, patterns of failure, and survival in 60 adult patients with soft tissue sarcomas of the extremity and superficial trunk treated with combined perioperative high-dose-rate brachytherapy and external beam radiotherapy. Methods and Materials: The patients were treated with surgical resection and perioperative high-dose-rate brachytherapy (16 or 24 Gy) for negative and close/microscopically positive resection margins, respectively. External beam radiotherapy (45 Gy) was added postoperatively to reach a 2-Gy equivalent dose of 62.9 and 72.3 Gy, respectively. Adjuvant chemotherapy with ifosfamide and doxorubicin was given to patients with advanced high-grade tumors. Results: Grade 3 toxic events were observed in 18 patients (30%) and Grade 4 events in 6 patients (10%). No Grade 5 events were observed. A location in the lower limb was significant for Grade 3 or greater toxic events on multivariate analysis (p = .013), and the tissue volume encompassed by the 150% isodose line showed a trend toward statistical significance (p = .086). The local control, locoregional control, and distant control rate at 9 years was 77.4%, 69.5%, and 63.8%, respectively. On multivariate analysis, microscopically involved margins correlated with local control (p = .036) and locoregional control (p = .007) and tumor size correlated with distant metastases (p = .004). The 9-year disease-free survival and overall survival rate was 47.0% and 61.5%, respectively. Multivariate analysis showed poorer disease-free survival rates for patients with tumors >6 cm (p = .005) and microscopically involved margins (p = .043), and overall survival rates decreased with increasing tumor size (p = .011). Conclusions: Grade 3 or greater wound complications can probably be decreased using meticulous treatment planning to decrease the tissue volume encompassed by the 150% isodose line, especially in lower limb locations

  13. Rotation to methadone after opioid dose escalation: How should individualization of dosing occur?

    PubMed

    Zimmermann, Camilla; Seccareccia, Dori; Booth, Christopher M; Cottrell, Wayne

    2005-01-01

    Methadone is a synthetic opioid agonist and N-methyl-D-aspartate (NMDA) receptor antagonist that is being increasingly used in pain management, particularly for pain that is resistant to conventional opioids. We describe two patients with neurotoxic side effects on escalating doses of parenteral hydromorphone with uncontrolled cancer pain who were successfully converted to oral methadone at a dose much smaller than predicted. The phenomenon of increasing pain despite opioid dose escalation is discussed and the rationale for the use of methadone in this situation is described. While methadone is useful for patients with unremitting pain on another opioid, existing conversion regimens do not specifically take into account the setting of dose escalation. Clinical guidelines for rotation to methadone after dose escalation of the previous opioid are needed to avoid toxicity including respiratory depression. A possible conversion method for rotation to methadone for patients with escalating pain and opioid use is suggested.

  14. Strategy for stochastic dose-rate induced enhanced elimination of malignant tumour without dose escalation.

    PubMed

    Paul, Subhadip; Roy, Prasun Kumar

    2016-09-01

    The efficacy of radiation therapy, a primary modality of cancer treatment, depends in general upon the total radiation dose administered to the tumour during the course of therapy. Nevertheless, the delivered radiation also irradiates normal tissues and dose escalation procedure often increases the elimination of normal tissue as well. In this article, we have developed theoretical frameworks under the premise of linear-quadratic-linear (LQL) model using stochastic differential equation and Jensen's inequality for exploring the possibility of attending to the two therapeutic performance objectives in contraposition-increasing the elimination of prostate tumour cells and enhancing the relative sparing of normal tissue in fractionated radiation therapy, within a prescribed limit of total radiation dose. Our study predicts that stochastic temporal modulation in radiation dose-rate appreciably enhances prostate tumour cell elimination, without needing dose escalation in radiation therapy. However, constant higher dose-rate can also enhance the elimination of tumour cells. In this context, we have shown that the sparing of normal tissue with stochastic dose-rate is considerably more than the sparing of normal tissue with the equivalent constant higher dose-rate. Further, by contrasting the stochastic dose-rate effects under LQL and linear-quadratic (LQ) models, we have also shown that the LQ model over-estimates stochastic dose-rate effect in tumour and under-estimates the stochastic dose-rate effect in normal tissue. Our study indicates the possibility of utilizing stochastic modulation of radiation dose-rate for designing enhanced radiation therapy protocol for cancer.

  15. Electron beam dose calculations.

    PubMed

    Hogstrom, K R; Mills, M D; Almond, P R

    1981-05-01

    Electron beam dose distributions in the presence of inhomogeneous tissue are calculated by an algorithm that sums the dose distribution of individual pencil beams. The off-axis dependence of the pencil beam dose distribution is described by the Fermi-Eyges theory of thick-target multiple Coulomb scattering. Measured square-field depth-dose data serve as input for the calculations. Air gap corrections are incorporated and use data from'in-air' measurements in the penumbra of the beam. The effective depth, used to evaluate depth-dose, and the sigma of the off-axis Gaussian spread against depth are calculated by recursion relations from a CT data matrix for the material underlying individual pencil beams. The correlation of CT number with relative linear stopping power and relative linear scattering power for various tissues is shown. The results of calculations are verified by comparison with measurements in a 17 MeV electron beam from the Therac 20 linear accelerator. Calculated isodose lines agree nominally to within 2 mm of measurements in a water phantom. Similar agreement is observed in cork slabs simulating lung. Calculations beneath a bone substitute illustrate a weakness in the calculation. Finally a case of carcinoma in the maxillary antrum is studied. The theory suggests an alternative method for the calculation of depth-dose of rectangular fields.

  16. Radiation dose rates from UF{sub 6} cylinders

    SciTech Connect

    Friend, P.J.

    1991-12-31

    This paper describes the results of many studies, both theoretical and experimental, which have been carried out by Urenco over the last 15 years into radiation dose rates from uranium hexafluoride (UF{sub 6}) cylinders. The contents of the cylinder, its history, and the geometry all affect the radiation dose rate. These factors are all examined in detail. Actual and predicted dose rates are compared with levels permitted by IAEA transport regulations.

  17. Sexual victimization history predicts academic performance in college women.

    PubMed

    Baker, Majel R; Frazier, Patricia A; Greer, Christiaan; Paulsen, Jacob A; Howard, Kelli; Meredith, Liza N; Anders, Samantha L; Shallcross, Sandra L

    2016-11-01

    College women frequently report having experienced sexual victimization (SV) in their lifetime, including child sexual abuse and adolescent/adult sexual assault. Although the harmful mental health sequelae of SV have been extensively studied, recent research suggests that SV is also a risk factor for poorer college academic performance. The current studies examined whether exposure to SV uniquely predicted poorer college academic performance, even beyond contributions from three well-established predictors of academic performance: high school rank, composite standardized test scores (i.e., American College Testing [ACT]), and conscientiousness. Study 1 analyzed longitudinal data from a sample of female college students (N = 192) who were assessed at the beginning and end of one semester. SV predicted poorer cumulative end-of-semester grade point average (GPA) while controlling for well-established predictors of academic performance. Study 2 replicated these findings in a second longitudinal study of female college students (N = 390) and extended the analyses to include follow-up data on the freshmen and sophomore students (n = 206) 4 years later. SV predicted students' GPA in their final term at the university above the contributions of well-established academic predictors, and it was the only factor related to leaving college. These findings highlight the importance of expanding the scope of outcomes of SV to include academic performance, and they underscore the need to assess SV and other adverse experiences on college campuses to target students who may be at risk of poor performance or leaving college. (PsycINFO Database Record

  18. High-dose chemoradiotherapy (HDC) in the Ewing family of tumors (EFT).

    PubMed

    Burdach, S; Jürgens, H

    2002-02-01

    EFT is defined by the expression of ews/ets fusion genes. The type of the fusion transcript impacts on the clinical biology. EFT requires risk adapted treatment. A risk-adapted treatment is determined by tumor localisation, tumor stage and volume. For metastatic and relapsed disease the pattern of spread and the time of relapse are the determinants of risk stratification. Staging of Ewing tumors has been considerably improved by magnetic resonance imaging and modern isotope scanning techniques. However, the determination of the extent of the metastatic spread in particular number of involved bones remains an unresolved issue. The prognosis for high-risk Ewing tumors has been improved by multimodal and high-dose radio/chemotherapy (HDC). The concepts for high-dose therapy in Ewing tumors are based on dose response and dose intensity relationships. In single agent HDC most experience exists with Melphalan. Several chemotherapeutic agents have been used in combination HDC with or without TBI such as Adriamycin, BCNU, Busulphan, Carboplatin, Cyclophosphamide, Etoposide, Melphalan, Thiotepa Procarbazin and Vincristine. To date, superiority of any high-dose chemotherapy regimen has not been established. However, the clinical biology, the pattern of spread and the time of relapse determine the prognosis of patient who are eligible for HDC. In particular, patients with multifocal bone or bone marrow metastases have a poorer prognosis than patients with lung metastases. In addition, patients with a relapse within 24 months have a poorer prognosis than patients with a relapse later than 24 months after diagnosis. This review will analyze the results of single- and multi-agent chemotherapy with respect to agent combination, dose and risk stratum of patient population. Future therapeutic modalities for the treatment of EFT might encompass immunotherapeutic and genetic strategies including allogeneic stem cell transplantation.

  19. Utirik Atoll Dose Assessment

    SciTech Connect

    Robison, W.L.; Conrado, C.L.; Bogen, K.T

    1999-10-06

    On March 1, 1954, radioactive fallout from the nuclear test at Bikini Atoll code-named BRAVO was deposited on Utirik Atoll which lies about 187 km (300 miles) east of Bikini Atoll. The residents of Utirik were evacuated three days after the fallout started and returned to their atoll in May 1954. In this report we provide a final dose assessment for current conditions at the atoll based on extensive data generated from samples collected in 1993 and 1994. The estimated population average maximum annual effective dose using a diet including imported foods is 0.037 mSv y{sup -1} (3.7 mrem y{sup -1}). The 95% confidence limits are within a factor of three of their population average value. The population average integrated effective dose over 30-, 50-, and 70-y is 0.84 mSv (84, mrem), 1.2 mSv (120 mrem), and 1.4 mSv (140 mrem), respectively. The 95% confidence limits on the population-average value post 1998, i.e., the 30-, 50-, and 70-y integral doses, are within a factor of two of the mean value and are independent of time, t, for t > 5 y. Cesium-137 ({sup 137}Cs) is the radionuclide that contributes most of this dose, mostly through the terrestrial food chain and secondarily from external gamma exposure. The dose from weapons-related radionuclides is very low and of no consequence to the health of the population. The annual background doses in the U. S. and Europe are 3.0 mSv (300 mrem), and 2.4 mSv (240 mrem), respectively. The annual background dose in the Marshall Islands is estimated to be 1.4 mSv (140 mrem). The total estimated combined Marshall Islands background dose plus the weapons-related dose is about 1.5 mSv y{sup -1} (150 mrem y{sup -1}) which can be directly compared to the annual background effective dose of 3.0 mSv y{sup -1} (300 mrem y{sup -1}) for the U. S. and 2.4 mSv y{sup -1} (240 mrem y{sup -1}) for Europe. Moreover, the doses listed in this report are based only on the radiological decay of {sup 137}Cs (30.1 y half-life) and other

  20. Photon dose calculation based on electron multiple-scattering theory: primary dose deposition kernels.

    PubMed

    Wang, L; Jette, D

    1999-08-01

    The transport of the secondary electrons resulting from high-energy photon interactions is essential to energy redistribution and deposition. In order to develop an accurate dose-calculation algorithm for high-energy photons, which can predict the dose distribution in inhomogeneous media and at the beam edges, we have investigated the feasibility of applying electron transport theory [Jette, Med. Phys. 15, 123 (1988)] to photon dose calculation. In particular, the transport of and energy deposition by Compton electron and electrons and positrons resulting from pair production were studied. The primary photons are treated as the source of the secondary electrons and positrons, which are transported through the irradiated medium using Gaussian multiple-scattering theory [Jette, Med. Phys. 15, 123 (1988)]. The initial angular and kinetic energy distribution(s) of the secondary electrons (and positrons) emanating from the photon interactions are incorporated into the transport. Due to different mechanisms of creation and cross-section functions, the transport of and the energy deposition by the electrons released in these two processes are studied and modeled separately based on first principles. In this article, we focus on determining the dose distribution for an individual interaction site. We define the Compton dose deposition kernel (CDK) or the pair-production dose deposition kernel (PDK) as the dose distribution relative to the point of interaction, per unit interaction density, for a monoenergetic photon beam in an infinite homogeneous medium of unit density. The validity of this analytic modeling of dose deposition was evaluated through EGS4 Monte Carlo simulation. Quantitative agreement between these two calculations of the dose distribution and the average energy deposited per interaction was achieved. Our results demonstrate the applicability of the electron dose-calculation method to photon dose calculation.

  1. Effects of injected dose, BMI and scanner type on NECR and image noise in PET imaging.

    PubMed

    Chang, Tingting; Chang, Guoping; Kohlmyer, Steve; Clark, John W; Rohren, Eric; Mawlawi, Osama R

    2011-08-21

    Noise equivalent count rate (NECR) and image noise are two different but related metrics that have been used to predict and assess image quality, respectively. The aim of this study is to investigate, using patient studies, the relationships between injected dose (ID), body mass index (BMI) and scanner type on NECR and image noise measurements in PET imaging. Two groups of 90 patients each were imaged on a GE DSTE and a DRX PET/CT scanner, respectively. The patients in each group were divided into nine subgroups according to three BMI (20-24.9, 25-29.9, 30-45 kg m(-2)) and three ID (296-444, 444-555, 555-740 MBq) ranges, resulting in ten patients/subgroup. All PET data were acquired in 3D mode and reconstructed using the VuePoint HD® fully 3D OSEM algorithm (2 iterations, 21(DRX) or 20 (DSTE) subsets). NECR and image noise measurements for bed positions covering the liver were calculated for each patient. NECR was calculated from the trues, randoms and scatter events recorded in the DICOM header of each patient study, while image noise was determined as the standard deviation of 50 non-neighboring voxels in the liver of each patient. A t-test compared the NECR and image noise for different scanners but with the same BMI and ID. An ANOVA test on the other hand was used to compare the results of patients with different BMI but the same ID and scanner type as well as different ID but the same BMI and scanner type. As expected the t-test showed a significant difference in NECR between the two scanners for all BMI and ID subgroups. However, contrary to what is expected no such findings were observed for image noise measurement. The ANOVA results showed a statistically significant difference in both NECR and image noise among the different BMI for each ID and scanner subgroup. However, there was no statistically significant difference in NECR and image noise across different ID for each BMI and scanner subgroup. Although the GE DRX PET/CT scanner has better count rate

  2. Long-term antibody persistence after vaccination with a 2-dose Havrix (inactivated hepatitis A vaccine): 20 years of observed data, and long-term model-based predictions.

    PubMed

    Theeten, Heidi; Van Herck, Koen; Van Der Meeren, Olivier; Crasta, Priya; Van Damme, Pierre; Hens, Niel

    2015-10-13

    Antibody persistence in two cohorts of adults, who received inactivated hepatitis A (HAV) vaccine (1440El.U; Havrix; GSK Vaccines) according to a 0-6 or 0-12 month schedule in 1992-1993, has been measured annually. After 20 years, >97% of the subjects in both studies were seropositive for anti-HAV antibodies. Geometric mean concentrations in the according-to-protocol cohorts were 312 mIU/ml in 34/36 subjects vaccinated initially at 0-6 months (NCT00289757) and 317 mIU/ml in 85/86 subjects vaccinated at 0-12 months (NCT00291876). Over the whole follow-up period, seven subjects (2+5, respectively) lost circulating anti-HAV antibodies but mounted a strong response after HAV booster administration (1440El.U). Mathematical modelling, which was applied to assess true persistence at Year 20 (accounting for drop-outs and missing data), and to predict longer-term persistence confirmed previous estimates that seropositive anti-HAV levels would persist in ≥95% vaccinees at Year 30 and ≥90% at Year 40. ClinicalTrials.Gov number: NCT00289757/NCT00291876.

  3. Occupational dose constraints in interventional cardiology procedures: the DIMOND approach

    NASA Astrophysics Data System (ADS)

    Tsapaki, Virginia; Kottou, Sophia; Vano, Eliseo; Komppa, Tuomo; Padovani, Renato; Dowling, Annita; Molfetas, Michael; Neofotistou, Vassiliki

    2004-03-01

    Radiation fields involved in angiographic suites are most uneven with intensity and gradient varying widely with projection geometry. The European Commission DIMOND III project addressed among others, the issues regarding optimization of staff doses with an attempt to propose preliminary occupational dose constraints. Two thermoluminescent dosemeters (TLD) were used to assess operators' extremity doses (left shoulder and left foot) during 20 coronary angiographies (CAs) and 20 percutaneous transluminal coronary angioplasties (PTCAs) in five European centres. X-ray equipment, radiation protection measures used and the dose delivered to the patient in terms of dose-area product (DAP) were recorded so as to subsequently associate them with operator's dose. The range of staff doses noted for the same TLD position, centre and procedure type emphasizes the importance of protective measures and technical characteristics of x-ray equipment. Correlation of patient's DAP with staff shoulder dose is moderate whereas correlation of patient's DAP with staff foot dose is poor in both CA and PTCA. Therefore, it is difficult to predict operator's dose from patient's DAP mainly due to the different use of protective measures. A preliminary occupational dose constraint value was defined by calculating cardiologists' annual effective dose and found to be 0.6 mSv.

  4. Dose Reduction Techniques

    SciTech Connect

    WAGGONER, L.O.

    2000-05-16

    As radiation safety specialists, one of the things we are required to do is evaluate tools, equipment, materials and work practices and decide whether the use of these products or work practices will reduce radiation dose or risk to the environment. There is a tendency for many workers that work with radioactive material to accomplish radiological work the same way they have always done it rather than look for new technology or change their work practices. New technology is being developed all the time that can make radiological work easier and result in less radiation dose to the worker or reduce the possibility that contamination will be spread to the environment. As we discuss the various tools and techniques that reduce radiation dose, keep in mind that the radiological controls should be reasonable. We can not always get the dose to zero, so we must try to accomplish the work efficiently and cost-effectively. There are times we may have to accept there is only so much you can do. The goal is to do the smart things that protect the worker but do not hinder him while the task is being accomplished. In addition, we should not demand that large amounts of money be spent for equipment that has marginal value in order to save a few millirem. We have broken the handout into sections that should simplify the presentation. Time, distance, shielding, and source reduction are methods used to reduce dose and are covered in Part I on work execution. We then look at operational considerations, radiological design parameters, and discuss the characteristics of personnel who deal with ALARA. This handout should give you an overview of what it takes to have an effective dose reduction program.

  5. Dose Calculation Spreadsheet

    SciTech Connect

    Simpkins, Ali

    1997-06-10

    VENTSAR XL is an EXCEL Spreadsheet that can be used to calculate downwind doses as a result of a hypothetical atmospheric release. Both building effects and plume rise may be considered. VENTSAR XL will run using any version of Microsoft EXCEL version 4.0 or later. Macros (the programming language of EXCEL) was used to automate the calculations. The user enters a minimal amount of input and the code calculates the resulting concentrations and doses at various downwind distances as specified by the user.

  6. Higher Prescription Opioid Dose is Associated With Worse Patient-Reported Pain Outcomes and More Health Care Utilization.

    PubMed

    Morasco, Benjamin J; Yarborough, Bobbi Jo; Smith, Ning X; Dobscha, Steven K; Deyo, Richard A; Perrin, Nancy A; Green, Carla A

    2017-04-01

    Some previous research has examined pain-related variables on the basis of prescription opioid dose, but data from studies involving patient-reported outcomes have been limited. This study examined the relationships between prescription opioid dose and self-reported pain intensity, function, quality of life, and mental health. Participants were recruited from 2 large integrated health systems, Kaiser Permanente Northwest (n = 331) and VA Portland Health Care System (n = 186). To be included, participants had to have musculoskeletal pain diagnoses and be receiving stable doses of long-term opioid therapy. We divided participants into 3 groups on the basis of current prescription opioid dose in daily morphine equivalent dose (MED): low dose (5-20 mg MED), moderate dose (20.1-50 mg MED), and higher dose (50.1-120 mg MED) groups. A statistically significant trend emerged where higher prescription opioid dose was associated with moderately sized effects including greater pain intensity, more impairments in functioning and quality of life, poorer self-efficacy for managing pain, greater fear avoidance, and more health care utilization. Rates of potential alcohol and substance use disorders also differed among groups. Findings from this evaluation reveal significant differences in pain-related and substance-related factors on the basis of prescription opioid dose.

  7. Dose-Response Calculator for ArcGIS

    USGS Publications Warehouse

    Hanser, Steven E.; Aldridge, Cameron L.; Leu, Matthias; Nielsen, Scott E.

    2011-01-01

    The Dose-Response Calculator for ArcGIS is a tool that extends the Environmental Systems Research Institute (ESRI) ArcGIS 10 Desktop application to aid with the visualization of relationships between two raster GIS datasets. A dose-response curve is a line graph commonly used in medical research to examine the effects of different dosage rates of a drug or chemical (for example, carcinogen) on an outcome of interest (for example, cell mutations) (Russell and others, 1982). Dose-response curves have recently been used in ecological studies to examine the influence of an explanatory dose variable (for example, percentage of habitat cover, distance to disturbance) on a predicted response (for example, survival, probability of occurrence, abundance) (Aldridge and others, 2008). These dose curves have been created by calculating the predicted response value from a statistical model at different levels of the explanatory dose variable while holding values of other explanatory variables constant. Curves (plots) developed using the Dose-Response Calculator overcome the need to hold variables constant by using values extracted from the predicted response surface of a spatially explicit statistical model fit in a GIS, which include the variation of all explanatory variables, to visualize the univariate response to the dose variable. Application of the Dose-Response Calculator can be extended beyond the assessment of statistical model predictions and may be used to visualize the relationship between any two raster GIS datasets (see example in tool instructions). This tool generates tabular data for use in further exploration of dose-response relationships and a graph of the dose-response curve.

  8. Compelling Issues Compounding the Understanding of Low Dose Radiation Effects: But Do They Matter?

    PubMed

    Morgan, William F

    2016-03-01

    Recent advances in low dose radiation research have raised a number of compelling issues that have compounded the understanding of low dose radiation effects. Here some of them are outlined: the linear no-threshold model for predicting effects at low radiation doses, dose rate effectiveness factor, attributability, and public perception of low dose radiation effects. The impact of changes in any of these hotly debated issues on radiation protection is considered.

  9. When is a dose not a dose

    SciTech Connect

    Bond, V.P.

    1991-01-01

    Although an enormous amount of progress has been made in the fields of radiation protection and risk assessment, a number of significant problems remain. The one problem which transcends all the rest, and which has been subject to considerable misunderstanding, involves what has come to be known as the 'linear non-threshold hypothesis', or 'linear hypothesis'. Particularly troublesome has been the interpretation that any amount of radiation can cause an increase in the excess incidence of cancer. The linear hypothesis has dominated radiation protection philosophy for more than three decades, with enormous financial, societal and political impacts and has engendered an almost morbid fear of low-level exposure to ionizing radiation in large segments of the population. This document presents a different interpretation of the linear hypothesis. The basis for this view lies in the evolution of dose-response functions, particularly with respect to their use initially in the context of early acute effects, and then for the late effects, carcinogenesis and mutagenesis. 11 refs., 4 figs. (MHB)

  10. Altered interphase fluorescence in situ hybridization profiles of chromosomes 4, 8q24, and 9q34 in pancreatic ductal adenocarcinoma are associated with a poorer patient outcome.

    PubMed

    Gutiérrez, María L; Muñoz-Bellvis, Luis; Sarasquete, María E; Hernández-Mejía, David G; Abad, María del Mar; Bengoechea, Oscar; Corchete, Luis; González-González, María; García-García, Jacinto; Gonzalez, Marcos; Mota, Ines; Orfao, Alberto; Sayagues, José M

    2014-11-01

    Most patients with pancreatic ductal adenocarcinoma (PDAC) die within 6 months of diagnosis. However, 20% to 25% patients undergoing total tumor resection remain alive and disease-free 5 years after diagnostic surgery. Few studies on tumor markers have predicted patient prognosis and/or survival. We evaluated the effect of tumor cytogenetic copy number changes detected by interphase fluorescence in situ hybridization on overall survival (OS) of 55 PDAC patients. The prognostic value of copy number changes showing an effect on OS was validated in an external cohort of 44 surgically resected PDAC patients by comparative genomic hybridization arrays, and the genes coded in altered chromosomes with prognostic value were identified by high-density single-nucleotide polymorphism arrays in 20 cases. Copy number changes of chromosomes 4 and 9q34 with gains of 8q24 were independently associated with shorter OS. On the basis of these three chromosomal alterations, a score is proposed that identifies patients with significantly different (P < 0.001) 5-year OS rates: 60% ± 20%, 16% ± 8%, and 0% ± 0%, respectively. Our results show an association between tumor cytogenetics and OS of PDAC patients and provide the basis for further prognostic stratification of patients undergoing complete tumor resection. Further studies to identify specific genes coded in these chromosomes and their functional consequences are necessary to understand the clinical effect of these changes.

  11. The rich get richer and the poor get poorer: Country- and state-level income inequality moderates the job insecurity-burnout relationship.

    PubMed

    Jiang, Lixin; Probst, Tahira M

    2017-04-01

    Despite the prevalence of income inequality in today's society, research on the implications of income inequality for organizational research is scant. This study takes the first step to explore the contextual role of national- and state- level income inequality as a moderator in the relationship between individual-level job insecurity (JI) and burnout. Drawing from conservation of resource (COR) theory, we argue that income inequality at the country-level and state-level threatens one's obtainment of object (i.e., material coping) and condition (i.e., nonmaterial coping) resources, thus serving as an environmental stressor exacerbating one's burnout reactions to JI. The predicted cross-level interaction effect of income inequality was tested in 2 studies. Study 1 consisting of 23,778 individuals nested in 30 countries explored the moderating effect of country-level income inequality on the relationship between individual JI and exhaustion. Study 2 collected data from 402 employees residing in 48 states in the United States, and tested the moderating effect of state-level income inequality on the relationship between JI and burnout (i.e., emotional exhaustion and cynicism). Results of both studies converge to support the exacerbating role of higher-level income inequality on the JI -burnout relationship. Our findings contribute to the literature on psychological health disparities by exploring the contextual role of income inequality as a predictor of differential reactions to JI. (PsycINFO Database Record

  12. Low-Dose Carcinogenicity Studies

    EPA Science Inventory

    One of the major deficiencies of cancer risk assessments is the lack of low-dose carcinogenicity data. Most assessments require extrapolation from high to low doses, which is subject to various uncertainties. Only 4 low-dose carcinogenicity studies and 5 low-dose biomarker/pre-n...

  13. Measuring pacemaker dose: A clinical perspective

    SciTech Connect

    Studenski, Matthew T.; Xiao Ying; Harrison, Amy S.

    2012-07-01

    Recently in our clinic, we have seen an increased number of patients presenting with pacemakers and defibrillators. Precautions are taken to develop a treatment plan that minimizes the dose to the pacemaker because of the adverse effects of radiation on the electronics. Here we analyze different dosimeters to determine which is the most accurate in measuring pacemaker or defibrillator dose while at the same time not requiring a significant investment in time to maintain an efficient workflow in the clinic. The dosimeters analyzed here were ion chambers, diodes, metal-oxide-semiconductor field effect transistor (MOSFETs), and optically stimulated luminescence (OSL) dosimeters. A simple phantom was used to quantify the angular and energy dependence of each dosimeter. Next, 8 patients plans were delivered to a Rando phantom with all the dosimeters located where the pacemaker would be, and the measurements were compared with the predicted dose. A cone beam computed tomography (CBCT) image was obtained to determine the dosimeter response in the kilovoltage energy range. In terms of the angular and energy dependence of the dosimeters, the ion chamber and diode were the most stable. For the clinical cases, all the dosimeters match relatively well with the predicted dose, although the ideal dosimeter to use is case dependent. The dosimeters, especially the MOSFETS, tend to be less accurate for the plans, with many lateral beams. Because of their efficiency, we recommend using a MOSFET or a diode to measure the dose. If a discrepancy is observed between the measured and expected dose (especially when the pacemaker to field edge is <10 cm), we recommend analyzing the treatment plan to see whether there are many lateral beams. Follow-up with another dosimeter rather than repeating multiple times with the same type of dosimeter. All dosimeters should be placed after the CBCT has been acquired.

  14. Biallelic losses of 13q do not confer a poorer outcome in chronic lymphocytic leukaemia: analysis of 627 patients with isolated 13q deletion.

    PubMed

    Puiggros, Anna; Delgado, Julio; Rodriguez-Vicente, Ana; Collado, Rosa; Aventín, Anna; Luño, Elisa; Grau, Javier; Hernandez, José Ángel; Marugán, Isabel; Ardanaz, Maite; González, Teresa; Valiente, Alberto; Osma, Mar; Calasanz, Maria José; Sanzo, Carmen; Carrió, Ana; Ortega, Margarita; Santacruz, Rodrigo; Abrisqueta, Pau; Abella, Eugènia; Bosch, Francesc; Carbonell, Félix; Solé, Francesc; Hernández, Jesús Maria; Espinet, Blanca

    2013-10-01

    Losses in 13q as a sole abnormality confer a good prognosis in chronic lymphocytic leukaemia (CLL). Nevertheless, its heterogeneity has been demonstrated and the clinical significance of biallelic 13q deletions remains controversial. We compared the clinico-biological characteristics of a series of 627 patients harbouring isolated 13q deletions by fluorescence in situ hybridization (FISH), either monoallelic (13q × 1), biallelic (13q × 2), or the coexistence of both clones (13qM). The most frequent 13q deletion was 13q × 1 (82·1%), while 13q × 2 and 13qM represented 8·6% and 9·3% of patients respectively. The median percentage of altered nuclei significantly differed across groups: 55%, 72·5% and 80% in 13q × 1, 13q × 2 and 13qM (P < 0·001). However, no significant differences in the clinical outcome among 13q groups were found. From 84 patients with sequential FISH studies, eight patients lost the remaining allele of 13q whereas none of them changed from 13q × 2 to the 13q × 1 group. The percentage of abnormal cells detected by FISH had a significant impact on the five-year cumulative incidence of treatment and the overall survival, 90% being the highest predictive power cut-off. In conclusion, loss of the remaining 13q allele is not enough to entail a worse prognosis in CLL. The presence of isolated 13q deletion can be risk-stratified according to the percentage of altered cells.

  15. EEG Abnormalities Are Associated With Poorer Depressive Symptom Outcomes With Escitalopram and Venlafaxine-XR, but Not Sertraline: Results From the Multicenter Randomized iSPOT-D Study.

    PubMed

    Arns, Martijn; Gordon, Evian; Boutros, Nash N

    2017-01-01

    Rationale Limited research is available on electrophysiological abnormalities such as epileptiform EEG or EEG slowing in depression and its association with antidepressant treatment response. Objectives We investigated the association between EEG abnormalities and antidepressant treatment response in the international Study to Predict Optimized Treatment in Depression (iSPOT-D). Methods Of 1008 participants with major depressive disorder randomized to escitalopram, sertraline, or venlafaxine-XR, 622 completed 8 weeks of treatment per protocol. The study also recruited 336 healthy controls. Treatment response was established after 8 weeks using the 17-item Hamilton Rating Scale for Depression (HRSD17). The resting-state EEG was assessed at baseline with eyes closed. EEG abnormalities including epileptiform activity, EEG slowing, and alpha peak frequency (APF) were scored for all subjects, blind to treatment outcome. Results Patients and controls did not differ in the occurrence of EEG abnormalities. Furthermore, in the per protocol sample the occurrence of epileptiform EEG and EEG slowing (as a combined marker) were associated with a reduced likelihood of responding to escitalopram (P = .019; odds ratio [OR] = 3.56) and venlafaxine-XR (P = .043; OR = 2.76), but not sertraline (OR = 0.73). The response rates for this "any EEG abnormality" groups versus the "no-abnormality" group were 33% and 64% for escitalopram and 41% and 66% for venlafaxine-XR, respectively. A slow APF was associated with treatment response only in the sertraline group (P = .21; d = .027). Conclusions EEG abnormalities are associated with nonresponse to escitalopram and venlafaxine-XR, but not sertraline, whereas a slow APF is associated to response for sertraline only.

  16. NOTE: Validation of blood product irradiation doses

    NASA Astrophysics Data System (ADS)

    Cheung, T.; Butson, M.; Yu, P. K. N.

    2001-10-01

    Dosimetry of blood irradiation using x-ray beams on a medical linear accelerator has been studied to evaluate the accuracy of a diode detector and the delivery achievable. Variations in applied doses for a standard dual field 6 MV x-ray are measured with a commercial diode detector. Results show that the diode detector measured applied in vitro doses to within 5.4% (2 standard deviations (2 SD)) of those calculated with a collapsed-cone convolution treatment-planning computer for a sample of 100 blood irradiations. Experiments involving the packing procedure of the blood products in the blood box were performed. It was found that a large proportion of the variation in the predicted and measured dose was due to the compacting of the scatter material at the base of the blood box (over a 6 month period) producing a higher density below the blood than originally scanned; hence an overall reduction of delivered dose was observed. The diode measurements (which provide an immediate printout) are recommended in conjunction with a film dosimeter such as radiochromic film, which still provides a back-up dose monitor and a visual reminder that the blood has been irradiated. It is also recommended that the blood box be completely evacuated of all scatter material every month and the base be carefully repacked to provide uniform scatter material.

  17. Validation of blood product irradiation doses.

    PubMed

    Cheung, T; Butson, M; Yu, P K

    2001-10-01

    Dosimetry of blood irradiation using x-ray beams on a medical linear accelerator has been studied to evaluate the accuracy of a diode detector and the delivery achievable. Variations in applied doses for a standard dual field 6 MV x-ray are measured with a commercial diode detector. Results show that the diode detector measured applied in vitro doses to within 5.4% (2 standard deviations (2 SD)) of those calculated with a collapsed-cone convolution treatment-planning computer for a sample of 100 blood irradiations. Experiments involving the packing procedure of the blood products in the blood box were performed. It was found that a large proportion of the variation in the predicted and measured dose was due to the compacting of the scatter material at the base of the blood box (over a 6 month period) producing a higher density below the blood than originally scanned; hence an overall reduction of delivered dose was observed. The diode measurements (which provide an immediate printout) are recommended in conjunction with a film dosimeter such as radiochromic film, which still provides a back-up dose monitor and a visual reminder that the blood has been irradiated. It is also recommended that the blood box be completely evacuated of all scatter material every month and the base be carefully repacked to provide uniform scatter material.

  18. Individual external dose monitoring of all citizens of Date City by passive dosimeter 5 to 51 months after the Fukushima NPP accident (series): 1. Comparison of individual dose with ambient dose rate monitored by aircraft surveys.

    PubMed

    Miyazaki, Makoto; Hayano, Ryugo

    2016-12-06

    Date (da'te) City in Fukushima Prefecture has conducted a population-wide individual dose monitoring program after the Fukushima Daiichi Nuclear Power Plant Accident, which provides a unique and comprehensive data set of the individual doses of citizens. The purpose of this paper, the first in the series, is to establish a method for estimating effective doses based on the available ambient dose rate survey data. We thus examined the relationship between the individual external doses and the corresponding ambient doses assessed from airborne surveys. The results show that the individual doses were about 0.15 times the ambient doses, the coefficient of 0.15 being a factor of 4 smaller than the value employed by the Japanese government, throughout the period of the airborne surveys used. The method obtained in this study could aid in the prediction of individual doses in the early phase of future radiological accidents involving large-scale contamination.

  19. Comparative serum bactericidal activities of three doses of ciprofloxacin administered intravenously.

    PubMed Central

    Dan, M; Poch, F; Quassem, C; Kitzes, R

    1994-01-01

    The pharmacokinetics and serum bactericidal activities of three intravenous doses of ciprofloxacin were studied comparatively in 30 patients. Single 200-, 300-, and 400-mg intravenous doses of ciprofloxacin were given over 30 min to 10 patients each, and serum samples were obtained at 0.5, 1, 2, 3, 4, 8, and 12 h after the start of the infusion. Serum drug concentrations were determined by high-pressure liquid chromatography. Pharmacokinetic parameters were estimated by using noncompartmental analysis methods. Serum bactericidal activity against clinical isolates of Escherichia coli, Enterobacter cloacae, Pseudomonas aeruginosa, Acinetobacter calcoaceticus, and Staphylococcus aureus was determined for samples obtained at 0.5, 4, 8, and 12 h. Excellent activity was demonstrated up to 12 h by all doses against E. coli and E. cloacae. Much poorer titers were observed for the remaining organisms, although the 400-mg dose prompted improved results against P. aeruginosa with a mean bactericidal titer of 1:2.9 at 8 h. In conclusion, while the 200-mg dose appears to be largely adequate for infections caused by members of the family Enterobacteriaceae, it seems that when P. aeruginosa is involved, 400 mg twice a day or even three times a day is more appropriate. Intravenous ciprofloxacin performs poorly against A. calcoaceticus and S. aureus, even at a higher dose. PMID:8031055

  20. Absorbed dose from traversing spherically symmetric, Gaussian radioactive clouds

    SciTech Connect

    Thompson, J.M. ); Poston, J.W. . Dept. of Nuclear Engineering)

    1999-06-01

    If a large radioactive cloud is produced, sampling may require that an airplane traverse the cloud. A method to predict the absorbed dose to the aircrew from penetrating the radioactive cloud is needed. Dose rates throughout spherically symmetric Gaussian clouds of various sizes, and the absorbed doses from traversing the clouds, were calculated. Cloud size is a dominant parameter causing dose to vary by orders of magnitude for a given dose rate measured at some distance. A method to determine cloud size, based on dose rate readings at two or more distances from the cloud center, was developed. This method, however, failed to resolve the smallest cloud sizes from measurements made at 1,000 m to 2,000 m from the cloud center.

  1. Radiotherapy Dose-Volume Effects on Salivary Gland Function

    SciTech Connect

    Deasy, Joseph O.; Moiseenko, Vitali; Marks, Lawrence; Chao, K.S. Clifford; Nam, Jiho; Eisbruch, Avraham

    2010-03-01

    Publications relating parotid dose-volume characteristics to radiotherapy-induced salivary toxicity were reviewed. Late salivary dysfunction has been correlated to the mean parotid gland dose, with recovery occurring with time. Severe xerostomia (defined as long-term salivary function of <25% of baseline) is usually avoided if at least one parotid gland is spared to a mean dose of less than {approx}20 Gy or if both glands are spared to less than {approx}25 Gy (mean dose). For complex, partial-volume RT patterns (e.g., intensity-modulated radiotherapy), each parotid mean dose should be kept as low as possible, consistent with the desired clinical target volume coverage. A lower parotid mean dose usually results in better function. Submandibular gland sparing also significantly decreases the risk of xerostomia. The currently available predictive models are imprecise, and additional study is required to identify more accurate models of xerostomia risk.

  2. Estimation of the Dose and Dose Rate Effectiveness Factor

    NASA Technical Reports Server (NTRS)

    Chappell, L.; Cucinotta, F. A.

    2013-01-01

    Current models to estimate radiation risk use the Life Span Study (LSS) cohort that received high doses and high dose rates of radiation. Transferring risks from these high dose rates to the low doses and dose rates received by astronauts in space is a source of uncertainty in our risk calculations. The solid cancer models recommended by BEIR VII [1], UNSCEAR [2], and Preston et al [3] is fitted adequately by a linear dose response model, which implies that low doses and dose rates would be estimated the same as high doses and dose rates. However animal and cell experiments imply there should be curvature in the dose response curve for tumor induction. Furthermore animal experiments that directly compare acute to chronic exposures show lower increases in tumor induction than acute exposures. A dose and dose rate effectiveness factor (DDREF) has been estimated and applied to transfer risks from the high doses and dose rates of the LSS cohort to low doses and dose rates such as from missions in space. The BEIR VII committee [1] combined DDREF estimates using the LSS cohort and animal experiments using Bayesian methods for their recommendation for a DDREF value of 1.5 with uncertainty. We reexamined the animal data considered by BEIR VII and included more animal data and human chromosome aberration data to improve the estimate for DDREF. Several experiments chosen by BEIR VII were deemed inappropriate for application to human risk models of solid cancer risk. Animal tumor experiments performed by Ullrich et al [4], Alpen et al [5], and Grahn et al [6] were analyzed to estimate the DDREF. Human chromosome aberration experiments performed on a sample of astronauts within NASA were also available to estimate the DDREF. The LSS cohort results reported by BEIR VII were combined with the new radiobiology results using Bayesian methods.

  3. Dose esclation in radioimmunotherapy based on projected whole body dose

    SciTech Connect

    Wahl, R.L.; Kaminski, M.S.; Regan, D.

    1994-05-01

    A variety of approaches have been utilized in conducting phase I radioimmunotherapy dose-escalation trials. Escalation of dose has been based on graded increases in administered mCi; mCi/kg; or mCi/m2. It is also possible to escalate dose based on tracer-projected marrow, blood or whole body radiation dose. We describe our results in performing a dose-escalation trial in patients with non-Hodgkin lymphoma based on escalating administered whole-body radiation dose. The mCi dose administered was based on a patient-individualized tracer projected whole-body dose. 25 patients were entered on the study. RIT with 131 I anti-B-1 was administered to 19 patients. The administered dose was prescribed based on the projected whole body dose, determined from patient-individualized tracer studies performed prior to RIT. Whole body dose estimates were based on the assumption that the patient was an ellipsoid, with 131 antibody kinetics determined using a whole-body probe device acquiring daily conjugate views of 1 minute duration/view. Dose escalation levels proceeded with 10 cGy increments from 25 cGy whole-body and continues, now at 75 cGy. The correlation among potential methods of dose escalation and toxicity was assessed. Whole body radiation dose by probe was strongly correlated with the blood radiation dose determined from sequential blood sampling during tracer studies (r=.87). Blood radiation dose was very weakly correlated with mCi dose (r=.4) and mCi/kg (r=.45). Whole body radiation dose appeared less well-correlated with injected dose in mCi (r=.6), or mCi/kg (r=.64). Toxicity has been infrequent in these patients, but appears related to increasing whole body dose. Non-invasive determination of whole-body radiation dose by gamma probe represents a non-invasive method of estimating blood radiation dose, and thus of estimating bone marrow radiation dose.

  4. A Four-Step and Four-Criteria Approach for Evaluating Evidence of Dose Addition in Chemical Mixture Toxicity

    EPA Science Inventory

    Dose addition is the most frequently-used component-based approach for predicting dose response for a mixture of toxicologically-similar chemicals and for statistical evaluation of whether the mixture response is consistent with dose additivity and therefore predictable from the ...

  5. Climate prediction and predictability

    NASA Astrophysics Data System (ADS)

    Allen, Myles

    2010-05-01

    Climate prediction is generally accepted to be one of the grand challenges of the Geophysical Sciences. What is less widely acknowledged is that fundamental issues have yet to be resolved concerning the nature of the challenge, even after decades of research in this area. How do we verify or falsify a probabilistic forecast of a singular event such as anthropogenic warming over the 21st century? How do we determine the information content of a climate forecast? What does it mean for a modelling system to be "good enough" to forecast a particular variable? How will we know when models and forecasting systems are "good enough" to provide detailed forecasts of weather at specific locations or, for example, the risks associated with global geo-engineering schemes. This talk will provide an overview of these questions in the light of recent developments in multi-decade climate forecasting, drawing on concepts from information theory, machine learning and statistics. I will draw extensively but not exclusively from the experience of the climateprediction.net project, running multiple versions of climate models on personal computers.

  6. Rates of Change in Naturalistic Psychotherapy: Contrasting Dose-Effect and Good-Enough Level Models of Change

    ERIC Educational Resources Information Center

    Baldwin, Scott A.; Berkeljon, Arjan; Atkins, David C.; Olsen, Joseph A.; Nielsen, Stevan L.

    2009-01-01

    Most research on the dose-effect model of change has combined data across patients who vary in their total dose of treatment and has implicitly assumed that the rate of change during therapy is constant across doses. In contrast, the good-enough level model predicts that rate of change will be related to total dose of therapy. In this study, the…

  7. Commentary 2 to Cox and Little: radiation-induced oncogenic transformation: the interplay between dose, dose protraction, and radiation quality

    NASA Technical Reports Server (NTRS)

    Brenner, D. J.; Hall, E. J.

    1992-01-01

    There is now a substantial body of evidence for end points such as oncogenic transformation in vitro, and carcinogenesis and life shortening in vivo, suggesting that dose protraction leads to an increase in effectiveness relative to a single, acute exposure--at least for radiations of medium linear energy transfer (LET) such as neutrons. Table I contains a summary of the pertinent data from studies in which the effect is seen. [table: see text] This phenomenon has come to be known as the "inverse dose rate effect," because it is in marked contrast to the situation at low LET, where protraction in delivery of a dose of radiation, either by fractionation or low dose rate, results in a decreased biological effect; additionally, at medium and high LET, for radiobiological end points such as clonogenic survival, the biological effectiveness is independent of protraction. The quantity and quality of the published reports on the "inverse dose rate effect" leaves little doubt that the effect is real, but the available evidence indicates that the magnitude of the effect is due to a complex interplay between dose, dose rate, and radiation quality. Here, we first summarize the available data on the inverse dose rate effect and suggest that it follows a consistent pattern in regard to dose, dose rate, and radiation quality; second, we describe a model that predicts these features; and, finally, we describe the significance of the effect for radiation protection.

  8. Hanford Environmental Dose Reconstruction Project

    SciTech Connect

    Finch, S.M.; McMakin, A.H.

    1992-01-01

    The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed, from release to impact on humans (dose estimates): Source Terms, Environmental Transport, Environmental Monitoring Data, Demography, Food Consumption, and Agriculture, and Environmental Pathways and Dose Estimates.

  9. Hanford Environmental Dose Reconstruction Project

    SciTech Connect

    Finch, S.M.; McMakin, A.H.

    1991-01-01

    The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed, from release to impact on humans (dose estimates): Source terms; environmental transport environmental monitoring data; demographics, agriculture, food habits; environmental pathways and dose estimates.

  10. Hanford Environmental Dose Reconstruction Project

    SciTech Connect

    Finch, S.M.; McMakin, A.H.

    1992-02-01

    The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed, from release to impact on humans (dose estimates): source terms; environmental transport; environmental monitoring data; demography, food consumption, and agriculture; environmental pathways and dose estimates.

  11. Hanford Environmental Dose Reconstruction Project

    SciTech Connect

    Cannon, S.D.; Finch, S.M.

    1992-10-01

    The objective of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The independent Technical Steering Panel (TSP) provides technical direction. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed from release to impact on humans (dose estimates):Source Terms, Environmental Transport, Environmental Monitoring Data, Demography, Food Consumption, and Agriculture, and Environmental Pathways and Dose Estimates.

  12. Radiation damage in single-particle cryo-electron microscopy: effects of dose and dose rate

    PubMed Central

    Karuppasamy, Manikandan; Karimi Nejadasl, Fatemeh; Vulovic, Milos; Koster, Abraham J.; Ravelli, Raimond B. G.

    2011-01-01

    Radiation damage is an important resolution limiting factor both in macromolecular X-ray crystallography and cryo-electron microscopy. Systematic studies in macromolecular X-ray crystallography greatly benefited from the use of dose, expressed as energy deposited per mass unit, which is derived from parameters including incident flux, beam energy, beam size, sample composition and sample size. In here, the use of dose is reintroduced for electron microscopy, accounting for the electron energy, incident flux and measured sample thickness and composition. Knowledge of the amount of energy deposited allowed us to compare doses with experimental limits in macromolecular X-ray crystallography, to obtain an upper estimate of radical concentrations that build up in the vitreous sample, and to translate heat-transfer simulations carried out for macromolecular X-ray crystallography to cryo-electron microscopy. Stroboscopic exposure series of 50–250 images were collected for different incident flux densities and integration times from Lumbricus terrestris extracellular hemoglobin. The images within each series were computationally aligned and analyzed with similarity metrics such as Fourier ring correlation, Fourier ring phase residual and figure of merit. Prior to gas bubble formation, the images become linearly brighter with dose, at a rate of approximately 0.1% per 10 MGy. The gradual decomposition of a vitrified hemoglobin sample could be visualized at a series of doses up to 5500 MGy, by which dose the sample was sublimed. Comparison of equal-dose series collected with different incident flux densities showed a dose-rate effect favoring lower flux densities. Heat simulations predict that sample heating will only become an issue for very large dose rates (50 e−Å−2 s−1 or higher) combined with poor thermal contact between the grid and cryo-holder. Secondary radiolytic effects are likely to play a role in dose-rate effects. Stroboscopic data collection

  13. Increased mRNA Levels of Sphingosine Kinases and S1P Lyase and Reduced Levels of S1P Were Observed in Hepatocellular Carcinoma in Association with Poorer Differentiation and Earlier Recurrence.

    PubMed

    Uranbileg, Baasanjav; Ikeda, Hitoshi; Kurano, Makoto; Enooku, Kenichiro; Sato, Masaya; Saigusa, Daisuke; Aoki, Junken; Ishizawa, Takeaki; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

    2016-01-01

    Although sphingosine 1-phosphate (S1P) has been reported to play an important role in cancer pathophysiology, little is known about S1P and hepatocellular carcinoma (HCC). To clarify the relationship between S1P and HCC, 77 patients with HCC who underwent surgical treatment were consecutively enrolled in this study. In addition, S1P and its metabolites were quantitated by LC-MS/MS. The mRNA levels of sphingosine kinases (SKs), which phosphorylate sphingosine to generate S1P, were increased in HCC tissues compared with adjacent non-HCC tissues. Higher mRNA levels of SKs in HCC were associated with poorer differentiation and microvascular invasion, whereas a higher level of SK2 mRNA was a risk factor for intra- and extra-hepatic recurrence. S1P levels, however, were unexpectedly reduced in HCC compared with non-HCC tissues, and increased mRNA levels of S1P lyase (SPL), which degrades S1P, were observed in HCC compared with non-HCC tissues. Higher SPL mRNA levels in HCC were associated with poorer differentiation. Finally, in HCC cell lines, inhibition of the expression of SKs or SPL by siRNA led to reduced proliferation, invasion and migration, whereas overexpression of SKs or SPL enhanced proliferation. In conclusion, increased SK and SPL mRNA expression along with reduced S1P levels were more commonly observed in HCC tissues compared with adjacent non-HCC tissues and were associated with poor differentiation and early recurrence. SPL as well as SKs may be therapeutic targets for HCC treatment.

  14. The relative biological effectiveness of out-of-field dose

    NASA Astrophysics Data System (ADS)

    Balderson, Michael; Koger, Brandon; Kirkby, Charles

    2016-01-01

    Purpose: using simulations and models derived from existing literature, this work investigates relative biological effectiveness (RBE) for out-of-field radiation and attempts to quantify the relative magnitudes of different contributing phenomena (spectral, bystander, and low dose hypersensitivity effects). Specific attention is paid to external beam radiotherapy treatments for prostate cancer. Materials and methods: using different biological models that account for spectral, bystander, and low dose hypersensitivity effects, the RBE was calculated for different points moving radially out from isocentre for a typical single arc VMAT prostate case. The RBE was found by taking the ratio of the equivalent dose with the physical dose. Equivalent doses were calculated by determining what physical dose would be necessary to produce the same overall biological effect as that predicted using the different biological models. Results: spectral effects changed the RBE out-of-field less than 2%, whereas response models incorporating low dose hypersensitivity and bystander effects resulted in a much more profound change of the RBE for out-of-field doses. The bystander effect had the largest RBE for points located just outside the edge of the primary radiation beam in the cranial caudal (z-direction) compared to low dose hypersensitivity and spectral effects. In the coplanar direction, bystander effect played the largest role in enhancing the RBE for points up to 8.75 cm from isocentre. Conclusions: spectral, bystander, and low dose hypersensitivity effects can all increase the RBE for out-of-field radiation doses. In most cases, bystander effects seem to play the largest role followed by low dose hypersensitivity. Spectral effects were unlikely to be of any clinical significance. Bystander, low dose hypersensitivity, and spectral effect increased the RBE much more in the cranial caudal direction (z-direction) compared with the coplanar directions.

  15. Optimization of temporal dose modulation: Comparison of theory and experiment

    SciTech Connect

    Bewes, J. M.; Suchowerska, N.; Cartwright, L.; Ebert, M. A.; McKenzie, D. R.

    2012-06-15

    Purpose: To compare theoretical predictions and experimental measurements of cell survival after exposure to two different temporally modulated radiation dose patterns that deliver the same dose in the same overall time. Methods: The authors derived an analytic expression for the dose protraction factor G in the Lea-Catcheside formalism for cell survival for 'triangle' and 'V' temporal modulation of dose. These temporal dose patterns were used in experimental clonogenic studies of a melanoma cell line (MM576) and a nonsmall-cell lung cancer line (NCI-H460) that have different alpha, beta, and repair parameters. The overall treatment time and total dose were kept constant. Results: The analytic expressions for G for the two temporal modulations are presented as a function of a single variable, the product of the exposure time, and the repair constant, enabling G to be evaluated for any exposure time and for any cell line. G for the triangle delivery pattern is always the larger. For the MM576 cell line, following a large dose of 6 Gy, a larger survival fraction was found for the V delivery pattern. No difference in survival was observed for lower doses or for the NCI-H460 cell line at any dose. These results are predicted by our theory, using published values of alpha, beta, and repair time within the limits of experimental uncertainty. Conclusions: The study provides evidence to confirm that cell lines having large beta values exhibit a response that is sensitive to the pattern of dose delivery when the delivery time is comparable with the repair time. It is recommended that the dose delivery pattern be considered in hypofractionated treatments.

  16. The relationship between neuroleptic drug dose and the performance of psychiatric patients in a maximum security token economy program.

    PubMed

    Harris, G T

    1989-03-01

    This study examined the relationship between neuroleptic medication dose and performance in a token economy program on two maximum security psychiatric wards. Patients receiving higher than average doses exhibited poorer than average program performance but there was a small but statistically significant positive relationship between neuroleptic drug dose (measured in CPZ units/kg) and program performance. However, this positive relationship existed only for the first few weeks of patients' hospital stays, and there was a delay (approximately 2 weeks) between the administration of the drug and the maximal positive effect on program performance. Only a very small minority of medication changes were ever followed by improvements in program performance. The results are discussed in terms of what is a rational strategy for the provision of psychiatric medication and other forms of treatment in institutional settings.

  17. Comparison of organ dose and dose equivalent for human phantoms of CAM vs. MAX

    NASA Astrophysics Data System (ADS)

    Kim, Myung-Hee Y.; Qualls, Garry D.; Slaba, Tony C.; Cucinotta, Francis A.

    2010-04-01

    For the evaluation of organ dose and dose equivalent of astronauts on space shuttle and the International Space Station (ISS) missions, the CAMERA models of CAM (Computerized Anatomical Male) and CAF (Computerized Anatomical Female) of human tissue shielding have been implemented and used in radiation transport model calculations at NASA. One of new human geometry models to meet the “reference person” of International Commission on Radiological Protection (ICRP) is based on detailed Voxel (volumetric and pixel) phantom models denoted for male and female as MAX (Male Adult voXel) and FAX (Female Adult voXel), respectively. We compared the CAM model predictions of organ doses to those of MAX model, since the MAX model represents the male adult body with much higher fidelity than the CAM model currently used at NASA. Directional body-shielding mass was evaluated for over 1500 target points of MAX for specified organs considered to be sensitive to the induction of stochastic effects. Radiation exposures to solar particle event (SPE), trapped protons, and galactic cosmic ray (GCR) were assessed at the specific sites in the MAX phantom by coupling space radiation transport models with the relevant body-shielding mass. The development of multiple-point body-shielding distributions at each organ made it possible to estimate the mean and variance of organ doses at the specific organ. For the estimate of doses to the blood forming organs (BFOs), data on active marrow distributions in adult were used to weight the bone marrow sites over the human body. The discrete number of target points of MAX organs resulted in a reduced organ dose and dose equivalent compared to the results of CAM organs especially for SPE, and should be further investigated. Differences of effective doses between the two approaches were found to be small (<5%) for GCR.

  18. The importance of carcinogen dose in chemoprevention studies: quantitative interrelationships between, dibenzo[a,l]pyrene dose, chlorophyllin dose, target organ DNA adduct biomarkers and final tumor outcome.

    PubMed

    Pratt, M Margaret; Reddy, Ashok P; Hendricks, Jerry D; Pereira, Cliff; Kensler, Thomas W; Bailey, George S

    2007-03-01

    Chlorophyllin (CHL) is a potent antimutagen in vitro, an effective anti-carcinogen in several animal models, and significantly reduced urinary biomarkers of aflatoxin B(1) (AFB(1)) exposure in a human population. Here we report an expanded analysis of CHL chemoprevention using the potent environmental hydrocarbon dibenzo[a,l]pyrene (DBP). A dose-dose matrix design employed over 12 000 rainbow trout to evaluate the interrelationships among dietary carcinogen dose, anti-carcinogen dose, carcinogen-DNA adduct levels at exposure and eventual tumor outcome in two target organs. Included was an evaluation of the pharmaceutical CHL preparation (Derifil), used previously in a study of individuals chronically exposed to AFB(1). CHL was pre-, co- and post-fed at doses of 0-6000 p.p.m. and co-fed with DBP at doses of 0-371.5 p.p.m. for 4 weeks. This protocol generated a total of 21 dose-dose treatment groups, each evaluated with three or more replicates of 100 animals. The DBP-only treatment produced dose-responsive increases in liver and stomach DBP-DNA adducts, whereas increasing CHL co-treatment doses produced successive inhibition in liver (49-83%) and stomach (47-75%) adduct levels at each DBP dose examined. The remaining 8711 trout were necropsied, 10 months later. DBP treatment alone produced a logit incidence versus log [DBP] dose-response curve in stomach that was linear; CHL co-treatment provided dose-dependent tumor inhibition which ranged from 30 to 68% and was predictable from the adduct response. The Derifil CHL preparation was also found to effectively reduce DNA adduction and final tumor incidence in stomach (as well as liver), with a potency compatible with its total chlorin content. Liver tumor incidence in the DBP-only groups appeared to plateau near 60%. At DBP doses of doses generally reduced tumor incidence and multiplicity consistent with early DNA adducts as biomarkers. At 225 p.p.m. DBP, however, very high CHL doses were

  19. Survey of computed tomography scanners in Taiwan: Dose descriptors, dose guidance levels, and effective doses

    SciTech Connect

    Tsai, H. Y.; Tung, C. J.; Yu, C. C.; Tyan, Y. S.

    2007-04-15

    The IAEA and the ICRP recommended dose guidance levels for the most frequent computed tomography (CT) examinations to promote strategies for the optimization of radiation dose to CT patients. A national survey, including on-site measurements and questionnaires, was conducted in Taiwan in order to establish dose guidance levels and evaluate effective doses for CT. The beam quality and output and the phantom doses were measured for nine representative CT scanners. Questionnaire forms were completed by respondents from facilities of 146 CT scanners out of 285 total scanners. Information on patient, procedure, scanner, and technique for the head and body examinations was provided. The weighted computed tomography dose index (CTDI{sub w}), the dose length product (DLP), organ doses and effective dose were calculated using measured data, questionnaire information and Monte Carlo simulation results. A cost-effective analysis was applied to derive the dose guidance levels on CTDI{sub w} and DLP for several CT examinations. The mean effective dose{+-}standard deviation distributes from 1.6{+-}0.9 mSv for the routine head examination to 13{+-}11 mSv for the examination of liver, spleen, and pancreas. The surveyed results and the dose guidance levels were provided to the national authorities to develop quality control standards and protocols for CT examinations.

  20. Earthquake prediction

    NASA Technical Reports Server (NTRS)

    Turcotte, Donald L.

    1991-01-01

    The state of the art in earthquake prediction is discussed. Short-term prediction based on seismic precursors, changes in the ratio of compressional velocity to shear velocity, tilt and strain precursors, electromagnetic precursors, hydrologic phenomena, chemical monitors, and animal behavior is examined. Seismic hazard assessment is addressed, and the applications of dynamical systems to earthquake prediction are discussed.

  1. The Audacity of Hope: Towards Poorer Pedagogies

    ERIC Educational Resources Information Center

    Fenwick, Tara

    2006-01-01

    This paper critically examines popular discourses of pedagogy circulating in adult education theory and practice: pedagogy as (heroic or nurturing) person, as prescriptive strategy, as political purpose, and as situated practices. I argue that problematic conceptions and desires can be identified across these discourses that lead to orientations…

  2. Children Make You Happier...and Poorer

    ERIC Educational Resources Information Center

    Bauman, Zygmunt

    2006-01-01

    This article, which formed the opening keynote address of the Fifth International Conference on Children's Spirituality, addresses the place of children in the globalized social economy. It begins by arguing that current attitudes in the West towards children are conditioned by several contradictions in consumerism. Children, no longer as…

  3. Failed Fertility Treatments, Poorer Heart Health Later?

    MedlinePlus

    ... women in the study, said lead researcher Dr. Jacob Udell. He is a cardiologist at Women's College ... in the CMAJ (Canadian Medical Association Journal) . SOURCES: Jacob Udell, M.D., MPH, cardiologist, Women's College Hospital, ...

  4. Collective dose-practical ways to estimate a dose matrix.

    PubMed

    Simmonds, Jane; Sihra, Kamaljit; Bexon, Antony

    2006-06-01

    It has been suggested that collective doses should be presented in the form of a 'dose matrix' giving information on the breakdown of collective dose in space and time and by population group. This paper is an initial attempt to provide such a breakdown by geographic region and time, and to give an idea of associated individual doses for routine discharges to atmosphere. This is done through the use of representative per-caput individual doses but these need to be supplemented by information on the individual doses received by the critical group for a full radiological impact assessment. The results show that it is important to distinguish between the different population groups for up to a few hundred years following the discharge. However, beyond this time the main contribution is from global circulation and this distinction is less important. The majority of the collective dose was found to be delivered at low levels of individual doses; the estimated per-caput dose rates were significantly less than 10(-5) Sv y(-1), a level of dose felt to give rise to a trivial risk to the exposed individual.

  5. Standardized radiological dose evaluations

    SciTech Connect

    Peterson, V.L.; Stahlnecker, E.

    1996-05-01

    Following the end of the Cold War, the mission of Rocky Flats Environmental Technology Site changed from production of nuclear weapons to cleanup. Authorization baseis documents for the facilities, primarily the Final Safety Analysis Reports, are being replaced with new ones in which accident scenarios are sorted into coarse bins of consequence and frequency, similar to the approach of DOE-STD-3011-94. Because this binning does not require high precision, a standardized approach for radiological dose evaluations is taken for all the facilities at the site. This is done through a standard calculation ``template`` for use by all safety analysts preparing the new documents. This report describes this template and its use.

  6. Aspects of the relationship between drug dose and drug effect.

    PubMed

    Peper, Abraham

    2009-02-09

    It is generally assumed that there exists a well-defined relationship between drug dose and drug effect and that this can be expressed by a dose-response curve. This paper argues that there is no such clear relation and that the dose-response curve provides only limited information about the drug effect. It is demonstrated that tolerance development during the measurement of the dose-response curve may cause major distortion of the curve and it is argued that the curve may only be used to indicate the response to the first administration of a drug, before tolerance has developed. The precise effect of a drug on an individual depends on the dynamic relation between several variables, particularly the level of tolerance, the dose anticipated by the organism and the actual drug dose. Simulations with a previously published mathematical model of drug tolerance demonstrate that the effect of a dose smaller than the dose the organism has developed tolerance to is difficult to predict and may be opposite to the action of the usual dose.

  7. HEDR model validation plan. Hanford Environmental Dose Reconstruction Project

    SciTech Connect

    Napier, B.A.; Gilbert, R.O.; Simpson, J.C.; Ramsdell, J.V. Jr.; Thiede, M.E.; Walters, W.H.

    1993-06-01

    The Hanford Environmental Dose Reconstruction (HEDR) Project has developed a set of computational ``tools`` for estimating the possible radiation dose that individuals may have received from past Hanford Site operations. This document describes the planned activities to ``validate`` these tools. In the sense of the HEDR Project, ``validation`` is a process carried out by comparing computational model predictions with field observations and experimental measurements that are independent of those used to develop the model.

  8. Multilateral analysis of increasing collective dose and new ALARA programme.

    PubMed

    Oumi, Tadashi; Morii, Yasuki; Imai, Toshirou

    2011-07-01

    JAPC (The Japan Atomic Power Company) is the only electric power company that operates different types of nuclear reactors in Japan; it operates two BWRs (boiling water reactors), one pressurised water reactor and one gas cooled reactor. JAPC has been conducting various activities aimed at reducing radiation dose received by workers for over 45 y. Recently, the collective dose resulting from periodic maintenance has increased at each plant because of the replacement of large equipment and the unexpected extension of the outage period. In particular, the collective dose at Tokai-2 is one of the highest among Japanese BWR plants((1)), owing to the replacement and strengthening of equipment to meet earthquake-proof requirements. In this study, the authors performed a multilateral analysis of unacceptably a large collective dose and devised a new ALARA programme that includes a 3D dose prediction map and the development of machines to assist workers.

  9. Biological effects and equivalent doses in radiotherapy: A software solution

    PubMed Central

    Voyant, Cyril; Julian, Daniel; Roustit, Rudy; Biffi, Katia; Lantieri, Céline

    2013-01-01

    Background The limits of TDF (time, dose, and fractionation) and linear quadratic models have been known for a long time. Medical physicists and physicians are required to provide fast and reliable interpretations regarding delivered doses or any future prescriptions relating to treatment changes. Aim We, therefore, propose a calculation interface under the GNU license to be used for equivalent doses, biological doses, and normal tumor complication probability (Lyman model). Materials and methods The methodology used draws from several sources: the linear-quadratic-linear model of Astrahan, the repopulation effects of Dale, and the prediction of multi-fractionated treatments of Thames. Results and conclusions The results are obtained from an algorithm that minimizes an ad-hoc cost function, and then compared to an equivalent dose computed using standard calculators in seven French radiotherapy centers. PMID:24936319

  10. PGWD: Integrating Personal Genome for Warfarin Dosing.

    PubMed

    Pan, Yidan; Cheng, Ronghai; Li, Zhoufang; Zhao, Yujun; He, Jiankui

    2016-03-01

    Warfarin is a drug normally used in the prevention of thrombosis and the formation of blood clots. The dosage of warfarin is strongly affected by genetic variants of CYP2C9 and VKORC1 genes. Current technologies for detecting the variants of these genes are mainly based on real-time PCR. In recent years, due to the rapidly dropping cost of whole genome sequencing and genotyping, more and more people get their whole genome sequenced or genotyped. However, current software for warfarin dosing prediction is based on low-throughput genetic information from either real-time PCR or melting curve methods. There is no bioinformatics tool available that can take the high-throughput genome sequencing data as input and determine the accurate dosage of warfarin. Here, we present PGWD, a web tool that analyzes personal genome sequencing data and integrates with clinical information for warfarin dosing.

  11. Epigenomic Adaptation to Low Dose Radiation

    SciTech Connect

    Gould, Michael N.

    2015-06-30

    The overall hypothesis of this grant application is that the adaptive responses elicited by low dose ionizing radiation (LDIR) result in part from heritable DNA methylation changes in the epigenome. In the final budget period at the University of Wisconsin-Madison, we will specifically address this hypothesis by determining if the epigenetically labile, differentially methylated regions (DMRs) that regulate parental-specific expression of imprinted genes are deregulated in agouti mice by low dose radiation exposure during gestation. This information is particularly important to ascertain given the 1) increased human exposure to medical sources of radiation; 2) increased number of people predicted to live and work in space; and 3) enhanced citizen concern about radiation exposure from nuclear power plant accidents and terrorist ‘dirty bombs.’

  12. Estimating radiation effective doses from whole body computed tomography scans based on U.S. soldier patient height and weight

    PubMed Central

    2011-01-01

    Background The purpose of this study is to explore how a patient's height and weight can be used to predict the effective dose to a reference phantom with similar height and weight from a chest abdomen pelvis computed tomography scan when machine-based parameters are unknown. Since machine-based scanning parameters can be misplaced or lost, a predictive model will enable the medical professional to quantify a patient's cumulative radiation dose. Methods One hundred mathematical phantoms of varying heights and weights were defined within an x-ray Monte Carlo based software code in order to calculate organ absorbed doses and effective doses from a chest abdomen pelvis scan. Regression analysis was used to develop an effective dose predictive model. The regression model was experimentally verified using anthropomorphic phantoms and validated against a real patient population. Results Estimates of the effective doses as calculated by the predictive model were within 10% of the estimates of the effective doses using experimentally measured absorbed doses within the anthropomorphic phantoms. Comparisons of the patient population effective doses show that the predictive model is within 33% of current methods of estimating effective dose using machine-based parameters. Conclusions A patient's height and weight can be used to estimate the effective dose from a chest abdomen pelvis computed tomography scan. The presented predictive model can be used interchangeably with current effective dose estimating techniques that rely on computed tomography machine-based techniques. PMID:22004072

  13. Quantification of Proton Dose Calculation Accuracy in the Lung

    SciTech Connect

    Grassberger, Clemens; Daartz, Juliane; Dowdell, Stephen; Ruggieri, Thomas; Sharp, Greg; Paganetti, Harald

    2014-06-01

    Purpose: To quantify the accuracy of a clinical proton treatment planning system (TPS) as well as Monte Carlo (MC)–based dose calculation through measurements and to assess the clinical impact in a cohort of patients with tumors located in the lung. Methods and Materials: A lung phantom and ion chamber array were used to measure the dose to a plane through a tumor embedded in the lung, and to determine the distal fall-off of the proton beam. Results were compared with TPS and MC calculations. Dose distributions in 19 patients (54 fields total) were simulated using MC and compared to the TPS algorithm. Results: MC increased dose calculation accuracy in lung tissue compared with the TPS and reproduced dose measurements in the target to within ±2%. The average difference between measured and predicted dose in a plane through the center of the target was 5.6% for the TPS and 1.6% for MC. MC recalculations in patients showed a mean dose to the clinical target volume on average 3.4% lower than the TPS, exceeding 5% for small fields. For large tumors, MC also predicted consistently higher V5 and V10 to the normal lung, because of a wider lateral penumbra, which was also observed experimentally. Critical structures located distal to the target could show large deviations, although this effect was highly patient specific. Range measurements showed that MC can reduce range uncertainty by a factor of ∼2: the average (maximum) difference to the measured range was 3.9 mm (7.5 mm) for MC and 7 mm (17 mm) for the TPS in lung tissue. Conclusion: Integration of Monte Carlo dose calculation techniques into the clinic would improve treatment quality in proton therapy for lung cancer by avoiding systematic overestimation of target dose and underestimation of dose to normal lung. In addition, the ability to confidently reduce range margins would benefit all patients by potentially lowering toxicity.

  14. Quantitative performance characterization of image quality and radiation dose for a CS 9300 dental cone beam computed tomography machine

    PubMed Central

    Abouei, Elham; Lee, Sierra; Ford, Nancy L.

    2015-01-01

    Abstract. This paper aims to characterize the radiation dose and image quality (IQ) performance of a dental cone beam computed tomography (CBCT) unit over a range of fields of view (FOV). IQ and dose were measured using a Carestream 9300 dental CBCT. Phantoms were positioned in the FOV to imitate clinical positioning. IQ was assessed by scanning a SEDENTEXCT IQ phantom, and images were analyzed in ImageJ. Dose index 1 was obtained using a thimble ionization chamber and SEDENTEXCT DI phantom. Mean gray values agreed within 93.5% to 99.7% across the images, with pixel-to-pixel fluctuations of 6% to 12.5%, with poorer uniformity and increased noise for child protocols. CNR was fairly constant across FOVs, with higher CNR for larger patient settings. The measured limiting spatial resolution agreed well with 10% MTF and bar pattern measurements. Dose was reduced for smaller patient settings within a given FOV; however, smaller FOVs obtained with different acquisition settings did not necessarily result in reduced dose. The use of patient-specific acquisition settings decreased the radiation dose for smaller patients, with minimal impact on the IQ. The full set of IQ and dose measurements is reported to allow dental professionals to compare the different FOV settings for clinical use. PMID:26587550

  15. Mutations induced in Tradescantia by small doses of X-rays and neutrons - Analysis of dose-response curves.

    NASA Technical Reports Server (NTRS)

    Sparrow, A. H.; Underbrink, A. G.; Rossi, H. H.

    1972-01-01

    Dose-response curves for pink somatic mutations in Tradescantia stamen hairs were analyzed after neutron and X-ray irradiation with doses ranging from a fraction of a rad to the region of saturation. The dose-effect relation for neutrons indicates a linear dependence from 0.01 to 8 rads; between 0.25 and 5 rads, a linear dependence is indicated for X-rays also. As a consequence the relative biological effectiveness reaches a constant value (about 50) at low doses. The observations are in good agreement with the predictions of the theory of dual radiation action and support its interpretation of the effects of radiation on higher organisms. The doubling dose of X-rays was found to be nearly 1 rad.

  16. Dose refinement. ARAC's role

    SciTech Connect

    Ellis, J. S.; Sullivan, T. J.; Baskett, R. L.

    1998-06-01

    The Atmospheric Release Advisory Capability (ARAC), located at the Lawrence Livermore National Laboratory, since the late 1970's has been involved in assessing consequences from nuclear and other hazardous material releases into the atmosphere. ARAC's primary role has been emergency response. However, after the emergency phase, there is still a significant role for dispersion modeling. This work usually involves refining the source term and, hence, the dose to the populations affected as additional information becomes available in the form of source term estimates release rates, mix of material, and release geometry and any measurements from passage of the plume and deposition on the ground. Many of the ARAC responses have been documented elsewhere. 1 Some of the more notable radiological releases that ARAC has participated in the post-emergency phase have been the 1979 Three Mile Island nuclear power plant (NPP) accident outside Harrisburg, PA, the 1986 Chernobyl NPP accident in the Ukraine, and the 1996 Japan Tokai nuclear processing plant explosion. ARAC has also done post-emergency phase analyses for the 1978 Russian satellite COSMOS 954 reentry and subsequent partial burn up of its on board nuclear reactor depositing radioactive materials on the ground in Canada, the 1986 uranium hexafluoride spill in Gore, OK, the 1993 Russian Tomsk-7 nuclear waste tank explosion, and lesser releases of mostly tritium. In addition, ARAC has performed a key role in the contingency planning for possible accidental releases during the launch of spacecraft with radioisotope thermoelectric generators (RTGs) on board (i.e. Galileo, Ulysses, Mars-Pathfinder, and Cassini), and routinely exercises with the Federal Radiological Monitoring and Assessment Center (FRMAC) in preparation for offsite consequences of radiological releases from NPPs and nuclear weapon accidents or incidents. Several accident post-emergency phase assessments are discussed in this paper in order to illustrate

  17. In defence of collective dose.

    PubMed

    Fairlie, I; Sumner, D

    2000-03-01

    Recent proposals for a new scheme of radiation protection leave little room for collective dose estimations. This article discusses the history and present use of collective doses for occupational, ALARA, EIS and other purposes with reference to practical industry papers and government reports. The linear no-threshold (LNT) hypothesis suggests that collective doses which consist of very small doses added together should be used. Moral and ethical questions are discussed, particularly the emphasis on individual doses to the exclusion of societal risks, uncertainty over effects into the distant future and hesitation over calculating collective detriments. It is concluded that for moral, practical and legal reasons, collective dose is a valid parameter which should continue to be used.

  18. Dose from slow negative muons.

    PubMed

    Siiskonen, T

    2008-01-01

    Conversion coefficients from fluence to ambient dose equivalent, from fluence to maximum dose equivalent and quality factors for slow negative muons are examined in detail. Negative muons, when stopped, produce energetic photons, electrons and a variety of high-LET particles. Contribution from each particle type to the dose equivalent is calculated. The results show that for the high-LET particles the details of energy spectra and decay yields are important for accurate dose estimates. For slow negative muons the ambient dose equivalent does not always yield a conservative estimate for the protection quantities. Especially, the skin equivalent dose is strongly underestimated if the radiation-weighting factor of unity for slow muons is used. Comparisons to earlier studies are presented.

  19. Estimation of radionuclide ingestion: Lessons from dose reconstruction for fallout from the Nevada Test Site

    SciTech Connect

    Breshears, D.D.; Whicker, F.W.; Kirchner, T.B.; Anspaugh, L.R.

    1994-09-01

    The United States conducted atmospheric testing of nuclear devices at the Nevada Test Site from 1951 through 1963. In 1979 the U.S. Department of Energy established the Off-Site Radiation Exposure Review Project to compile a data base related to health effects from nuclear testing and to reconstruct doses to public residing off of the Nevada Test Site. This project is the most comprehensive dose reconstruction project to date, and, since similar assessments are currently underway at several other locations within and outside the U.S., lessons from ORERP can be valuable. A major component of dose reconstruction is estimation of dose from radionuclide ingestion. The PATHWAY food-chain model was developed to estimate the amount of radionuclides ingested. For agricultural components of the human diet, PATHWAY predicts radionuclide concentrations and quantities ingested. To improve accuracy and model credibility, four components of model analysis were conducted: estimation of uncertainty in model predictions, estimation of sensitivity of model predictions to input parameters, and testing of model predictions against independent data (validation), and comparing predictions from PATHWAY with those from other models. These results identified strengths and weaknesses in the model and aided in establishing the confidence associated with model prediction, which is a critical component risk assessment and dose reconstruction. For fallout from the Nevada Test Site, by far, the largest internal doses were received by the thyroid. However, the predicted number of fatal cancers from ingestion dose was generally much smaller than the number predicted from external dose. The number of fatal cancers predicted from ingestion dose was also orders of magnitude below the normal projected cancer rate. Several lessons were learned during the study that are relevant to other dose reconstruction efforts.

  20. Model calculations of the radiation dose and LET spectra on LDEF and comparisons with flight data

    NASA Technical Reports Server (NTRS)

    Armstrong, T. W.; Colborn, B. L.; Benton, E. V.

    1996-01-01

    Ionizing radiation environment models, a 3-D spacecraft mass model, and radiation transport codes have been used to predict the radiation dose and linear energy transfer (LET) spectra measured at various locations on the LDEF satellite. The predictions are compared with thermoluminescent dosimeter measurements of the trapped proton and electron doses and with LET spectra measured by plastic nuclear track detectors. The predicted vs observed comparisons indicate some of the uncertainties of present ionizing radiation environment models for low Earth-orbit missions.

  1. Dose to medium versus dose to water as an estimator of dose to sensitive skeletal tissue

    NASA Astrophysics Data System (ADS)

    Walters, B. R. B.; Kramer, R.; Kawrakow, I.

    2010-08-01

    The purpose of this study is to determine whether dose to medium, Dm, or dose to water, Dw, provides a better estimate of the dose to the radiosensitive red bone marrow (RBM) and bone surface cells (BSC) in spongiosa, or cancellous bone. This is addressed in the larger context of the ongoing debate over whether Dm or Dw should be specified in Monte Carlo calculated radiotherapy treatment plans. The study uses voxelized, virtual human phantoms, FAX06/MAX06 (female/male), incorporated into an EGSnrc Monte Carlo code to perform Monte Carlo dose calculations during simulated irradiation by a 6 MV photon beam from an Elekta SL25 accelerator. Head and neck, chest and pelvis irradiations are studied. FAX06/MAX06 include precise modelling of spongiosa based on µCT images, allowing dose to RBM and BSC to be resolved from the dose to bone. Modifications to the FAX06/MAX06 user codes are required to score Dw and Dm in spongiosa. Dose uncertainties of ~1% (BSC, RBM) or ~0.5% (Dm, Dw) are obtained after up to 5 days of simulations on 88 CPUs. Clinically significant differences (>5%) between Dm and Dw are found only in cranial spongiosa, where the volume fraction of trabecular bone (TBVF) is high (55%). However, for spongiosa locations where there is any significant difference between Dm and Dw, comparisons of differential dose volume histograms (DVHs) and average doses show that Dw provides a better overall estimate of dose to RBM and BSC. For example, in cranial spongiosa the average Dm underestimates the average dose to sensitive tissue by at least 5%, while average Dw is within ~1% of the average dose to sensitive tissue. Thus, it is better to specify Dw than Dm in Monte Carlo treatment plans, since Dw provides a better estimate of dose to sensitive tissue in bone, the only location where the difference is likely to be clinically significant.

  2. REMEDIATION FACILITY WORKER DOSE ASSESSMENT

    SciTech Connect

    V. Arakali; E. Faillace

    2004-02-27

    The purpose of this design calculation is to estimate radiation doses received by personnel in the Remediation Facility performing operations to receive, prepare, open, repair, recover, disposition, and correct off-normal and non-standard conditions with casks, canisters, spent nuclear fuel (SNF) assemblies, and waste packages (WP). The specific scope of work contained in this calculation covers both collective doses and individual worker group doses on an annual basis, and includes the contributions due to external and internal radiation. The results of this calculation will be used to support the design of the Remediation Facility and provide occupational dose estimates for the License Application.

  3. Hanford Environmental Dose Reconstruction Project

    SciTech Connect

    Finch, S.M.; McMakin, A.H.

    1992-06-01

    The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The project is being managed and conducted by the Battelle Pacific Northwest Laboratories under contract with the Centers for Disease Control. The independent Technical Steering Panel (TSP) provides technical direction. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed, from release to impact on humans (dose estimates): source terms; environmental transport; environmental monitoring data; demography, food consumption, and agriculture; environmental pathways and dose estimates.

  4. Psychotropic dose equivalence in Japan.

    PubMed

    Inada, Toshiya; Inagaki, Ataru

    2015-08-01

    Psychotropic dose equivalence is an important concept when estimating the approximate psychotropic doses patients receive, and deciding on the approximate titration dose when switching from one psychotropic agent to another. It is also useful from a research viewpoint when defining and extracting specific subgroups of subjects. Unification of various agents into a single standard agent facilitates easier analytical comparisons. On the basis of differences in psychopharmacological prescription features, those of available psychotropic agents and their approved doses, and racial differences between Japan and other countries, psychotropic dose equivalency tables designed specifically for Japanese patients have been widely used in Japan since 1998. Here we introduce dose equivalency tables for: (i) antipsychotics; (ii) antiparkinsonian agents; (iii) antidepressants; and (iv) anxiolytics, sedatives and hypnotics available in Japan. Equivalent doses for the therapeutic effects of individual psychotropic compounds were determined principally on the basis of randomized controlled trials conducted in Japan and consensus among dose equivalency tables reported previously by psychopharmacological experts. As these tables are intended to merely suggest approximate standard values, physicians should use them with discretion. Updated information of psychotropic dose equivalence in Japan is available at http://www.jsprs.org/en/equivalence.tables/. [Correction added on 8 July 2015, after first online publication: A link to the updated information has been added.].

  5. Quantitative evaluation by measurement and modeling of the variations in dose distributions deposited in mobile targets.

    PubMed

    Ali, Imad; Alsbou, Nesreen; Taguenang, Jean-Michel; Ahmad, Salahuddin

    2017-03-03

    The objective of this study is to quantitatively evaluate variations of dose distributions deposited in mobile target by measurement and modeling. The effects of variation in dose distribution induced by motion on tumor dose coverage and sparing of normal tissues were investigated quantitatively. The dose distributions with motion artifacts were modeled considering different motion patterns that include (a) motion with constant speed and (b) sinusoidal motion. The model predictions of the dose distributions with motion artifacts were verified with measurement where the dose distributions from various plans that included three-dimensional conformal and intensity-modulated fields were measured with a multiple-diode-array detector (MapCheck2), which was mounted on a mobile platform that moves with adjustable motion parameters. For each plan, the dose distributions were then measured with MapCHECK2 using different motion amplitudes from 0-25 mm. In addition, mathematical modeling was developed to predict the variations in the dose distributions and their dependence on the motion parameters that included amplitude, frequency and phase for sinusoidal motions. The dose distributions varied with motion and depended on the motion pattern particularly the sinusoidal motion, which spread out along the direction of motion. Study results showed that in the dose region between isocenter and the 50% isodose line, the dose profile decreased with increase of the motion amplitude. As the range of motion became larger than the field length along the direction of motion, the dose profiles changes overall including the central axis dose and 50% isodose line. If the total dose was delivered over a time much longer than the periodic time of motion, variations in motion frequency and phase do not affect the dose profiles. As a result, the motion dose modeling developed in this study provided quantitative characterization of variation in the dose distributions induced by motion, which

  6. Marijuana Use Predicts Cognitive Performance on Tasks of Executive Function

    PubMed Central

    Dahlgren, Mary Kathryn; Sagar, Kelly A.; Racine, Megan T.; Dreman, Meredith W.; Gruber, Staci A.

    2016-01-01

    Objective: Despite growing evidence that chronic marijuana use is associated with cognitive impairment, particularly when use is initiated at an early age, national trends demonstrate significant decreases in the perceived risk of marijuana corresponding with increased use, especially among youth. The current study assessed the impact of marijuana use on executive function and whether patterns of marijuana use, including earlier age at onset, higher frequency, and increased magnitude of use, predict impairment. Method: Forty-four chronic, heavy marijuana smokers (37 male, 7 female) and 32 healthy, nonsmoking control participants (20 male, 12 female) recruited from the Greater Boston area completed two assessments of executive function: the Stroop Color Word Test and Wisconsin Card Sorting Test (WCST). Results: Marijuana smokers had poorer executive function relative to control participants, a between-group difference that was primarily driven by individuals with early onset of marijuana use (before age 16; n = 21); significance remained even when controlling for frequency and magnitude of use. Further, earlier age at marijuana onset and increased marijuana use predicted poorer neurocognitive performance, and perseverative errors on the WCST significantly predicted marijuana group membership. Conclusions: These findings underscore the impact of early onset of marijuana use on executive function impairment independent of increased frequency and magnitude of use. In addition, poorer performance on the WCST may serve as a neuropsychological marker for heavy marijuana users. These results highlight the need for additional research to identify predictors associated with early marijuana use, as exposure to marijuana during a period of developmental vulnerability may result in negative cognitive consequences. PMID:26997188

  7. SU-E-T-169: Characterization of Pacemaker/ICD Dose in SAVI HDR Brachytherapy

    SciTech Connect

    Kalavagunta, C; Lasio, G; Yi, B; Zhou, J; Lin, M

    2015-06-15

    Purpose: It is important to estimate dose to pacemaker (PM)/Implantable Cardioverter Defibrillator (ICD) before undertaking Accelerated Partial Breast Treatment using High Dose Rate (HDR) brachytherapy. Kim et al. have reported HDR PM/ICD dose using a single-source balloon applicator. To the authors knowledge, there have so far not been any published PM/ICD dosimetry literature for the Strut Adjusted Volume Implant (SAVI, Cianna Medical, Aliso Viejo, CA). This study aims to fill this gap by generating a dose look up table (LUT) to predict maximum dose to the PM/ICD in SAVI HDR brachytherapy. Methods: CT scans for 3D dosimetric planning were acquired for four SAVI applicators (6−1-mini, 6−1, 8−1 and 10−1) expanded to their maximum diameter in air. The CT datasets were imported into the Elekta Oncentra TPS for planning and each applicator was digitized in a multiplanar reconstruction window. A dose of 340 cGy was prescribed to the surface of a 1 cm expansion of the SAVI applicator cavity. Cartesian coordinates of the digitized applicator were determined in the treatment leading to the generation of a dose distribution and corresponding distance-dose prediction look up table (LUT) for distances from 2 to 15 cm (6-mini) and 2 to 20 cm (10–1).The deviation between the LUT doses and the dose to the cardiac device in a clinical case was evaluated. Results: Distance-dose look up table were compared to clinical SAVI plan and the discrepancy between the max dose predicted by the LUT and the clinical plan was found to be in the range (−0.44%, 0.74%) of the prescription dose. Conclusion: The distance-dose look up tables for SAVI applicators can be used to estimate the maximum dose to the ICD/PM, with a potential usefulness for quick assessment of dose to the cardiac device prior to applicator placement.

  8. A dose error evaluation study for 4D dose calculations

    NASA Astrophysics Data System (ADS)

    Milz, Stefan; Wilkens, Jan J.; Ullrich, Wolfgang

    2014-10-01

    Previous studies have shown that respiration induced motion is not negligible for Stereotactic Body Radiation Therapy. The intrafractional breathing induced motion influences the delivered dose distribution on the underlying patient geometry such as the lung or the abdomen. If a static geometry is used, a planning process for these indications does not represent the entire dynamic process. The quality of a full 4D dose calculation approach depends on the dose coordinate transformation process between deformable geometries. This article provides an evaluation study that introduces an advanced method to verify the quality of numerical dose transformation generated by four different algorithms. The used transformation metric value is based on the deviation of the dose mass histogram (DMH) and the mean dose throughout dose transformation. The study compares the results of four algorithms. In general, two elementary approaches are used: dose mapping and energy transformation. Dose interpolation (DIM) and an advanced concept, so called divergent dose mapping model (dDMM), are used for dose mapping. The algorithms are compared to the basic energy transformation model (bETM) and the energy mass congruent mapping (EMCM). For evaluation 900 small sample regions of interest (ROI) are generated inside an exemplary lung geometry (4DCT). A homogeneous fluence distribution is assumed for dose calculation inside the ROIs. The dose transformations are performed with the four different algorithms. The study investigates the DMH-metric and the mean dose metric for different scenarios (voxel sizes: 8 mm, 4 mm, 2 mm, 1 mm 9 different breathing phases). dDMM achieves the best transformation accuracy in all measured test cases with 3-5% lower errors than the other models. The results of dDMM are reasonable and most efficient in this study, although the model is simple and easy to implement. The EMCM model also achieved suitable results, but the approach requires a more complex

  9. Helical tomotherapy superficial dose measurements

    SciTech Connect

    Ramsey, Chester R.; Seibert, Rebecca M.; Robison, Benjamin; Mitchell, Martha

    2007-08-15

    Helical tomotherapy is a treatment technique that is delivered from a 6 MV fan beam that traces a helical path while the couch moves linearly into the bore. In order to increase the treatment delivery dose rate, helical tomotherapy systems do not have a flattening filter. As such, the dose distributions near the surface of the patient may be considerably different from other forms of intensity-modulated delivery. The purpose of this study was to measure the dose distributions near the surface for helical tomotherapy plans with a varying separation between the target volume and the surface of an anthropomorphic phantom. A hypothetical planning target volume (PTV) was defined on an anthropomorphic head phantom to simulate a 2.0 Gy per fraction IMRT parotid-sparing head and neck treatment of the upper neck nodes. A total of six target volumes were created with 0, 1, 2, 3, 4, and 5 mm of separation between the surface of the phantom and the outer edge of the PTV. Superficial doses were measured for each of the treatment deliveries using film placed in the head phantom and thermoluminescent dosimeters (TLDs) placed on the phantom's surface underneath an immobilization mask. In the 0 mm test case where the PTV extends to the phantom surface, the mean TLD dose was 1.73{+-}0.10 Gy (or 86.6{+-}5.1% of the prescribed dose). The measured superficial dose decreases to 1.23{+-}0.10 Gy (61.5{+-}5.1% of the prescribed dose) for a PTV-surface separation of 5 mm. The doses measured by the TLDs indicated that the tomotherapy treatment planning system overestimates superficial doses by 8.9{+-}3.2%. The radiographic film dose for the 0 mm test case was 1.73{+-}0.07 Gy, as compared to the calculated dose of 1.78{+-}0.05 Gy. Given the results of the TLD and film measurements, the superficial calculated doses are overestimated between 3% and 13%. Without the use of bolus, tumor volumes that extend to the surface may be underdosed. As such, it is recommended that bolus be added for these

  10. Accumulated Dose in Liver Stereotactic Body Radiotherapy: Positioning, Breathing, and Deformation Effects

    SciTech Connect

    Velec, Michael; Moseley, Joanne L.; Craig, Tim; Dawson, Laura A.; Brock, Kristy K.

    2012-07-15

    Purpose: To investigate the accumulated dose deviations to tumors and normal tissues in liver stereotactic body radiotherapy (SBRT) and investigate their geometric causes. Methods and Materials: Thirty previously treated liver cancer patients were retrospectively evaluated. Stereotactic body radiotherapy was planned on the static exhale CT for 27-60 Gy in 6 fractions, and patients were treated in free-breathing with daily cone-beam CT guidance. Biomechanical model-based deformable image registration accumulated dose over both the planning four-dimensional (4D) CT (predicted breathing dose) and also over each fraction's respiratory-correlated cone-beam CT (accumulated treatment dose). The contribution of different geometric errors to changes between the accumulated and predicted breathing dose were quantified. Results: Twenty-one patients (70%) had accumulated dose deviations relative to the planned static prescription dose >5%, ranging from -15% to 5% in tumors and -42% to 8% in normal tissues. Sixteen patients (53%) still had deviations relative to the 4D CT-predicted dose, which were similar in magnitude. Thirty-two tissues in these 16 patients had deviations >5% relative to the 4D CT-predicted dose, and residual setup errors (n = 17) were most often the largest cause of the deviations, followed by deformations (n = 8) and breathing variations (n = 7). Conclusion: The majority of patients had accumulated dose deviations >5% relative to the static plan. Significant deviations relative to the predicted breathing dose still occurred in more than half the patients, commonly owing to residual setup errors. Accumulated SBRT dose may be warranted to pursue further dose escalation, adaptive SBRT, and aid in correlation with clinical outcomes.

  11. Graphing Predictions

    ERIC Educational Resources Information Center

    Connery, Keely Flynn

    2007-01-01

    Graphing predictions is especially important in classes where relationships between variables need to be explored and derived. In this article, the author describes how his students sketch the graphs of their predictions before they begin their investigations on two laboratory activities: Distance Versus Time Cart Race Lab and Resistance; and…

  12. Dose, Plasma Level, and Treatment Outcome Among Methadone Patients in Shanghai, China.

    PubMed

    Jiang, Haifeng; Hillhouse, Maureen; Du, Jiang; Pan, Shujun; Alfonso, Ang; Wang, Jun; Zhou, Zhirong; Yuan, Weijun; Ling, Walter; Zhao, Min

    2016-12-01

    The purpose of this study was to investigate the blood levels of methadone in participants receiving methadone for the treatment of opioid dependence. After stabilization on methadone for four weeks, blood samples from 95 participants were collected between treatment weeks 4 and 12, before and after receiving doses of methadone, and its blood levels were measured. A multiple linear regression model was used to examine the association between methadone blood levels and the outcomes of methadone maintenance treatment (MMT). Outcome differences between participants who had high (≥2) or low (<2) peak-to-trough ratios were also compared using an independent sample t-test. The blood level of methadone was not correlated with the clinical outcome of MMT with the moderate range of doses given. However, the retention of patients who had a free peak-to-trough ratio >2 was significantly poorer than those whose ratio was <2. Thus, monitoring plasma methadone levels is unlikely to be effective for guiding dosing decisions in situations where compliance with MMT is already very high or when the methadone dose is no longer the dominant factor in determining the clinical outcome. However, monitoring plasma methadone levels is still helpful for guiding the dosage for patients with a rapid metabolism.

  13. Dose Calculation Accuracy of the Monte Carlo Algorithm for CyberKnife Compared with Other Commercially Available Dose Calculation Algorithms

    SciTech Connect

    Sharma, Subhash; Ott, Joseph Williams, Jamone; Dickow, Danny

    2011-01-01

    Monte Carlo dose calculation algorithms have the potential for greater accuracy than traditional model-based algorithms. This enhanced accuracy is particularly evident in regions of lateral scatter disequilibrium, which can develop during treatments incorporating small field sizes and low-density tissue. A heterogeneous slab phantom was used to evaluate the accuracy of several commercially available dose calculation algorithms, including Monte Carlo dose calculation for CyberKnife, Analytical Anisotropic Algorithm and Pencil Beam convolution for the Eclipse planning system, and convolution-superposition for the Xio planning system. The phantom accommodated slabs of varying density; comparisons between planned and measured dose distributions were accomplished with radiochromic film. The Monte Carlo algorithm provided the most accurate comparison between planned and measured dose distributions. In each phantom irradiation, the Monte Carlo predictions resulted in gamma analysis comparisons >97%, using acceptance criteria of 3% dose and 3-mm distance to agreement. In general, the gamma analysis comparisons for the other algorithms were <95%. The Monte Carlo dose calculation algorithm for CyberKnife provides more accurate dose distribution calculations in regions of lateral electron disequilibrium than commercially available model-based algorithms. This is primarily because of the ability of Monte Carlo algorithms to implicitly account for tissue heterogeneities, density scaling functions; and/or effective depth correction factors are not required.

  14. Dose calculation accuracy of the Monte Carlo algorithm for CyberKnife compared with other commercially available dose calculation algorithms.

    PubMed

    Sharma, Subhash; Ott, Joseph; Williams, Jamone; Dickow, Danny

    2011-01-01

    Monte Carlo dose calculation algorithms have the potential for greater accuracy than traditional model-based algorithms. This enhanced accuracy is particularly evident in regions of lateral scatter disequilibrium, which can develop during treatments incorporating small field sizes and low-density tissue. A heterogeneous slab phantom was used to evaluate the accuracy of several commercially available dose calculation algorithms, including Monte Carlo dose calculation for CyberKnife, Analytical Anisotropic Algorithm and Pencil Beam convolution for the Eclipse planning system, and convolution-superposition for the Xio planning system. The phantom accommodated slabs of varying density; comparisons between planned and measured dose distributions were accomplished with radiochromic film. The Monte Carlo algorithm provided the most accurate comparison between planned and measured dose distributions. In each phantom irradiation, the Monte Carlo predictions resulted in gamma analysis comparisons >97%, using acceptance criteria of 3% dose and 3-mm distance to agreement. In general, the gamma analysis comparisons for the other algorithms were <95%. The Monte Carlo dose calculation algorithm for CyberKnife provides more accurate dose distribution calculations in regions of lateral electron disequilibrium than commercially available model-based algorithms. This is primarily because of the ability of Monte Carlo algorithms to implicitly account for tissue heterogeneities, density scaling functions; and/or effective depth correction factors are not required.

  15. Single daily dosing of aminoglycosides.

    PubMed

    Preston, S L; Briceland, L L

    1995-01-01

    To evaluate the rationale behind dosing aminoglycosides as a single daily dose versus traditional dosing approaches, we conducted a MEDLINE search to identify all pertinent articles, and also reviewed the references of all articles. Single daily dosing of aminoglycosides is not a new concept, having been examined since 1974. The advantages of this regimen include optimum concentration-dependent bactericidal activity, longer dosing intervals due to the postantibiotic effect (PAE), and prevention of bacterial adaptive resistance. Because of longer dosing intervals, toxicity may also be delayed or reduced. Costs may be reduced due to decreased monitoring and administration. Clinically, the regimen has been implemented in various patient populations with reported success. Questions remain, however, about optimum dose, peak and trough serum concentrations, and dose adjustment in patients with renal impairment or neutropenia. More clinical experience with this method in large numbers of patients has to be published. Pharmacists can be instrumental in monitoring patients receiving once-daily therapy and by educating health care professionals as to the rationale behind the therapy.

  16. Bayesian estimation of dose thresholds

    NASA Technical Reports Server (NTRS)

    Groer, P. G.; Carnes, B. A.

    2003-01-01

    An example is described of Bayesian estimation of radiation absorbed dose thresholds (subsequently simply referred to as dose thresholds) using a specific parametric model applied to a data set on mice exposed to 60Co gamma rays and fission neutrons. A Weibull based relative risk model with a dose threshold parameter was used to analyse, as an example, lung cancer mortality and determine the posterior density for the threshold dose after single exposures to 60Co gamma rays or fission neutrons from the JANUS reactor at Argonne National Laboratory. The data consisted of survival, censoring times and cause of death information for male B6CF1 unexposed and exposed mice. The 60Co gamma whole-body doses for the two exposed groups were 0.86 and 1.37 Gy. The neutron whole-body doses were 0.19 and 0.38 Gy. Marginal posterior densities for the dose thresholds for neutron and gamma radiation were calculated with numerical integration and found to have quite different shapes. The density of the threshold for 60Co is unimodal with a mode at about 0.50 Gy. The threshold density for fission neutrons declines monotonically from a maximum value at zero with increasing doses. The posterior densities for all other parameters were similar for the two radiation types.

  17. Repair of sublethal radiation injury after multiple small doses in mouse kidney: an estimate of flexure dose

    SciTech Connect

    Stewart, F.A.; Oussoren, Y.; Luts, A.; Begg, A.C.; Dewit, L.; Lebesque, J.; Bartelink, H.

    1987-05-01

    Functional kidney damage in mice was measured after a series of fractionated X-irradiations. Doses per fraction of 0.75-12.5 Gy were given as 2, 5, 10, 30, 40, 60, or 80 equal doses in a total treatment time of 4 weeks. Renal function (measured by clearance of /sup 51/CrEDTA or hematocrit levels) deteriorated progressively, in a dose related manner, from 20 to 46 weeks after the start of treatment. The changes in renal function versus time were fitted by a polynomial regression through all data and interpolated values for /sup 51/CrEDTA clearance were then calculated at 30 and 40 weeks after treatment. Steep dose response curves were obtained and these were used to calculate isoeffective doses for the different fractionation schedules. There was a marked increase in total isoeffective doses from 2-30 fractions and these data were well described by a linear quadratic (L.Q.) expression for damage with an alpha/beta ratio of 2.3 +/- 0.2 Gy. There was only a slight increase in the total isoeffect dose as the size of the dose per fraction was decreased below 2 Gy and the measured isoeffect doses after 40 to 80 fractions were lower than predicted on the basis of an L.Q. model assuming complete repair between successive irradiations. The flexure dose for mouse kidneys irradiated 3 times per day was, effectively, 1 to 2 Gy and hyperfractionation using lower doses per fraction did not lead to significant, additional repair.

  18. Phage therapy pharmacology: calculating phage dosing.

    PubMed

    Abedon, Stephen

    2011-01-01

    Phage therapy, which can be described as a phage-mediated biocontrol of bacteria (or, simply, biocontrol), is the application of bacterial viruses-also bacteriophages or phages-to reduce densities of nuisance or pathogenic bacteria. Predictive calculations for phage therapy dosing should be useful toward rational development of therapeutic as well as biocontrol products. Here, I consider the theoretical basis of a number of concepts relevant to phage dosing for phage therapy including minimum inhibitory concentration (but also "inundation threshold"), minimum bactericidal concentration (but also "clearance threshold"), decimal reduction time (D value), time until bacterial eradication, threshold bacterial density necessary to support phage population growth ("proliferation threshold"), and bacterial density supporting half-maximal phage population growth rates (K(B)). I also address the concepts of phage killing titers, multiplicity of infection, and phage peak densities. Though many of the presented ideas are not unique to this chapter, I nonetheless provide variations on derivations and resulting formulae, plus as appropriate discuss relative importance. The overriding goal is to present a variety of calculations that are useful toward phage therapy dosing so that they may be found in one location and presented in a manner that allows facile appreciation, comparison, and implementation. The importance of phage density as a key determinant of the phage potential to eradicate bacterial targets is stressed throughout the chapter.

  19. Hanford Environmental Dose Reconstruction Project

    SciTech Connect

    Finch, S.M.

    1990-09-01

    This monthly report summarizes the technical progress and project status for the Hanford Environmental Dose Reconstruction (HEDR) Project being conducted at the Pacific Northwest Laboratory (PNL) under the direction of a Technical Steering Panel (TSP). The TSP is composed of experts in numerous technical fields related to this project and represents the interests of the public. The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doses that populations could have received from nuclear operations at Hanford since 1944. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed, from release to impact on humans (dose estimates): source terms, environmental transport, environmental monitoring data, demographics, agriculture, food habits, environmental pathways and dose estimates. 3 figs.

  20. Exercise Dose in Clinical Practice.

    PubMed

    Wasfy, Meagan M; Baggish, Aaron L

    2016-06-07

    There is wide variability in the physical activity patterns of the patients in contemporary clinical cardiovascular practice. This review is designed to address the impact of exercise dose on key cardiovascular risk factors and on mortality. We begin by examining the body of literature that supports a dose-response relationship between exercise and cardiovascular disease risk factors, including plasma lipids, hypertension, diabetes mellitus, and obesity. We next explore the relationship between exercise dose and mortality by reviewing the relevant epidemiological literature underlying current physical activity guideline recommendations. We then expand this discussion to critically examine recent data pertaining to the impact of exercise dose at the lowest and highest ends of the spectrum. Finally, we provide a framework for how the key concepts of exercise dose can be integrated into clinical practice.

  1. Is it sensible to 'deform' dose? 3D experimental validation of dose-warping

    SciTech Connect

    Yeo, U. J.; Taylor, M. L.; Supple, J. R.; Smith, R. L.; Dunn, L.; Kron, T.; Franich, R. D.

    2012-08-15

    the square field case, the smallest deformation ({approx}9 mm) yields agreement of {gamma}{sub 3%/3mm}= 99.9%, while the most significant deformation ({approx}20 mm) yields agreement of {gamma}{sub 3%/3mm}= 96.7%. Conclusions: We have confirmed that, for a range of mass and density conserving deformations representative of those observable in anatomical targets, DIR-based dose-warping can yield accurate predictions of the dose distribution. Substantial differences can be seen between the results of different algorithms indicating that DIR performance should be scrutinized before application todose-warping. We have demonstrated that the DEFGEL deformable dosimeter can be used to evaluate DIR performance and the accuracy of dose-warping results by direct measurement.

  2. Peanut Allergen Threshold Study (PATS): validation of eliciting doses using a novel single-dose challenge protocol

    PubMed Central

    2013-01-01

    Background The eliciting dose (ED) for a peanut allergic reaction in 5% of the peanut allergic population, the ED05, is 1.5 mg of peanut protein. This ED05 was derived from oral food challenges (OFC) that use graded, incremental doses administered at fixed time intervals. Individual patients’ threshold doses were used to generate population dose-distribution curves using probability distributions from which the ED05 was then determined. It is important to clinically validate that this dose is predictive of the allergenic response in a further unselected group of peanut-allergic individuals. Methods/Aims This is a multi-centre study involving three national level referral and teaching centres. (Cork University Hospital, Ireland, Royal Children’s Hospital Melbourne, Australia and Massachusetts General Hospital, Boston, U.S.A.) The study is now in process and will continue to run until all centres have recruited 125 participates in each respective centre. A total of 375 participants, aged 1–18 years will be recruited during routine Allergy appointments in the centres. The aim is to assess the precision of the predicted ED05 using a single dose (6 mg peanut = 1.5 mg of peanut protein) in the form of a cookie. Validated Food Allergy related Quality of Life Questionnaires-(FAQLQ) will be self-administered prior to OFC and 1 month after challenge to assess the impact of a single dose OFC on FAQL. Serological and cell based in vitro studies will be performed. Conclusion The validation of the ED05 threshold for allergic reactions in peanut allergic subjects has potential value for public health measures. The single dose OFC, based upon the statistical dose-distribution analysis of past challenge trials, promises an efficient approach to identify the most highly sensitive patients within any given food-allergic population. PMID:24028324

  3. Cardiovascular risks associated with low dose ionizing particle radiation.

    PubMed

    Yan, Xinhua; Sasi, Sharath P; Gee, Hannah; Lee, JuYong; Yang, Yongyao; Mehrzad, Raman; Onufrak, Jillian; Song, Jin; Enderling, Heiko; Agarwal, Akhil; Rahimi, Layla; Morgan, James; Wilson, Paul F; Carrozza, Joseph; Walsh, Kenneth; Kishore, Raj; Goukassian, David A

    2014-01-01

    Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton ((1)H; 0.5 Gy, 1 GeV) and iron ion ((56)Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in (56)Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, (56)Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.

  4. Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

    DOE PAGES

    Yan, Xinhua; Sasi, Sharath P.; Gee, Hannah; ...

    2014-10-22

    Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton (1H; 0.5 Gy, 1 GeV) and iron ion (56Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiated mice initiallymore » improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in 56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, 56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Finally, understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.« less

  5. Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

    SciTech Connect

    Yan, Xinhua; Sasi, Sharath P.; Gee, Hannah; Lee, JuYong; Yang, Yongyao; Mehrzad, Raman; Onufrak, Jillian; Song, Jin; Enderling, Heiko; Agarwal, Akhil; Rahimi, Layla; Morgan, James; Wilson, Paul F.; Carrozza, Joseph; Walsh, Kenneth; Kishore, Raj; Goukassian, David A.

    2014-10-22

    Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton (1H; 0.5 Gy, 1 GeV) and iron ion (56Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in 56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, 56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Finally, understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.

  6. Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

    PubMed Central

    Yan, Xinhua; Sasi, Sharath P.; Gee, Hannah; Lee, JuYong; Yang, Yongyao; Mehrzad, Raman; Onufrak, Jillian; Song, Jin; Enderling, Heiko; Agarwal, Akhil; Rahimi, Layla; Morgan, James; Wilson, Paul F.; Carrozza, Joseph; Walsh, Kenneth; Kishore, Raj; Goukassian, David A.

    2014-01-01

    Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton (1H; 0.5 Gy, 1 GeV) and iron ion (56Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in 56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, 56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy. PMID:25337914

  7. Space radiation absorbed dose distribution in a human phantom

    NASA Technical Reports Server (NTRS)

    Badhwar, G. D.; Atwell, W.; Badavi, F. F.; Yang, T. C.; Cleghorn, T. F.

    2002-01-01

    -rate predictions are 20% lower than the observations. Assuming that the trapped-belt models lead to a correct orbit-averaged energy spectrum, the measurements of dose rates inside the phantom cannot be fully understood. Passive measurements using 6Li- and 7Li-based detectors on the astronauts and inside the brain and thyroid of the phantom show the presence of a significant contribution due to thermal neutrons, an area requiring additional study.

  8. Space radiation absorbed dose distribution in a human phantom.

    PubMed

    Badhwar, G D; Atwell, W; Badavi, F F; Yang, T C; Cleghorn, T F

    2002-01-01

    -rate predictions are 20% lower than the observations. Assuming that the trapped-belt models lead to a correct orbit-averaged energy spectrum, the measurements of dose rates inside the phantom cannot be fully understood. Passive measurements using 6Li- and 7Li-based detectors on the astronauts and inside the brain and thyroid of the phantom show the presence of a significant contribution due to thermal neutrons, an area requiring additional study.

  9. Pseudomonas aeruginosa dose response and bathing water infection.

    PubMed

    Roser, D J; van den Akker, B; Boase, S; Haas, C N; Ashbolt, N J; Rice, S A

    2014-03-01

    Pseudomonas aeruginosa is the opportunistic pathogen mostly implicated in folliculitis and acute otitis externa in pools and hot tubs. Nevertheless, infection risks remain poorly quantified. This paper reviews disease aetiologies and bacterial skin colonization science to advance dose-response theory development. Three model forms are identified for predicting disease likelihood from pathogen density. Two are based on Furumoto & Mickey's exponential 'single-hit' model and predict infection likelihood and severity (lesions/m2), respectively. 'Third-generation', mechanistic, dose-response algorithm development is additionally scoped. The proposed formulation integrates dispersion, epidermal interaction, and follicle invasion. The review also details uncertainties needing consideration which pertain to water quality, outbreaks, exposure time, infection sites, biofilms, cerumen, environmental factors (e.g. skin saturation, hydrodynamics), and whether P. aeruginosa is endogenous or exogenous. The review's findings are used to propose a conceptual infection model and identify research priorities including pool dose-response modelling, epidermis ecology and infection likelihood-based hygiene management.

  10. Development of PET imaging-based dose-painting prescriptions

    NASA Astrophysics Data System (ADS)

    Bowen, Stephen R.

    Historically, prescriptions in radiation therapy are based on physician experience drawn from the results of extensive clinical trials in order to establish standard-of-care guidelines. The doses of radiation are generally uniform across target volumes to reflect a fixed level of local neoplastic disease control of the population mean. However, inter-patient and intra-tumor variation in response to uniform doses can result in diminished tumor control and poor clinical outcome for certain patients. Recent research endeavors are emphasizing the need to individualize prescriptions by incorporating patient-specific biological markers with prognostic and predictive value. Quantitative imaging with positron emission tomography (PET) of tumor glucose metabolism, cell proliferation, and hypoxia has been suggested as a sensitive and specific technique to tailor patient prescriptions in a manner that may significantly improve clinical outcome. The concept of prescribing and delivering non-uniform dose based on molecular imaging, termed dose painting, hinges on the establishment of a dose-response relationship at the image voxel scale that optimizes a particular clinical endpoint. This doctoral thesis presented two methods of defining dose-painting prescriptions based on PET imaging: the first was a heuristic model derivation of hypoxia dose-painting prescriptions in head-and-neck cancer patients; the second was an empirical imaging surrogate endpoint derivation of prescriptions in veterinary sinonasal cancer patients. The clinical implementation of these dose painting prescriptions was investigated, which emphasized treatment planning and delivery solutions. Lastly, a summary and discussion of the future of dose painting to forge links between tumor biology and clinical outcome was presented. The compelling dose painting concept is fast becoming a clinical reality that may positively impact cancer patient lives.

  11. Radiation dose assessment of exposure to depleted uranium.

    PubMed

    Li, Wei Bo; Gerstmann, Udo C; Höllriegl, Vera; Szymczak, Wilfried; Roth, Paul; Hoeschen, Christoph; Oeh, Uwe

    2009-07-01

    Depleted uranium (DU) is claimed to contribute to human health problems, known as the Gulf War Syndrome and the Balkan Syndrome. Quantitative radiation dose is required to estimate the health risk of DU materials. The influences of the solubility parameters in the human alimentary tract and the respiratory tract systems and the aerosol particles size on the radiation dose of DU materials were evaluated. The dose conversion factor of daily urinary excretion of DU is provided. The retention and excretion of DU in the human body after a contamination at a wound site were predicted. Dose coefficients of DU after ingestion and inhalation were calculated using the solubility parameters of the DU corrosion products in simulated gastric and simulated lung fluid, which were determined in the Helmholtz Zentrum München. (238)U is the main radiation dose contributor per 1 Bq of DU materials. The dose coefficients of DU materials were estimated to be 3.5 x 10(-8) and 2.1 x 10(-6) Sv Bq(-1) after ingestion and inhalation for members of the public. The ingestion dose coefficient of DU materials is about 75% of the natural uranium value. The inhalation dose coefficient of DU material is in between those for Type M and Type S according to the category for inhaled materials defined by the International Commission on Radiological Protection. Radiation dose possibly received from DU materials can directly be estimated by using the dose conversion factor provided in this study, if daily urinary excretion of DU is measured.

  12. GAMMA DOSE RATE NEAR A NEW (252)Cf BRACHYTHERAPY SOURCE

    SciTech Connect

    Fortune, Eugene C; Gauld, Ian C; Wang, C

    2011-01-01

    A new generation of medical grade (252)Cf sources was developed in 2002 at the Oak Ridge National Laboratory. The combination of small size and large activity of (252)Cf makes the new source suitable to be used with the conventional high-dose-rate remote afterloading system for interstitial brachytherapy. A recent in-water calibration experiment showed that the measured gamma dose rates near the new source are slightly greater than the neutron dose rates, contradicting the well established neutron-to-gamma dose ratio of approximately 2:1 at locations near a (252)Cf brachytherapy source. Specifically, the MCNP-predicted gamma dose rate is a factor of two lower than the measured gamma dose rate at the distance of I cm, and the differences between the two results gradually diminish at distances farther away from the source. To resolve this discrepancy, we updated the source gamma spectrum by including in the ORIGEN-S data library the experimentally measured (252)Cf prompt gamma spectrum as well as the true (252)Cf spontaneous fission yield data to explicitly model delayed gamma emissions from fission products. We also investigated the bremsstrahlung X-rays produced by the beta particles emitted from fission product decays. The results show that the discrepancy of gamma dose rates is mainly caused by the omission of the bremsstrahlung X-rays in the MCNP runs. By including the bremsstrahlung X-rays, the MCNP results show that the gamma dose rates near a new (252)Cf source agree well with the measured results and that the gamma dose rates are indeed greater than the neutron dose rates.

  13. Radiation dose estimates for radiopharmaceuticals

    SciTech Connect

    Stabin, M.G.; Stubbs, J.B.; Toohey, R.E.

    1996-04-01

    Tables of radiation dose estimates based on the Cristy-Eckerman adult male phantom are provided for a number of radiopharmaceuticals commonly used in nuclear medicine. Radiation dose estimates are listed for all major source organs, and several other organs of interest. The dose estimates were calculated using the MIRD Technique as implemented in the MIRDOSE3 computer code, developed by the Oak Ridge Institute for Science and Education, Radiation Internal Dose Information Center. In this code, residence times for source organs are used with decay data from the MIRD Radionuclide Data and Decay Schemes to produce estimates of radiation dose to organs of standardized phantoms representing individuals of different ages. The adult male phantom of the Cristy-Eckerman phantom series is different from the MIRD 5, or Reference Man phantom in several aspects, the most important of which is the difference in the masses and absorbed fractions for the active (red) marrow. The absorbed fractions for flow energy photons striking the marrow are also different. Other minor differences exist, but are not likely to significantly affect dose estimates calculated with the two phantoms. Assumptions which support each of the dose estimates appears at the bottom of the table of estimates for a given radiopharmaceutical. In most cases, the model kinetics or organ residence times are explicitly given. The results presented here can easily be extended to include other radiopharmaceuticals or phantoms.

  14. Scoping assessment of radiological doses to aquatic organisms and wildlife -- N Springs

    SciTech Connect

    Poston, T.M.; Soldat, J.K.

    1992-10-01

    Estimated does rates were determined for endemic biota inhabiting the N Springs area based primarily on spring water data collected from the first 6 months of 1991. Radiological dose estimates were computed from measured values of specific radionuclides and modeled levels of radionuclides using established computer codes. The highest doses were predicted in hypothetical populations of clams, fish-eating ducks, and rabbits. The calculated dose estimates did not exceed 1 rad/d, an administrative dose rate established by the US Department of Energy for the protection of native aquatic biota. An administrative dose rate has not been established for terrestrial wildlife.

  15. Scoping assessment of radiological doses to aquatic organisms and wildlife -- N Springs. [N Springs

    SciTech Connect

    Poston, T.M.; Soldat, J.K.

    1992-10-01

    Estimated does rates were determined for endemic biota inhabiting the N Springs area based primarily on spring water data collected from the first 6 months of 1991. Radiological dose estimates were computed from measured values of specific radionuclides and modeled levels of radionuclides using established computer codes. The highest doses were predicted in hypothetical populations of clams, fish-eating ducks, and rabbits. The calculated dose estimates did not exceed 1 rad/d, an administrative dose rate established by the US Department of Energy for the protection of native aquatic biota. An administrative dose rate has not been established for terrestrial wildlife.

  16. Steroid dose sparing: pharmacodynamic responses to single versus divided doses of methylprednisolone in man.

    PubMed

    Reiss, W G; Slaughter, R L; Ludwig, E A; Middleton, E; Jusko, W J

    1990-06-01

    Inhibitory drug interactions affecting the metabolism of methylprednisolone (MP) may produce either steroid sparing or adverse effects partly by increasing the exposure time to the steroid. This phenomenon can be mimicked by administering MP in divided doses. Two types of responses were compared after a single MP dose (40 mg bolus) and a divided regimen (20 mg bolus and a 5 mg bolus 8 hours later) in six healthy male volunteers. The suppression of basophils measured as whole blood histamine and plasma cortisol concentrations was assessed during 32 hours. The 37.5% reduction in dose produced a 23% overall decreased blood histamine response. A pharmacodynamic model for basophil cell distribution to and from an extravascular compartment describes the effects of MP after both regimens. A slower initial decline in blood histamine after the divided regimen may be related to incomplete suppression of basophil cell return to blood. The 50% inhibitory concentrations of MP of about 5 ng/ml were similar for both regimens. The decline and return of cortisol concentrations were similar between MP treatments with suppression continuing for 24 hours. The 50% inhibitory concentrations of MP values for adrenal suppression were about 1 ng/ml. Pharmacodynamic modeling is useful in quantitating corticosteroid responses and generally predicted the "dose-sparing" effects that were achieved by prolonging MP plasma concentrations. This study supports previous clinical observations that patients may require morning through evening exposure to MP to optimize efficacy while adrenal suppression is being minimized.

  17. Radiation leakage dose from Elekta electron collimation system.

    PubMed

    Pitcher, Garrett M; Hogstrom, Kenneth R; Carver, Robert L

    2016-09-08

    This study provided baseline data required for a greater project, whose objective was to design a new Elekta electron collimation system having significantly lighter electron applicators with equally low out-of field leakage dose. Specifically, off-axis dose profiles for the electron collimation system of our uniquely configured Elekta Infinity accelerator with the MLCi2 treatment head were measured and calculated for two primary purposes: 1) to evaluate and document the out-of-field leakage dose in the patient plane and 2) to validate the dose distributions calculated using a BEAMnrc Monte Carlo (MC) model for out-of-field dose profiles. Off-axis dose profiles were measured in a water phantom at 100 cm SSD for 1 and 2 cm depths along the in-plane, cross-plane, and both diagonal axes using a cylindrical ionization chamber with the 10 × 10 and 20 × 20 cm2 applicators and 7, 13, and 20 MeV beams. Dose distributions were calculated using a previously developed BEAMnrc MC model of the Elekta Infinity accelerator for the same beam energies and applicator sizes and compared with measurements. Measured results showed that the in-field beam flatness met our acceptance criteria (± 3% on major and ±4% on diagonal axes) and that out-of-field mean and maximum percent leakage doses in the patient plane met acceptance criteria as specified by the International Electrotechnical Commission (IEC). Cross-plane out-of-field dose profiles showed greater leakage dose than in-plane profiles, attributed to the curved edges of the upper X-ray jaws and multileaf collimator. Mean leakage doses increased with beam energy, being 0.93% and 0.85% of maximum central axis dose for the 10 × 10 and 20 × 20 cm2 applicators, respectively, at 20 MeV. MC calculations predicted the measured dose to within 0.1% in most profiles outside the radiation field; however, excluding model-ing of nontrimmer applicator components led to calculations exceeding measured data by as much as 0.2% for some regions

  18. Shuttle radiation dose measurements in the International Space Station orbits.

    PubMed

    Badhwar, Gautam D

    2002-01-01

    The International Space Station (ISS) is now a reality with the start of a permanent human presence on board. Radiation presents a serious risk to the health and safety of the astronauts, and there is a clear requirement for estimating their exposures prior to and after flights. Predictions of the dose rate at times other than solar minimum or solar maximum have not been possible, because there has been no method to calculate the trapped-particle spectrum at intermediate times. Over the last few years, a tissue-equivalent proportional counter (TEPC) has been flown at a fixed mid-deck location on board the Space Shuttle in 51.65 degrees inclination flights. These flights have provided data that cover the expected changes in the dose rates due to changes in altitude and changes in solar activity from the solar minimum to the solar maximum of the current 23rd solar cycle. Based on these data, a simple function of the solar deceleration potential has been derived that can be used to predict the galactic cosmic radiation (GCR) dose rates to within +/-10%. For altitudes to be covered by the ISS, the dose rate due to the trapped particles is found to be a power-law function, rho(-2/3), of the atmospheric density, rho. This relationship can be used to predict trapped dose rates inside these spacecraft to +/-10% throughout the solar cycle. Thus, given the shielding distribution for a location inside the Space Shuttle or inside an ISS module, this approach can be used to predict the combined GCR + trapped dose rate to better than +/-15% for quiet solar conditions.

  19. ORGAN DOSES AND EFFECTIVE DOSE FOR FIVE PET RADIOPHARMACEUTICALS.

    PubMed

    Andersson, Martin; Johansson, Lennart; Mattsson, Sören; Minarik, David; Leide-Svegborn, Sigrid

    2016-06-01

    Diagnostic investigations with positron-emitting radiopharmaceuticals are dominated by (18)F-fluorodeoxyglucose ((18)F-FDG), but other radiopharmaceuticals are also commercially available or under development. Five of them, which are all clinically important, are (18)F-fluoride, (18)F-fluoroethyltyrosine ((18)F-FET), (18)F-deoxyfluorothymidine ((18)F-FLT), (18)F-fluorocholine ((18)F-choline) and (11)C-raclopride. To estimate the potential risk of stochastic effects (mainly lethal cancer) to a population, organ doses and effective dose values were updated for all five radiopharmaceuticals. Dose calculations were performed using the computer program IDAC2.0, which bases its calculations on the ICRP/ICRU adult reference voxel phantoms and the tissue weighting factors from ICRP publication 103. The biokinetic models were taken from ICRP publication 128. For organ doses, there are substantial changes. The only significant change in effective dose compared with previous estimations was a 46 % reduction for (18)F-fluoride. The estimated effective dose in mSv MBq(-1) was 1.5E-02 for (18)F-FET, 1.5E-02 for (18)F-FLT, 2.0E-02 for (18)F-choline, 9.0E-03 for (18)F-fluoride and 4.4E-03 for (11)C-raclopride.

  20. TH-A-19A-03: Impact of Proton Dose Calculation Method On Delivered Dose to Lung Tumors: Experiments in Thorax Phantom and Planning Study in Patient Cohort

    SciTech Connect

    Grassberger, C; Daartz, J; Dowdell, S; Ruggieri, T; Sharp, G; Paganetti, H

    2014-06-15

    Purpose: Evaluate Monte Carlo (MC) dose calculation and the prediction of the treatment planning system (TPS) in a lung phantom and compare them in a cohort of 20 lung patients treated with protons. Methods: A 2-dimensional array of ionization chambers was used to evaluate the dose across the target in a lung phantom. 20 lung cancer patients on clinical trials were re-simulated using a validated Monte Carlo toolkit (TOPAS) and compared to the TPS. Results: MC increases dose calculation accuracy in lung compared to the clinical TPS significantly and predicts the dose to the target in the phantom within ±2%: the average difference between measured and predicted dose in a plane through the center of the target is 5.6% for the TPS and 1.6% for MC. MC recalculations in patients show a mean dose to the clinical target volume on average 3.4% lower than the TPS, exceeding 5% for small fields. The lower dose correlates significantly with aperture size and the distance of the tumor to the chest wall (Spearman's p=0.0002/0.004). For large tumors MC also predicts consistently higher V{sub 5} and V{sub 10} to the normal lung, due to a wider lateral penumbra, which was also observed experimentally. Critical structures located distal to the target can show large deviations, though this effect is very patient-specific. Conclusion: Advanced dose calculation techniques, such as MC, would improve treatment quality in proton therapy for lung cancer by avoiding systematic overestimation of target dose and underestimation of dose to normal lung. This would increase the accuracy of the relationships between dose and effect, concerning tumor control as well as normal tissue toxicity. As the role of proton therapy in the treatment of lung cancer continues to be evaluated in clinical trials, this is of ever-increasing importance. This work was supported by National Cancer Institute Grant R01CA111590.

  1. Analytic estimates of secondary neutron dose in proton therapy.

    PubMed

    Anferov, V

    2010-12-21

    Proton beam losses in various components of a treatment nozzle generate secondary neutrons, which bring unwanted out of field dose during treatments. The purpose of this study was to develop an analytic method for estimating neutron dose to a distant organ at risk during proton therapy. Based on radiation shielding calculation methods proposed by Sullivan, we developed an analytical model for converting the proton beam losses in the nozzle components and in the treatment volume into the secondary neutron dose at a point of interest. Using the MCNPx Monte Carlo code, we benchmarked the neutron dose rates generated by the proton beam stopped at various media. The Monte Carlo calculations confirmed the validity of the analytical model for simple beam stop geometry. The analytical model was then applied to neutron dose equivalent measurements performed on double scattering and uniform scanning nozzles at the Midwest Proton Radiotherapy Institute (MPRI). Good agreement was obtained between the model predictions and the data measured at MPRI. This work provides a method for estimating analytically the neutron dose equivalent to a distant organ at risk. This method can be used as a tool for optimizing dose delivery techniques in proton therapy.

  2. Measuring radiation dose to patients undergoing fluoroscopically-guided interventions

    NASA Astrophysics Data System (ADS)

    Lubis, L. E.; Badawy, M. K.

    2016-03-01

    The increasing prevalence and complexity of fluoroscopically guided interventions (FGI) raises concern regarding radiation dose to patients subjected to the procedure. Despite current evidence showing the risk to patients from the deterministic effects of radiation (e.g. skin burns), radiation induced injuries remain commonplace. This review aims to increase the awareness surrounding radiation dose measurement for patients undergoing FGI. A review of the literature was conducted alongside previous researches from the authors’ department. Studies pertaining to patient dose measurement, its formalism along with current advances and present challenges were reviewed. Current patient monitoring techniques (using available radiation dosimeters), as well as the inadequacy of accepting displayed dose as patient radiation dose is discussed. Furthermore, advances in real-time patient radiation dose estimation during FGI are considered. Patient dosimetry in FGI, particularly in real time, remains an ongoing challenge. The increasing occurrence and sophistication of these procedures calls for further advances in the field of patient radiation dose monitoring. Improved measuring techniques will aid clinicians in better predicting and managing radiation induced injury following FGI, thus improving patient care.

  3. Cytogenetic characterization of low-dose hyper-radiosensitivity in Cobalt-60 irradiated human lymphoblastoid cells.

    PubMed

    Joshi, Gnanada S; Joiner, Michael C; Tucker, James D

    2014-12-01

    The dose-effect relationships of cells exposed to ionizing radiation are frequently described by linear quadratic (LQ) models over an extended dose range. However, many mammalian cell lines, when acutely irradiated in G2 at doses ≤0.3Gy, show hyper-radiosensitivity (HRS) as measured by reduced clonogenic cell survival, thereby indicating greater cell lethality than is predicted by extrapolation from high-dose responses. We therefore hypothesized that the cytogenetic response in G2 cells to low doses would also be steeper than predicted by LQ extrapolation from high doses. We tested our hypothesis by exposing four normal human lymphoblastoid cell lines to 0-400cGy of Cobalt-60 gamma radiation. The cytokinesis block micronucleus assay was used to determine the frequencies of micronuclei and nucleoplasmic bridges. To characterize the dependence of the cytogenetic damage on dose, univariate and multivariate regression analyses were used to compare the responses in the low- (HRS) and high-dose response regions. Our data indicate that the slope of the response for all four cell lines at ≤20cGy during G2 is greater than predicted by an LQ extrapolation from the high-dose responses for both micronuclei and bridges. These results suggest that the biological consequences of low-dose exposures could be underestimated and may not provide accurate risk assessments following such exposures.

  4. Race influences warfarin dose changes associated with genetic factors.

    PubMed

    Limdi, Nita A; Brown, Todd M; Yan, Qi; Thigpen, Jonathan L; Shendre, Aditi; Liu, Nianjun; Hill, Charles E; Arnett, Donna K; Beasley, T Mark

    2015-07-23

    Warfarin dosing algorithms adjust for race, assigning a fixed effect size to each predictor, thereby attenuating the differential effect by race. Attenuation likely occurs in both race groups but may be more pronounced in the less-represented race group. Therefore, we evaluated whether the effect of clinical (age, body surface area [BSA], chronic kidney disease [CKD], and amiodarone use) and genetic factors (CYP2C9*2, *3, *5, *6, *11, rs12777823, VKORC1, and CYP4F2) on warfarin dose differs by race using regression analyses among 1357 patients enrolled in a prospective cohort study and compared predictive ability of race-combined vs race-stratified models. Differential effect of predictors by race was assessed using predictor-race interactions in race-combined analyses. Warfarin dose was influenced by age, BSA, CKD, amiodarone use, and CYP2C9*3 and VKORC1 variants in both races, by CYP2C9*2 and CYP4F2 variants in European Americans, and by rs12777823 in African Americans. CYP2C9*2 was associated with a lower dose only among European Americans (20.6% vs 3.0%, P < .001) and rs12777823 only among African Americans (12.3% vs 2.3%, P = .006). Although VKORC1 was associated with dose decrease in both races, the proportional decrease was higher among European Americans (28.9% vs 19.9%, P = .003) compared with African Americans. Race-stratified analysis improved dose prediction in both race groups compared with race-combined analysis. We demonstrate that the effect of predictors on warfarin dose differs by race, which may explain divergent findings reported by recent warfarin pharmacogenetic trials. We recommend that warfarin dosing algorithms should be stratified by race rather than adjusted for race.

  5. PREDICTIVE MODELS

    SciTech Connect

    Ray, R.M. )

    1986-12-01

    PREDICTIVE MODELS is a collection of five models - CFPM, CO2PM, ICPM, PFPM, and SFPM - used in the 1982-1984 National Petroleum Council study of enhanced oil recovery (EOR) potential. Each pertains to a specific EOR process designed to squeeze additional oil from aging or spent oil fields. The processes are: 1) chemical flooding, where soap-like surfactants are injected into the reservoir to wash out the oil; 2) carbon dioxide miscible flooding, where carbon dioxide mixes with the lighter hydrocarbons making the oil easier to displace; 3) in-situ combustion, which uses the heat from burning some of the underground oil to thin the product; 4) polymer flooding, where thick, cohesive material is pumped into a reservoir to push the oil through the underground rock; and 5) steamflood, where pressurized steam is injected underground to thin the oil. CFPM, the Chemical Flood Predictive Model, models micellar (surfactant)-polymer floods in reservoirs, which have been previously waterflooded to residual oil saturation. Thus, only true tertiary floods are considered. An option allows a rough estimate of oil recovery by caustic or caustic-polymer processes. CO2PM, the Carbon Dioxide miscible flooding Predictive Model, is applicable to both secondary (mobile oil) and tertiary (residual oil) floods, and to either continuous CO2 injection or water-alternating gas processes. ICPM, the In-situ Combustion Predictive Model, computes the recovery and profitability of an in-situ combustion project from generalized performance predictive algorithms. PFPM, the Polymer Flood Predictive Model, is switch-selectable for either polymer or waterflooding, and an option allows the calculation of the incremental oil recovery and economics of polymer relative to waterflooding. SFPM, the Steamflood Predictive Model, is applicable to the steam drive process, but not to cyclic steam injection (steam soak) processes.

  6. Hanford Environmental Dose Reconstruction Project

    SciTech Connect

    McMakin, A.H.; Cannon, S.D.; Finch, S.M.

    1992-07-01

    The objective of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The TSP consists of experts in environmental pathways, epidemiology, surface-water transport, ground-water transport, statistics, demography, agriculture, meteorology, nuclear engineering, radiation dosimetry, and cultural anthropology. Included are appointed technical members representing the states of Oregon, Washington, and Idaho, a representative of Native American tribes, and an individual representing the public. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed from release to impact on humans (dose estimates): Source terms, environmental transport, environmental monitoring data, demography, food consumption, and agriculture, and environmental pathways and dose estimates. Progress is discussed.

  7. Hanford Environmental Dose Reconstruction Project

    SciTech Connect

    Finch, S.M.; McMakin, A.H.

    1991-01-01

    The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation