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Sample records for 10-fold higher dose

  1. Improved Outcomes With Higher Doses for Salvage Radiotherapy After Prostatectomy

    SciTech Connect

    King, Christopher R. Spiotto, Michael T.

    2008-05-01

    Purpose: To evaluate relapse-free survival with higher doses for patients receiving salvage radiotherapy (RT) after radical prostatectomy (RP). Patients and Methods: A total of 122 patients with pathologically negative lymph nodes received salvage RT after RP from 1984 to 2004. Median prostate bed dose was 60 Gy for 38 patients and 70 Gy for 84 patients. Four months of total androgen suppression and whole-pelvic RT were given concurrently to 68 and 72 patients, respectively. The median follow-up was >5 years. Kaplan-Meier and Cox proportional hazards multivariable analyses were performed for all clinical, pathologic, and treatment factors predicting for biochemical relapse-free survival (bRFS). Results: There were 60 biochemical failures after salvage RT, with a median time to failure of 1.2 years. A dose response was observed, with a 5-year bRFS rate of 25% vs. 58% for prostate bed doses of 60 Gy vs. 70 Gy (p < 0.0001). For patients receiving RT alone the 5-year bRFS rate was 17% vs. 55% (p = 0.016), and for those receiving prostate-bed-only RT it was 23% vs. 66% (p = 0.037) for doses of 60 Gy vs. 70 Gy, respectively. On multivariate analysis a prostate bed dose of 70 Gy (p 0.012, hazard ratio [HR] 0.48 [95% Confidence Interval (CI), 0.27-0.87]), pre-RT prostate-specific antigen value {<=}1 ng/mL (p < 0.0001, HR 0.28 [95% CI, 0.16-0.48]), and lack of seminal vesicle involvement (p = 0.009, HR 0.44 [95% CI, 0.26-0.77]) remained independently significant. Conclusions: A clinically significant dose response from 60 Gy to 70 Gy was observed in the setting of salvage RT after prostatectomy. A dose of 70 Gy to the prostate bed is recommended to achieve optimal disease-free survival.

  2. Splenectomy Causes 10-Fold Increased Risk of Portal Venous System Thrombosis in Liver Cirrhosis Patients

    PubMed Central

    Qi, Xingshun; Han, Guohong; Ye, Chun; Zhang, Yongguo; Dai, Junna; Peng, Ying; Deng, Han; Li, Jing; Hou, Feifei; Ning, Zheng; Zhao, Jiancheng; Zhang, Xintong; Wang, Ran; Guo, Xiaozhong

    2016-01-01

    Background Portal venous system thrombosis (PVST) is a life-threatening complication of liver cirrhosis. We conducted a retrospective study to comprehensively analyze the prevalence and risk factors of PVST in liver cirrhosis. Material/Methods All cirrhotic patients without malignancy admitted between June 2012 and December 2013 were eligible if they underwent contrast-enhanced CT or MRI scans. Independent predictors of PVST in liver cirrhosis were calculated in multivariate analyses. Subgroup analyses were performed according to the severity of PVST (any PVST, main portal vein [MPV] thrombosis >50%, and clinically significant PVST) and splenectomy. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported. Results Overall, 113 cirrhotic patients were enrolled. The prevalence of PVST was 16.8% (19/113). Splenectomy (any PVST: OR=11.494, 95%CI=2.152–61.395; MPV thrombosis >50%: OR=29.987, 95%CI=3.247–276.949; clinically significant PVST: OR=40.415, 95%CI=3.895–419.295) and higher hemoglobin (any PVST: OR=0.974, 95%CI=0.953–0.996; MPV thrombosis >50%: OR=0.936, 95%CI=0.895–0.980; clinically significant PVST: OR=0.935, 95%CI=0.891–0.982) were the independent predictors of PVST. The prevalence of PVST was 13.3% (14/105) after excluding splenectomy. Higher hemoglobin was the only independent predictor of MPV thrombosis >50% (OR=0.952, 95%CI=0.909–0.997). No independent predictors of any PVST or clinically significant PVST were identified in multivariate analyses. Additionally, PVST patients who underwent splenectomy had a significantly higher proportion of clinically significant PVST but lower MELD score than those who did not undergo splenectomy. In all analyses, the in-hospital mortality was not significantly different between cirrhotic patient with and without PVST. Conclusions Splenectomy may increase by at least 10-fold the risk of PVST in liver cirrhosis independent of severity of liver dysfunction. PMID:27432511

  3. Warfarin maintenance dose in older patients: higher average dose and wider dose frequency distribution in patients of African ancestry than those of European ancestry.

    PubMed

    Garwood, Candice L; Clemente, Jennifer L; Ibe, George N; Kandula, Vijay A; Curtis, Kristy D; Whittaker, Peter

    2010-06-15

    Studies report that warfarin doses required to maintain therapeutic anticoagulation decrease with age; however, these studies almost exclusively enrolled patients of European ancestry. Consequently, universal application of dosing paradigms based on such evidence may be confounded because ethnicity also influences dose. Therefore, we determined if warfarin dose decreased with age in Americans of African ancestry, if older African and European ancestry patients required different doses, and if their daily dose frequency distributions differed. Our chart review examined 170 patients of African ancestry and 49 patients of European ancestry cared for in our anticoagulation clinic. We calculated the average weekly dose required for each stable, anticoagulated patient to maintain an international normalized ratio of 2.0 to 3.0, determined dose averages for groups <70, 70-79, and >80 years of age and plotted dose as a function of age. The maintenance dose in patients of African ancestry decreased with age (P<0.001). In addition, older patients of African ancestry required higher average weekly doses than patients of European ancestry: 33% higher in the 70- to 79-year-old group (38.2+/-1.9 vs. 28.8+/-1.7 mg; P=0.006) and 52% in the >80-year-old group (33.2+/-1.7 vs. 21.8+/-3.8 mg; P=0.011). Therefore, 43% of older patients of African ancestry required daily doses >5mg and hence would have been under-dosed using current starting-dose guidelines. The dose frequency distribution was wider for older patients of African ancestry compared to those of European ancestry (P<0.01). The higher doses required by older patients of African ancestry indicate that strategies for initiating warfarin therapy based on studies of patients of European ancestry could result in insufficient anticoagulation and thereby potentially increase their thromboembolism risk.

  4. CORRELATES OF HIGHER DOSE OPIOID MEDICATION USE FOR LOW BACK PAIN IN PRIMARY CARE

    PubMed Central

    Kobus, Amy M.; Smith, David H.; Morasco, Benjamin J.; Johnson, Eric S.; Yang, Xiuhai; Petrik, Amanda F.; Deyo, Richard A.

    2012-01-01

    Factors associated with high-dose opioid therapy for non-cancer pain are poorly understood. We document the prevalence of high-dose opioid use, as well as associated demographic, clinical, and health service utilization correlates among low back pain patients. Patients prescribed higher-dose opioids (≥100 mg/day morphine equivalent at last dispensing; n=453) and receiving opioids for 90+ consecutive days were compared to two groups: lower-dose (1–99 mg/day; n=4,815) or no opioid use (n=10,184). Higher-dose opioid use occurred in 2.9% of patients who received any opioids and in 8.6% of patients who received opioids long-term. The median dose in the higher-dose group was 180.0 mg/day. Compared to the no opioid group, higher-dose users reported poorer health. Compared to either comparison group, patients in the higher-dose group had higher rates of mental health and substance use disorders, concurrent sedative-hypnotic use (60.5%; n=274), and health service utilization. After adjusting for select covariates, male gender (Odds ratio (OR) 1.68, 95%CI 1.37,2.06), higher comorbidity, Medicare coverage (OR 1.65, 95% CI 1.22,2.23), any mental health or substance use diagnosis (OR 1.58, 95% CI 1.28,1.95), co-prescriptions of sedative-hypnotics (OR 1.75, 95% CI 1.42,2.16), and more Emergency Department and specialty pain clinic visits were associated with higher likelihood of high-dose prescriptions. PMID:23117108

  5. Tacrolimus dose requirement in renal transplant recipients is significantly higher when used in combination with corticosteroids

    PubMed Central

    Hesselink, Dennis A; Ngyuen, Hien; Wabbijn, Marike; Gregoor, Peter J H Smak; Steyerberg, Ewout W; van Riemsdijk, Iza C; Weimar, Willem; van Gelder, Teun

    2003-01-01

    Aims To evaluate the effect of corticosteroids on tacrolimus pharmacokinetics. Methods In a randomized trial, kidney transplant recipients were treated with tacrolimus and mycophenolate mofetil with either daclizumab (n = 31) or 3 months of prednisone (n = 34). Tacrolimus dose-adjusted predose concentrations (C0) at month 1–6 were compared between both groups and within the corticosteroid group before and after prednisone withdrawal. Results At month 1 the tacrolimus dose-adjusted C0 in the corticosteroid group was 83 ± 8 vs 119 ± 17 ng ml−1 mg−1 kg−1 in the daclizumab group. The tacrolimus dose-adjusted C0 within the corticosteroid group at month 1 and 2 was 42% and 29% lower compared with month 4 (P < 0.001). Conclusions A higher tacrolimus dose is required to reach target concentrations when used in combination with corticosteroids. PMID:12919182

  6. Do Glioma Patients Derive Any Therapeutic Benefit From Taking a Higher Cumulative Dose of Temozolomide Regimens?

    PubMed Central

    Sun, Hao; Du, Shasha; Liao, Guixiang; Xie, Xiao; Ren, Chen; Yuan, Ya Wei

    2015-01-01

    Abstract Temozolomide (TMZ) is an oral alkylating agent with established effects on the central nervous system of glioblastoma (GBM) patients. Clinical trials have demonstrated a significant impact on overall survival (OS) with TMZ. Ever since, several TMZ regimens have been designed to improve treatment efficacy by increasing the cumulative dose per cycle. We report a meta-analysis to systematically evaluate different treatment schedules of TMZ in GBM patients. All searches that were conducted in the Cochrane library, Science Direct, and PubMed Databases, and 3 randomized controlled trials (1141 patients) were included. OS and progression-free survival (PFS) were the primary outcomes to be pooled. Unexpectedly, this analysis did not reveal any OS or PFS advantage for the high cumulative dose (HCD) regimen compared with the normal cumulative dose regimen (1141 total patients; hazard ratio [HR] 1.07, 95% CI 0.94–1.22, P = 0.31). Then after analyzing the characteristics of the results from each trial, we found that the regimen with a higher peak concentration during a short-term period (daily doses ≥150 mg/m2/d within ≤7 days/cycle) always had a more superior clinical benefit. So we generated a new pooled HR of 1.10 with a 95% CI of 0.96–1.25 (P = 0.17), which prefers the high peak concentration schedule even without a significant difference. The adverse outcome also indicates a significant increased risk of leukopenia (risk ratio 1.59, 95% CI 1.03–2.46, P = 0.04) among the HCD group. Our study suggests that increasing the cumulative dose per cycle is not an ideal way to improve the efficacy of TMZ, and it will lead to increased risk for leukopenia. Future trials should be designed to examine schedules of higher peak concentration rather than the cumulative dose per cycle. PMID:25997057

  7. The lateral plane delivers higher dose than the frontal plane in biplane cardiac catheterization systems.

    PubMed

    Aldoss, Osamah; Patel, Sonali; Harris, Kyle; Divekar, Abhay

    2015-06-01

    The objective of the study is to compare radiation dose between the frontal and lateral planes in a biplane cardiac catheterization laboratory. Tube angulation progressively increases patient and operator radiation dose in single-plane cardiac catheterization laboratories. This retrospective study captured biplane radiation dose in a pediatric cardiac catheterization laboratory between April 2010 and January 2014. Raw and time-indexed fluoroscopic, cineangiographic and total (fluoroscopic + cineangiographic) air kerma (AK, mGy) and kerma area product (PKA, µGym(2)/Kg) for each plane were compared. Data for 716 patients were analyzed: 408 (56.98 %) were male, the median age was 4.86 years, and the median weight was 17.35 kg. Although median beam-on time (minutes) was 4.2 times greater in the frontal plane, there was no difference in raw median total PKA between the two planes. However, when indexed to beam-on time, the lateral plane had a higher median-indexed fluoroscopic (0.75 vs. 1.70), cineangiographic (16.03 vs. 24.92), and total (1.43 vs. 5.15) PKA (p < 0.0001). The median time-indexed total PKA in the lateral plane is 3.6 times the frontal plane. This is the first report showing that the lateral plane delivers a higher dose than the frontal plane per unit time. Operators should consciously reduce the lateral plane beam-on time and incorporate this practice in radiation reduction protocols.

  8. A single dose of oxytocin nasal spray improves higher-order social cognition in schizophrenia.

    PubMed

    Guastella, Adam J; Ward, Philip B; Hickie, Ian B; Shahrestani, Sara; Hodge, Marie Antoinette Redoblado; Scott, Elizabeth M; Langdon, Robyn

    2015-11-01

    Schizophrenia is associated with significant impairments in both higher and lower order social cognitive performance and these impairments contribute to poor social functioning. People with schizophrenia report poor social functioning to be one of their greatest unmet treatment needs. Recent studies have suggested the potential of oxytocin as such a treatment, but mixed results render it uncertain what aspects of social cognition are improved by oxytocin and, subsequently, how oxytocin might best be applied as a therapeutic. The aim of this study was to determine whether a single dose of oxytocin improved higher-order and lower-order social cognition performance for patients with schizophrenia across a well-established battery of social cognition tests. Twenty-one male patients received both a single dose of oxytocin nasal spray (24IU) and a placebo, two weeks apart in a randomized within-subjects placebo controlled design. Following each administration, participants completed the social cognition tasks, as well as a test of general neurocognition. Results revealed that oxytocin particularly enhanced performance on higher order social cognition tasks, with no effects on general neurocognition. Results for individual tasks showed most improvement on tests measuring appreciation of indirect hints and recognition of social faux pas. These results suggest that oxytocin, if combined to enhance social cognition learning, may be beneficial when targeted at higher order social cognition domains. This study also suggests that these higher order tasks, which assess social cognitive processing in a social communication context, may provide useful markers of response to oxytocin in schizophrenia.

  9. A single dose of oxytocin nasal spray improves higher-order social cognition in schizophrenia.

    PubMed

    Guastella, Adam J; Ward, Philip B; Hickie, Ian B; Shahrestani, Sara; Hodge, Marie Antoinette Redoblado; Scott, Elizabeth M; Langdon, Robyn

    2015-11-01

    Schizophrenia is associated with significant impairments in both higher and lower order social cognitive performance and these impairments contribute to poor social functioning. People with schizophrenia report poor social functioning to be one of their greatest unmet treatment needs. Recent studies have suggested the potential of oxytocin as such a treatment, but mixed results render it uncertain what aspects of social cognition are improved by oxytocin and, subsequently, how oxytocin might best be applied as a therapeutic. The aim of this study was to determine whether a single dose of oxytocin improved higher-order and lower-order social cognition performance for patients with schizophrenia across a well-established battery of social cognition tests. Twenty-one male patients received both a single dose of oxytocin nasal spray (24IU) and a placebo, two weeks apart in a randomized within-subjects placebo controlled design. Following each administration, participants completed the social cognition tasks, as well as a test of general neurocognition. Results revealed that oxytocin particularly enhanced performance on higher order social cognition tasks, with no effects on general neurocognition. Results for individual tasks showed most improvement on tests measuring appreciation of indirect hints and recognition of social faux pas. These results suggest that oxytocin, if combined to enhance social cognition learning, may be beneficial when targeted at higher order social cognition domains. This study also suggests that these higher order tasks, which assess social cognitive processing in a social communication context, may provide useful markers of response to oxytocin in schizophrenia. PMID:26150070

  10. Erythropoietin pharmacokinetic/pharmacodynamic analysis suggests higher doses in treating neonatal anemia

    PubMed Central

    Neelakantan, Srividya; Widness, John A.; Schmidt, Robert L.; Veng-Pedersen, Peter

    2010-01-01

    Background The establishment of effective treatment of neonatal anemia using recombinant human erythropoietin (r-HuEPO) requires a thorough understanding of the physiology and mechanism of EPO’s pharmacologic effect. The purpose of the present preclinical study in sheep was to elucidate the stimulatory effect of EPO on erythroid progenitors and their differentiation into reticulocytes useful in predicting optimal r-HuEPO dosing. Methods Five young adult sheep each underwent two phlebotomies spaced 4–6 weeks apart in which their hemoglobin levels were reduced from 12 g/dL to 3–4 g/dL. Endogenous EPO levels and reticulocyte counts produced in response to anemia were sampled throughout the study and analyzed using a pharmacokinetic/pharmacodynamic (PK/PD) model. Results The phlebotomy-induced drop in hemoglobin resulted in a increase in EPO levels, which reached a maximum of 764 ± 55 mU/mL (mean ± %CV) in 0.5–2.6 days. The reticulocyte counts increased from baseline values of 76.9 × 103 ± 67/μL to 619 × 103 ± 30/μL in 8 days. The PK/PD analysis indicated an increased maturation time for the reticulocytes (4.88 ± 35 days) and demonstrated that the Emax model for EPO’s activation of the progenitors did not show significant effect saturation at the endogenous EPO levels reached. Conclusions In extrapolating from the animal pilot experiment, the present study provides a case for the use of higher r-HuEPO doses in human studies to determine if higher doses are more effective in treatment of neonatal anemia to reduce, and in some less severe cases, eliminate, the need for blood transfusions. PMID:19371274

  11. Higher anti-depressant dose and major adverse outcomes in moderate chronic kidney disease: a retrospective population-based study

    PubMed Central

    2014-01-01

    Background Many older patients have chronic kidney disease (CKD), and a lower dose of anti-depressants paroxetine, mirtazapine and venlafaxine is recommended in patients with CKD to prevent drug accumulation from reduced elimination. Using information available in large population-based healthcare administrative databases, we conducted this study to determine if ignoring the recommendation and prescribing a higher versus lower dose of anti-depressants associates with a higher risk of adverse events. Methods We conducted a population-based cohort study to describe the 30-day risk of delirium in older adults who initiated a higher vs. lower dose of these three anti-depressants in routine care. We defined delirium using the best proxy available in our data sources - hospitalization with an urgent head computed tomography (CT) scan. We determined if CKD status modified the association between anti-depressant dose and outcome, and examined the secondary outcome of 30 day all-cause mortality. We used multivariable logistic regression analyses to estimate adjusted odds ratios (relative risk (RR)) and 95% confidence intervals. Results We identified adults (mean age 75) in Ontario who started a new study anti-depressant at a higher dose (n = 36,651; 31%) or lower dose (n = 81,160; 69%). Initiating a higher vs. lower dose was not associated with an increased risk of hospitalization with head CT (1.09% vs. 1.27% (adjusted RR 0.90; 95% CI, 0.80 to 1.02), but was associated with a lower risk of all-cause mortality (0.76% vs. 0.97% RR 0.82; 95% CI, 0.71 to 0.95). Neither of these relative risks were modified by the presence of CKD (p = 0.16, 0.68, respectively). Conclusions We did not observe an increase in two adverse outcomes when study anti-depressants were initiated at a higher dose in elderly patients with moderate CKD. Contrary to our hypothesis, the 30-day risk of mortality was lower when a higher versus lower dose of anti-depressant was initiated in these

  12. Are higher doses of proton pump inhibitors better in acute peptic bleeding?

    PubMed

    Villalón, Alejandro; Olmos, Roberto; Rada, Gabriel

    2016-06-24

    Although there is broad consensus about the benefits of proton pump inhibitors in acute upper peptic bleeding, there is still controversy over their optimal dosing. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified six systematic reviews including 27 randomized trials addressing this question. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded high-dose proton pump inhibitors probably result in little or no difference in re-bleeding rate or mortality. The risk/benefit and cost/benefit balance probably favor use of low-doses.

  13. Are higher doses of proton pump inhibitors better in acute peptic bleeding?

    PubMed

    Villalón, Alejandro; Olmos, Roberto; Rada, Gabriel

    2016-01-01

    Although there is broad consensus about the benefits of proton pump inhibitors in acute upper peptic bleeding, there is still controversy over their optimal dosing. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified six systematic reviews including 27 randomized trials addressing this question. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded high-dose proton pump inhibitors probably result in little or no difference in re-bleeding rate or mortality. The risk/benefit and cost/benefit balance probably favor use of low-doses. PMID:27390875

  14. The safety of higher than standard dose of doxylamine-pyridoxine (Diclectin) for nausea and vomiting of pregnancy.

    PubMed

    Atanackovic, G; Navioz, Y; Moretti, M E; Koren, G

    2001-08-01

    A delayed-release combination of doxylamine-pyridoxine (D-P) (Diclectin) is the only approved antiemetic medication for use in pregnancy in Canada. The standard recommended dose is up to 4 tablets a day, regardless of body weight or severity of symptoms. The objective of this study was to determine the incidence of adverse maternal and fetal effects and pregnancy outcome in 225 women taking Diclectin at the recommended (n = 123) or higher than recommended (n = 102) doses. In this observational, prospective study, one-third (33.6%) of women reported having adverse effects (sleepiness, tiredness, and/or drowsiness) temporally related to the medication. There was no association between the dose per kg and rates of reported maternal adverse effects with doses ranging from 0.1 mg/kg to 2.0 mg/kg (1-12 tablets). Nausea and vomiting of pregnancy (NVP) was reported as severe by the majority (75.8%) of women. Mean birth weight (BW) was 3,400 g and gestational age (GA) 39 weeks. Multivariate analysis revealed that only prepregnancy weight and GA predicted lower BW, not the dose of D-P or the severity of NVP. There were two pregnancies with major malformation, a finding that is consistent with the rates of birth defects in the general population. It was concluded that the higher than standard dose of Diclectin, when calculated per kg of body weight, does not affect either the incidence of maternal adverse effects or pregnancy outcome. If needed, Diclectin can be given at doses higher than 4 tablets/day to normalize for body weight or optimize efficacy.

  15. Higher Chest Wall Dose Results in Improved Locoregional Outcome in Patients Receiving Postmastectomy Radiation

    SciTech Connect

    Panoff, Joseph E.; Takita, Cristiane; Hurley, Judith; Reis, Isildinha M.; Zhao, Wei; Rodgers, Steven E.; Gunaseelan, Vijayalakshmi; Wright, Jean L.

    2012-03-01

    Purpose: Randomized trials demonstrating decreased locoregional recurrence (LRR) and improved overall survival (OS) in women receiving postmastectomy radiation therapy (PMRT) used up to 50 Gy to the chest wall (CW), but in practice, many centers boost the CW dose to {>=}60 Gy, despite lack of data supporting this approach. We evaluated the relationship between CW dose and clinical outcome. Methods and Materials: We retrospectively reviewed medical records of 582 consecutively treated patients who received PMRT between January 1999 and December 2009. We collected data on patient, disease, treatment characteristics, and outcomes of LRR, progression-free survival (PFS) and OS. Results: Median follow-up from the date of diagnosis was 44.7 months. The cumulative 5-year incidence of LRR as first site of failure was 6.2%. CW dose for 7% (43 patients) was {<=}50.4 Gy (range, 41.4-50.4 Gy) and 93% received >50.4 Gy (range, 52.4-74.4 Gy). A CW dose of >50.4 Gy vs. {<=}50.4 Gy was associated with lower incidence of LRR, a 60-month rate of 5.7% (95% confidence interval [CI], 3.7-8.2) vs. 12.7% (95% CI, 4.5-25.3; p = 0.054). Multivariate hazard ratio (HR) for LRR controlling for race, receptor status, and stage was 2.62 (95% CI, 1.02-7.13; p = 0.042). All LRR in the low-dose group occurred in patients receiving 50 to 50.4 Gy. Lower CW dose was associated with worse PFS (multivariate HR, 2.73; 95% CI, 1.64-4.56; p < 0.001) and OS (multivariate HR, 3.88; 95% CI, 2.16-6.99; p < 0.001). Conclusions: The addition of a CW boost above 50.4 Gy resulted in improved locoregional control and survival in this cohort patients treated with PMRT for stage II-III breast cancer. The addition of a CW boost to standard-dose PMRT is likely to benefit selected high-risk patients. The optimal technique, target volume, and patient selection criteria are unknown. The use of a CW boost should be studied prospectively, as has been done in the setting of breast conservation.

  16. Distinct Signaling Pathways After Higher or Lower Doses of Radiation in Three Closely Related Human Lymphoblast Cell Lines

    SciTech Connect

    Lu, T.-P.; Lai, L.-C.; Lin, B.-I.; Chen, L.-H.; Hsiao, T.-H.; Liber, Howard L.; Cook, John A.; Mitchell, James B.; Tsai, M.-H.; Chuang, Eric Y.

    2010-01-15

    Purpose: The tumor suppressor p53 plays an essential role in cellular responses to DNA damage caused by ionizing radiation; therefore, this study aims to further explore the role that p53 plays at different doses of radiation. Materials and Methods: The global cellular responses to higher-dose (10 Gy) and lower dose (iso-survival dose, i.e., the respective D0 levels) radiation were analyzed using microarrays in three human lymphoblast cell lines with different p53 status: TK6 (wild-type p53), NH32 (p53-null), and WTK1 (mutant p53). Total RNAs were extracted from cells harvested at 0, 1, 3, 6, 9, and 24 h after higher and lower dose radiation exposures. Template-based clustering, hierarchical clustering, and principle component analysis were applied to examine the transcriptional profiles. Results: Differential expression profiles between 10 Gy and iso-survival radiation in cells with different p53 status were observed. Moreover, distinct gene expression patterns were exhibited among these three cells after 10 Gy radiation treatment, but similar transcriptional responses were observed in TK6 and NH32 cells treated with iso-survival radiation. Conclusions: After 10 Gy radiation exposure, the p53 signaling pathway played an important role in TK6, whereas the NFkB signaling pathway appeared to replace the role of p53 in WTK1. In contrast, after iso-survival radiation treatment, E2F4 seemed to play a dominant role independent of p53 status. This study dissected the impacts of p53, NFkB and E2F4 in response to higher or lower doses of gamma-irradiation.

  17. The H50Q mutation induces a 10-fold decrease in the solubility of α-synuclein.

    PubMed

    Porcari, Riccardo; Proukakis, Christos; Waudby, Christopher A; Bolognesi, Benedetta; Mangione, P Patrizia; Paton, Jack F S; Mullin, Stephen; Cabrita, Lisa D; Penco, Amanda; Relini, Annalisa; Verona, Guglielmo; Vendruscolo, Michele; Stoppini, Monica; Tartaglia, Gian Gaetano; Camilloni, Carlo; Christodoulou, John; Schapira, Anthony H V; Bellotti, Vittorio

    2015-01-23

    The conversion of α-synuclein from its intrinsically disordered monomeric state into the fibrillar cross-β aggregates characteristically present in Lewy bodies is largely unknown. The investigation of α-synuclein variants causative of familial forms of Parkinson disease can provide unique insights into the conditions that promote or inhibit aggregate formation. It has been shown recently that a newly identified pathogenic mutation of α-synuclein, H50Q, aggregates faster than the wild-type. We investigate here its aggregation propensity by using a sequence-based prediction algorithm, NMR chemical shift analysis of secondary structure populations in the monomeric state, and determination of thermodynamic stability of the fibrils. Our data show that the H50Q mutation induces only a small increment in polyproline II structure around the site of the mutation and a slight increase in the overall aggregation propensity. We also find, however, that the H50Q mutation strongly stabilizes α-synuclein fibrils by 5.0 ± 1.0 kJ mol(-1), thus increasing the supersaturation of monomeric α-synuclein within the cell, and strongly favors its aggregation process. We further show that wild-type α-synuclein can decelerate the aggregation kinetics of the H50Q variant in a dose-dependent manner when coaggregating with it. These last findings suggest that the precise balance of α-synuclein synthesized from the wild-type and mutant alleles may influence the natural history and heterogeneous clinical phenotype of Parkinson disease. PMID:25505181

  18. The H50Q Mutation Induces a 10-fold Decrease in the Solubility of α-Synuclein*

    PubMed Central

    Porcari, Riccardo; Proukakis, Christos; Waudby, Christopher A.; Bolognesi, Benedetta; Mangione, P. Patrizia; Paton, Jack F. S.; Mullin, Stephen; Cabrita, Lisa D.; Penco, Amanda; Relini, Annalisa; Verona, Guglielmo; Vendruscolo, Michele; Stoppini, Monica; Tartaglia, Gian Gaetano; Camilloni, Carlo; Christodoulou, John; Schapira, Anthony H. V.; Bellotti, Vittorio

    2015-01-01

    The conversion of α-synuclein from its intrinsically disordered monomeric state into the fibrillar cross-β aggregates characteristically present in Lewy bodies is largely unknown. The investigation of α-synuclein variants causative of familial forms of Parkinson disease can provide unique insights into the conditions that promote or inhibit aggregate formation. It has been shown recently that a newly identified pathogenic mutation of α-synuclein, H50Q, aggregates faster than the wild-type. We investigate here its aggregation propensity by using a sequence-based prediction algorithm, NMR chemical shift analysis of secondary structure populations in the monomeric state, and determination of thermodynamic stability of the fibrils. Our data show that the H50Q mutation induces only a small increment in polyproline II structure around the site of the mutation and a slight increase in the overall aggregation propensity. We also find, however, that the H50Q mutation strongly stabilizes α-synuclein fibrils by 5.0 ± 1.0 kJ mol−1, thus increasing the supersaturation of monomeric α-synuclein within the cell, and strongly favors its aggregation process. We further show that wild-type α-synuclein can decelerate the aggregation kinetics of the H50Q variant in a dose-dependent manner when coaggregating with it. These last findings suggest that the precise balance of α-synuclein synthesized from the wild-type and mutant alleles may influence the natural history and heterogeneous clinical phenotype of Parkinson disease. PMID:25505181

  19. Higher infused lymphocyte dose predicts higher lymphocyte recovery, which in turn, predicts superior overall survival following autologous hematopoietic stem cell transplantation for multiple myeloma.

    PubMed

    Hiwase, Devendra K; Hiwase, Smita; Bailey, Michael; Bollard, Geraldine; Schwarer, Anthony P

    2008-01-01

    Autologous stem cell transplantation (ASCT) is the standard of care for patients with multiple myeloma (MM) younger than 70 years. However, despite this aggressive therapy most patients will still die of progressive disease. Recent reports have suggested that lymphocyte recovery is an important predictor of relapse or progressive disease in a number of hematologic malignancies including MM. We have conducted retrospective analysis of factors that could predict overall (OS) and progression free survival (PFS) in patients with MM who had ASCT. One hundred nineteen patients with multiple myeloma underwent ASCT. The median OS and PFS were 64 and 32 months, respectively. Univariate and multivariate analysis using Cox proportional hazards regression model showed that absolute lymphocyte count on day 30 following ASCT (ALC-30), international staging system (ISS) stage at diagnosis, and age at diagnosis significantly influenced OS and PFS following ASCT. OS (96 versus 48 months, P = .04) and PFS (43 versus 29 months, P = .03) following ASCT were higher in patients with ALC-30 >or=1.0 x 10(9)/L compared to patients ALC-30 <1.0 x 10(9)/L. Higher ALC-60, ALC-100, ALC-180, and ALC-365 did not predict superior OS and PFS. Patients with early-stage disease had significantly higher OS (ISS stages I, II, and III: 96, 53, and 29 months, respectively; P = .0023) and PFS (ISS stages I, II, and III: 55.5, 31, and 12 months, respectively; P = .027) compared to patients with advanced-stage disease at diagnosis. On univariate analysis, the type of initial chemotherapy (melphalan, VAD, PCAB), lymphocyte count on day of leukapheresis, and the lymphocyte dose infused (LY-DO) significantly influenced lymphocyte recovery following ASCT. Patients who received higher lymphocyte dose (LY-DO) >or=0.2 x 10(9)/kg had higher median ALC-15 (0.25 versus 0.19 x 10(9)/L; P = .3), ALC-30 (1.20 versus 0.99 x 10(9)/L; P = .08), ALC-60 (1.90 versus 1.01 x 10(9)/L; P = .013), ALC-100 (1.58 versus 1.03 x 10

  20. Higher initial tacrolimus blood levels and concentration-dose ratios in kidney transplant recipients who develop diabetes mellitus.

    PubMed

    Rodrigo, E; de Cos, M A; Fernández-Fresnedo, G; Sánchez, B; Ruiz, J C; Piñera, C; Palomar, R; Cotorruelo, J G; Gómez-Alamillo, C; de Castro, S Sanz; de Francisco, A L M; Arias, M

    2005-11-01

    Posttransplantation diabetes mellitus (PTDM) is a common complication of kidney transplantation, associated with poorer graft and patient outcomes. Tacrolimus is a strong immunosuppressive drug associated with low acute rejection rates, but a higher risk for PTDM. High trough levels of tacrolimus during the first month after transplantation have been found to be a significant risk factor for the development of PTDM. The aim of this single-center study was to identify the risk factors for the development of PTDM among kidney transplant recipients under tacrolimus therapy. We examined 73 cadaveric kidney transplant recipients receiving tacrolimus between 1994 and 2003. Age, donor and recipient gender, dialysis method, body mass index (BMI), first year weight gain, mismatches, incidence of acute rejection and delayed graft function, hepatitis C serology, first year cumulative steroid dose, first tacrolimus blood level, first tacrolimus blood level <15 ng/mL, and corresponding tacrolimus daily doses and concentration/dose ratios (CDR) were also collected. PTDM was defined as at least 2 fasting blood glucose values > or =126 mg/dL, according to the World Health Organization criteria. Incidence of first year PTDM was 27.4%. Patients with PTDM showed significantly higher age, BMI, first tacrolimus blood level, first tacrolimus CDR, and CDR with tacrolimus blood level <15 ng/mL as well as less 1-year weight gain. After logistic regression, age (relative risk [RR] 1.060, confidence interval [CI] 95%, 1.001-1.122; P = .043) and first tacrolimus blood level (RR 1.154; CI 95%, 1.038-1.283; P = .008) remain significant risk factors for developing PTDM. Older age and initial tacrolimus blood levels were the main risk factors for PTDM among our group of patients. Kidney transplant recipients who develop PTDM maintain a high CDR of tacrolimus.

  1. Morphine with adjuvant ketamine versus higher dose of morphine alone for acute pain: a meta-analysis

    PubMed Central

    Ding, Xibing; Jin, Shuqing; Niu, Xiaoyin; Wang, Tingting; Zhao, Xiang; Ren, Hao; Tong, Yao; Li, Quan

    2014-01-01

    Purpose: Ketamine is currently the N-methyl-D-aspartate receptor channel blocker in clinical use. Morphine in pain management is usually limited by adverse effect such as nausea and vomiting. Adjuvant treatment with ketamine may be value in giving better analgesia with fewer adverse effects. The purpose of this meta-analysis was to evaluate the differences when patients received morphine with adjuvant ketamine (MK) compared with higher dose of morphine (MO) for acute pain. Methods: The PubMed, EMBASE and the Cochrane Library databases were searched (Last search performed on July 1, 2014) by two reviewers independently. Data were extracted independently by the same two individuals who searched the studies. Results: A total of 7 trials involving 492 patients were included in the current analysis. We found pain scores were lower in the MK group compared to the MO group [MD 2.19, 95% CI (1.24, 3.13) P<0.00001]. And more patients in the MO required diclofenac [OR 1.97, 95% CI (1.06, 3.67) P=0.03]. Furthermore, morphine plus ketamine can reduced post-operative nausea and vomiting (PONV) [OR 3.71, 95% CI (2.37, 5.80) P<0.00001]. Importantly, the wakefulness scores for the MK group were consistently and significantly better than those for the MO group [MD -1.53, 95% CI (-2.67, -0.40) P=0.008]. Conclusion: The use of ketamine plus 1/4~2/3 the dose of morphine is better than higher dose of morphine alone in reducing pain scores, and rescuing analgesic requirement. It also improved PONV and wakefulness. PMID:25356103

  2. Healthy birth weight results in higher vitamin A storage in neonate piglets administered high-dose supplements.

    PubMed

    Heying, Emily K; Hovel, Elizabeth; Tanumihardjo, Sherry A

    2015-10-01

    A proposed intervention for newborn infants in countries with suspected vitamin A (VA) deficiency is to administer 50,000 IU retinyl palmitate at birth to reduce mortality risk. However, no studies have investigated birth weight effects. In this study, low birth weight (LBW; <1 kg, n = 18) and healthy birth weight (HBW) piglets (>1.5 kg, n = 18) from VA-depleted sows were dosed with 25,000 or 50,000 IU retinyl palmitate (26.2 or 52.4 µmol retinol equivalents) at birth to compare VA reserves. Blood was collected at varying times (n = 3-5/time/dose), and piglets were killed at 12 or 24 h for blood, liver, kidneys, spleen, lungs, adrenal gland, and intestinal contents. HBW piglets had significantly higher birth, death, and organ weights than LBW (P < 0.0001 for all). HBW and LBW piglets, which received VA, had higher liver and kidney VA concentrations (0.18 ± 0.09, 0.24 ± 0.10 µmol/g liver and 13.4 ± 4.1, 14.2 ± 4.5 nmol/g kidney, respectively) than controls (n = 10) (0.051 ± 0.01 µmol/g liver and 1.01 ± 0.43 nmol/g kidney) (P = 0.0061 and < 0.0001, respectively). Total liver (9.75 ± 5.16 µmol) and kidney retinol (204 ± 79.1 nmol) were higher in HBW than LBW piglets (P < 0.0001). Extrahepatic tissues, except lung, had higher VA concentration than controls (P < 0.0001). Serum retinol and ester concentrations were higher in treated than control piglets (P = 0.0028, P < 0.0001, respectively), and significantly changed during the times sampled (P = 0.022, P = 0.011, respectively). Peak serum retinyl ester concentrations, which occurred at 3 h, were higher in piglets that received 50,000 IU (4.2 ± 4.4 µmol/L) than 25,000 IU (2.7 ± 2.3 µmol/L) (P = 0.031). Regardless of dose amount, HBW piglets stored more supplemental VA than LBW piglets when administered at birth. PMID:25681469

  3. Healthy birth weight results in higher vitamin A storage in neonate piglets administered high-dose supplements

    PubMed Central

    Heying, Emily K; Hovel, Elizabeth

    2015-01-01

    A proposed intervention for newborn infants in countries with suspected vitamin A (VA) deficiency is to administer 50,000 IU retinyl palmitate at birth to reduce mortality risk. However, no studies have investigated birth weight effects. In this study, low birth weight (LBW; <1 kg, n = 18) and healthy birth weight (HBW) piglets (>1.5 kg, n = 18) from VA-depleted sows were dosed with 25,000 or 50,000 IU retinyl palmitate (26.2 or 52.4 µmol retinol equivalents) at birth to compare VA reserves. Blood was collected at varying times (n = 3–5/time/dose), and piglets were killed at 12 or 24 h for blood, liver, kidneys, spleen, lungs, adrenal gland, and intestinal contents. HBW piglets had significantly higher birth, death, and organ weights than LBW (P < 0.0001 for all). HBW and LBW piglets, which received VA, had higher liver and kidney VA concentrations (0.18 ± 0.09, 0.24 ± 0.10 µmol/g liver and 13.4 ± 4.1, 14.2 ± 4.5 nmol/g kidney, respectively) than controls (n = 10) (0.051 ± 0.01 µmol/g liver and 1.01 ± 0.43 nmol/g kidney) (P = 0.0061 and < 0.0001, respectively). Total liver (9.75 ± 5.16 µmol) and kidney retinol (204 ± 79.1 nmol) were higher in HBW than LBW piglets (P < 0.0001). Extrahepatic tissues, except lung, had higher VA concentration than controls (P < 0.0001). Serum retinol and ester concentrations were higher in treated than control piglets (P = 0.0028, P < 0.0001, respectively), and significantly changed during the times sampled (P = 0.022, P = 0.011, respectively). Peak serum retinyl ester concentrations, which occurred at 3 h, were higher in piglets that received 50,000 IU (4.2 ± 4.4 µmol/L) than 25,000 IU (2.7 ± 2.3 µmol/L) (P = 0.031). Regardless of dose amount, HBW piglets stored more supplemental VA than LBW piglets when administered at birth. PMID:25681469

  4. Effects of a higher dose of near-infrared light on clinical signs and neuroprotection in a monkey model of Parkinson's disease.

    PubMed

    Moro, Cécile; El Massri, Nabil; Darlot, Fannie; Torres, Napoleon; Chabrol, Claude; Agay, Diane; Auboiroux, Vincent; Johnstone, Daniel M; Stone, Jonathan; Mitrofanis, John; Benabid, Alim-Louis

    2016-10-01

    We have reported previously that intracranial application of near-infrared light (NIr) - when delivered at the lower doses of 25J and 35J - reduces clinical signs and offers neuroprotection in a subacute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of Parkinson's disease. In this study, we explored whether a higher NIr dose (125J) generated beneficial effects in the same MPTP monkey model (n=15). We implanted an NIr (670nm) optical fibre device within a midline region of the midbrain in macaque monkeys, close to the substantia nigra of both sides. MPTP injections (1.8-2.1mg/kg) were made over a five day period, during which time the NIr device was turned on and left on continuously throughout the ensuing three week survival period. Monkeys were evaluated clinically and their brains processed for immunohistochemistry and stereology. Our results showed that the higher NIr dose did not have any toxic impact on cells at the midbrain implant site. Further, this NIr dose resulted in a higher number of nigral tyrosine hydroxylase immunoreactive cells when compared to the MPTP group. However, the higher NIr dose monkeys showed little evidence for an increase in mean clinical score, number of nigral Nissl-stained cells and density of striatal tyrosine hydroxylase terminations. In summary, the higher NIr dose of 125J was not as beneficial to MPTP-treated monkeys as compared to the lower doses of 25J and 35J, boding well for strategies of NIr dose delivery and device energy consumption in a future clinical trial. PMID:27396907

  5. [The dynamics of the rats higher nervous activity disturbances after total influence of electrons and gamma-rays in doses 5-100 Gy].

    PubMed

    Shtemberg, A S

    2008-01-01

    The dynamics of using of stabilized motor defensive conditioned reflex of active avoidance in "shuttle-box" in rats after total influence of high energy electrons and of gamma-rays in doses 5-100 Gy were investigated. The quality structure of higher nervous activity disturbances after the influence of these kinds of ionizing radiation was identical. Therefore the tendency to disturbances aggravating after the electron radiation influence in the periods of the initial depression and of relatively normalization was revealed, especially after the irradiation in dose 50 Gy. The effective compensation of the functional disturbances in the central nervous system at the first 5-10 min after irradiation was after influence of electron radiation in doses about 30 Gy and after the influence of gamma-radiation in doses about 50 Gy. The irradiation of rats in doses 10 Gy and 5 Gy caused qualitative different dynamics of radiation disturbances in rats higher nervous activity. The differences in rats higher nervous activity after influence of electron and of gamma-radiation in these doses did not manifest distinctly.

  6. Specific binding of gibberellic acid by cytokinin-specific binding proteins: a new aspect of plant hormone-binding proteins with the PR-10 fold.

    PubMed

    Ruszkowski, Milosz; Sliwiak, Joanna; Ciesielska, Agnieszka; Barciszewski, Jakub; Sikorski, Michal; Jaskolski, Mariusz

    2014-07-01

    Pathogenesis-related proteins of class 10 (PR-10) are a family of plant proteins with the same fold characterized by a large hydrophobic cavity that allows them to bind various ligands, such as phytohormones. A subfamily with only ~20% sequence identity but with a conserved canonical PR-10 fold have previously been recognized as Cytokinin-Specific Binding Proteins (CSBPs), although structurally the binding mode of trans-zeatin (a cytokinin phytohormone) was found to be quite diversified. Here, it is shown that two CSBP orthologues from Medicago truncatula and Vigna radiata bind gibberellic acid (GA3), which is an entirely different phytohormone, in a conserved and highly specific manner. In both cases a single GA3 molecule is found in the internal cavity of the protein. The structural data derived from high-resolution crystal structures are corroborated by isothermal titration calorimetry (ITC), which reveals a much stronger interaction with GA3 than with trans-zeatin and pH dependence of the binding profile. As a conclusion, it is postulated that the CSBP subfamily of plant PR-10 proteins should be more properly linked with general phytohormone-binding properties and termed phytohormone-binding proteins (PhBP).

  7. The copper-mobilizing-potential of dissolved organic matter in soils varies 10-fold depending on soil incubation and extraction procedures.

    PubMed

    Amery, Fien; Degryse, Fien; Degeling, Wim; Smolders, Erik; Merckx, Roel

    2007-04-01

    Copper is mobilized in soil by dissolved organic matter (DOM) but the role of DOM quality in this process is unclear. A one-step resin-exchange method was developed to measure the Cu-Mobilizing-Potential (CuMP) of DOM at pCu 11.3 and pH 7.0, representing background values. The CuMP of DOM was measured in soil solutions of 13 uncontaminated soils with different DOM extraction methods. The CuMP, expressed per unit dissolved organic carbon (DOC), varied 10-fold and followed the order water extracts > 0.01 M CaCl2 extracts > pore water. Soil solutions, obtained from soils that were stored air-dry for a long time or were subjected to drying-wetting cycles, had elevated DOC concentration, but the DOM had a low CuMP. Prolonged soil incubations decreased the DOC concentration and increased the CuMP, suggesting that most of the initially elevated DOM is less humified and has lower Cu affinity than DOM remaining after incubation. A significant positive correlation between the specific UV-absorption of DOM (indicating aromaticity) and CuMP was found for all DOM samples (R(2) = 0.58). It is concluded that the DOC concentration in soil is an insufficient predictor for the Cu mobilization and that DOM samples isolated from air-dried soils are distinct from those of soils kept moist. PMID:17438775

  8. Higher Dose of Mycophenolate Mofetil Reduces Acute Graft-Versus-Host Disease in Reduced Intensity Conditioning Double Umbilical Cord Blood Transplantation

    PubMed Central

    Bejanyan, Nelli; Rogosheske, John; DeFor, Todd; Lazaryan, Aleksandr; Esbaum, Kelli; Holtan, Shernan; Arora, Mukta; MacMillan, Margaret L.; Weisdorf, Daniel; Jacobson, Pamala; Wagner, John; Brunstein, Claudio G.

    2016-01-01

    Mycophenolate mofetil (MMF) is frequently used in hematopoietic cell transplantation (HCT) for graft-versus-host disease (GVHD) prophylaxis and to facilitate engraftment. We previously reported that a higher level of mycophenolic acid can be achieved with an MMF dose of 3 g/day as compared to 2g/day. Here, we retrospectively compared clinical outcomes of reduced intensity conditioning (RIC) double umbilical cord blood (dUCB) HCT recipients receiving cyclosporine A with MMF 2g (n=93) vs. 3g (n=175) daily. Multiple regression analysis adjusted for ATG in the conditioning revealed that MMF 3g/day led to a 49% relative risk reduction in grade II–IV acute GVHD rate (RR=0.51, 95%CI 0.36–0.72; p<0.01). However, the higher MMF dose was not protective for chronic GVHD. Additionally, MMF dose was not an independent predictor of neutrophil engraftment, treatment-related mortality at 6 months, or 2-year post-transplant disease relapse, disease-free survival, or overall survival. Higher MMF dose did not increase risk of infectious complications and infection-related mortality was similar for both MMF doses. Our data indicate that MMF 3g/day reduces the risk of acute GVHD without affecting other clinical outcomes and should be used for GVHD prophylaxis after RIC dUCBT. PMID:25655791

  9. Higher-Than-Conventional Radiation Doses in Localized Prostate Cancer Treatment: A Meta-analysis of Randomized, Controlled Trials

    SciTech Connect

    Viani, Gustavo Arruda Stefano, Eduardo Jose; Afonso, Sergio Luis

    2009-08-01

    Purpose: To determine in a meta-analysis whether the outcomes in men with localized prostate cancer treated with high-dose radiotherapy (HDRT) are better than those in men treated with conventional-dose radiotherapy (CDRT), by quantifying the effect of the total dose of radiotherapy on biochemical control (BC). Methods and Materials: The MEDLINE, EMBASE, CANCERLIT, and Cochrane Library databases, as well as the proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing HDRT with CDRT for localized prostate cancer. To evaluate the dose-response relationship, we conducted a meta-regression analysis of BC ratios by means of weighted linear regression. Results: Seven RCTs with a total patient population of 2812 were identified that met the study criteria. Pooled results from these RCTs showed a significant reduction in the incidence of biochemical failure in those patients with prostate cancer treated with HDRT (p < 0.0001). However, there was no difference in the mortality rate (p = 0.38) and specific prostate cancer mortality rates (p = 0.45) between the groups receiving HDRT and CDRT. However, there were more cases of late Grade >2 gastrointestinal toxicity after HDRT than after CDRT. In the subgroup analysis, patients classified as being at low (p = 0.007), intermediate (p < 0.0001), and high risk (p < 0.0001) of biochemical failure all showed a benefit from HDRT. The meta-regression analysis also detected a linear correlation between the total dose of radiotherapy and biochemical failure (BC = -67.3 + [1.8 x radiotherapy total dose in Gy]; p = 0.04). Conclusions: Our meta-analysis showed that HDRT is superior to CDRT in preventing biochemical failure in low-, intermediate-, and high-risk prostate cancer patients, suggesting that this should be offered as a treatment for all patients, regardless of their risk status.

  10. Success of short-term, higher-dose imatinib mesylate to induce clinical response in FIP1L1-PDGFRalpha-negative hypereosinophilic syndrome.

    PubMed

    Butterfield, Joseph H

    2009-08-01

    Presence of the oncogenic mutation FIP1L1-PDGFRalpha in hypereosinophilic patients is predictive of hematologic response to imatinib mesylate. However, most patients with hypereosinophilic syndrome (HES) do not have this mutation and have not responded to imatinib doses traditionally successful in patients who test positive for FIP1L1-PDGFRalpha. A patient with FIP1L1-PDGFRalpha-negative HES who had intolerance of interferon alpha-2b and hydroxyurea was treated with escalating doses of imatinib. At 800 mg of imatinib daily, eosinophilia was controlled, allowing prednisone tapering and control of clinical and laboratory-detected abnormalities. HES patients who test negative for FIP1L1-PDGFRalpha may benefit from a trial of higher-dose imatinib.

  11. Prevention of recurrence of atypical hemolytic uremic syndrome post renal transplant with the use of higher-dose eculizumab
.

    PubMed

    Riddell, Amy; Goodship, Tim; Bingham, Coralie

    2016-10-01

    Eculizumab, a terminal complement inhibitor, has recently been used successfully to both prevent and treat the recurrence of atypical hemolytic uremic syndrome (aHUS) post renal transplantation. We describe a case that highlights the need to monitor the effects of eculizumab on the complement system and in this case alter the dosage. Despite taking the standard recommended dose of eculizumab for an adult, this aHUS patient developed a low-grade thrombotic microangiopathy on biopsy within months of renal transplantation. Complement assays (trough CH50) showed small amounts of residual terminal pathway activity suggesting inadequate complement blockade on 1,200 mg eculizumab every 2 weeks. Following an increase in the dose of eculizumab to 1,500 mg every 2 weeks, lactate dehydrogenase (LDH), proteinuria, and creatinine decreased, and CH50 assay showed 0%. This case emphasizes the need to monitor clinical parameters and complement activity to ensure that adequate therapeutic blockade is achieved.
.

  12. New developed DR detector performs radiographs of hand, pelvic and premature chest anatomies at a lower radiation dose and/or a higher image quality.

    PubMed

    Precht, Helle; Tingberg, Anders; Waaler, Dag; Outzen, Claus Bjørn

    2014-02-01

    A newly developed Digital Radiography (DR) detector has smaller pixel size and higher fill factor than earlier detector models. These technical advantages should theoretically lead to higher sensitivity and higher spatial resolution, thus making dose reduction possible without scarifying image quality compared to previous DR detector versions. To examine whether the newly developed Canon CXDI-70C DR detector provides an improved image quality and/or allows for dose reductions in hand and pelvic bone examinations as well as premature chest examinations, compared to the previous (CXDI-55C) DR detector version. A total of 450 images of a technical Contrast-Detail phantom were imaged on a DR system employing various kVp and mAs settings, providing an objective image quality assessment. In addition, 450 images of anthropomorphic phantoms were taken and analyzed by three specialized radiologists using Visual Grading Analysis (VGA). The results from the technical phantom studies showed that the image quality expressed as IQFINV values was on average approximately 45 % higher with the CXDI-70C detector compared to the CXDI-55C detector. Consistently, the VGA results from the anatomical phantom studies indicated that by using the CXDI-70C detector, diagnostic image quality could be maintained at a dose reduction of in average 30 %, depending on anatomy and kVp level. This indicates that the CXDI-70C detector is significantly more sensitive than the previous model, and supports a better clinical image quality. By using the newly developed DR detector a significant dose reduction is possible while maintaining image quality.

  13. Effect of rosiglitazone and ramipril on macrovasculopathy in patients with type 2 diabetes: needs longer treatment and/or higher doses?

    PubMed Central

    Rahman, Sayeeda; Ismail, Aziz Al-Shafi; Ismail, Shaiful Bhari; Naing, Nyi Nyi; Rahman, Abdul Rashid Abdul

    2010-01-01

    Introduction The aim of the study is to investigate whether standard doses of rosiglitazone (4 mg/daily) and ramipril (5 mg/daily) can reverse pre-clinical macrovasculopathy in newly diagnosed never treated type 2 diabetes (T2DM) patients. Methods In this randomized, double-blind, placebo-controlled study, 33 T2DM patients were randomized to rosiglitazone (4 mg/daily) or ramipril (5 mg/daily) or placebo for 1 year. Hemodynamic variables were measured at 3 treatment phases and pulse wave velocity (PWV) and augmentation index (AI) were measured throughout the treatment period. Result In diabetic patients, PWV (P = 0.037) and AI (P = 0.005) with ramipril and AI (P < 0.001) with rosiglitazone were significantly reduced during overall treatment period from the baseline; however, these differences were not significant in comparison to placebo. Discussion and conclusion The present study showed that treatment with standard doses of rosiglitazone and ramipril are not adequate to reverse pre-clinical vasculopathy in T2DM. The lack of benefit in newly diagnosed T2DM may be because of the relatively short-term intervention and/or the use of lower doses of rosiglitazone/ramipril. Further trials are needed for a longer period of time, possibly with higher doses, to show whether rosiglitazone/ramipril can reverse pre-clinical vasculopathy in T2DM (ClinicalTrials.gov number, NCT00489229). PMID:22291490

  14. Significance of higher drug concentration in erythrocytes of mice infected with Schistosoma japonicum and treated orally with mefloquine at single doses.

    PubMed

    Tao, Yi; Xue, Jian; Jiang, Bin; Zhang, Hao-Bing; Xiao, Shu-Hua

    2015-12-01

    The purpose of the present study is to understand the pharmacokinetic feature of mefloquine measured by erythrocytes and plasma in Schistosoma japonicum (S. j.)-infected mice and non-infected mice after oral administration of the drug at single doses. A high-performance liquid chromatography (HPLC) method was used to measure the plasma and erythrocyte concentrations of mefloquine at varying intervals posttreatment. Our results demonstrated that in non-infected mice treated orally with mefloquine at an ineffective dose of 50 mg/kg or effective dose of 200 mg/kg for 2-72 h, the erythrocyte-to-plasma ratios of mefloquine were 5.8-11.2 or 2-14.2. On the other hand, in S. j.-infected mice treated with the same single doses of the drug, the erythrocyte and plasma drug concentration ratios were 3.1-4.6 or 2.9-8.5, manifesting that either in infected mice or in non-infected mice that received oral mefloquine resulted in higher concentration of mefloquine in erythrocytes than that in plasma. Unexpectedly, under oral administration of mefloquine at a higher single dose of 200 mg/kg, the pharmacokinetic parameter C max values for plasma from S. j.-infected and non-infected mice were 1.6 ± 0.3 and 2.0 ± 0.4 μg/mL, respectively, which were below the determined in vitro LC50 (50 % lethal concentration) value of 4.93 μg/mL. Therefore, the plasma concentration of mefloquine may display a little effect against schistosomes during the treatment. Although the values of T 1/2 and AUC0-∞ for erythrocytes were significantly longer and higher in infected mice than those of corresponding non-infect mice that received the same single mefloqine dose of 50 mg/kg, the C max value was only 2.6 ± 0.4 μg/mL lower than the determined in vitro LC50, which may explain why this low single dose is ineffective against schistosomes in vivo. After administration of higher mefloquine dose of 200 mg/kg, the C max value for erythrocytes in infected mice was 30 % (7.4 ± 0

  15. Geometrical Sparing Factors for the Rectum and Bladder in the Prediction of Grade 2 and Higher Complications After High-Dose-Rate Brachytherapy for Cervical Cancer

    SciTech Connect

    Chen, S.-W.; Liang, J.-A.; Hung, Y.-C.; Yeh, L.-S.; Chang, W.-C.; Yang, S.-N.; Lin, F.-J.

    2009-12-01

    Purpose: This study aimed to assess the predictive values of geometrical sparing factors for the rectum and bladder in high-dose-rate intracavitary brachytherapy (HDRICB) for Grade 2 and higher late sequelae in patients with cervical cancer. Methods: A total of 392 patients were enrolled in this study. They were treated with external beam radiotherapy to the pelvis, after which HDRICB was performed using Ir-192 remote after-loading at 1-week intervals for three or four sessions. The geometrical sparing factor (GSF) was defined as the average of the ratios between the reference doses and the Point A dose. Results: A total of 46 patients (11.7%) had Grade 2 or higher late rectal complications (36 Grade 2, 9 Grade 3, and 1 Grade 4). In all, 32 patients (8.2%) had Grade 2 or higher late bladder complications (14 Grade 2, 16 Grade 3, and 2 Grade 4). Multivariate analysis demonstrated a high risk of rectal sequelae in patients who developed bladder complications (p = 0.0004, hazard ratio 3.54) and had a rectal GSF greater than 0.7 (p = 0.01, hazard ratio 1.99). The high risk factors for bladder complications were development of rectal complications (p = 0.0004, hazard ratio 3.74), concurrent chemotherapy (p = 0.0001, relative risk 3.94), and a bladder GSF greater than 0.9 (p = 0.01, hazard ratio, 2.53). Conclusion: This study demonstrates the predictive value of GSFs in HDRICB for cervical cancer. Patients with rectal GSFs greater than 0.7 or bladder GSFs greater than 0.9 are at risk for Grade 2 and higher late sequelae.

  16. Long-Term Results of Fixed High-Dose I-131 Treatment for Toxic Nodular Goiter: Higher Euthyroidism Rates in Geriatric Patients

    PubMed Central

    Aktaş, Gül Ege; Turoğlu, Halil Turgut; Erdil, Tanju Yusuf; İnanır, Sabahat; Dede, Fuat

    2015-01-01

    Objective: Geriatric patient population has special importance due to particular challenges. In addition to the increase in incidence of toxic nodular goiter (TNG) with age, it has a high incidence in the regions of low-medium iodine intake such as in our country. The aim of this study was to evaluate the overall outcome of high fixed dose radioiodine (RAI) therapy, and investigate the particular differences in the geriatric patient population. Methods: One hundred and three TNG patients treated with high dose I-131 (370-740 MBq) were retrospectively reviewed. The baseline characteristics; age, gender, scintigraphic patterns and thyroid function tests before and after treatment, as well as follow-up, duration of antithyroid drug (ATD) medication and achievement of euthyroid or hypothyroid state were evaluated. The patient population was divided into two groups as those=>65 years and those who were younger, in order to assess the effect of age. Results: Treatment success was 90% with single dose RAI therapy. Hyperthyroidism was treated in 7±7, 2 months after RAI administration. At the end of the first year, overall hypothyroidism rate was 30% and euthyroid state was achieved in 70% of patients. Age was found to be the only statistically significant variable effecting outcome. A higher ratio of euthyroidism was achieved in the geriatric patient population. Conclusion: High fixed dose I-131 treatment should be preferred in geriatric TNG patients in order to treat persistent hyperthyroidism rapidly. The result of this study suggests that high fixed dose RAI therapy is a successful modality in treating TNG, and high rates of euthyroidism can be achieved in geriatric patients. PMID:27529883

  17. Dose calculation for photon-emitting brachytherapy sources with average energy higher than 50 keV: Report of the AAPM and ESTRO

    SciTech Connect

    Perez-Calatayud, Jose; Ballester, Facundo; Das, Rupak K.; DeWerd, Larry A.; Ibbott, Geoffrey S.; Meigooni, Ali S.; Ouhib, Zoubir; Rivard, Mark J.; Sloboda, Ron S.; Williamson, Jeffrey F.

    2012-05-15

    Purpose: Recommendations of the American Association of Physicists in Medicine (AAPM) and the European Society for Radiotherapy and Oncology (ESTRO) on dose calculations for high-energy (average energy higher than 50 keV) photon-emitting brachytherapy sources are presented, including the physical characteristics of specific {sup 192}Ir, {sup 137}Cs, and {sup 60}Co source models. Methods: This report has been prepared by the High Energy Brachytherapy Source Dosimetry (HEBD) Working Group. This report includes considerations in the application of the TG-43U1 formalism to high-energy photon-emitting sources with particular attention to phantom size effects, interpolation accuracy dependence on dose calculation grid size, and dosimetry parameter dependence on source active length. Results: Consensus datasets for commercially available high-energy photon sources are provided, along with recommended methods for evaluating these datasets. Recommendations on dosimetry characterization methods, mainly using experimental procedures and Monte Carlo, are established and discussed. Also included are methodological recommendations on detector choice, detector energy response characterization and phantom materials, and measurement specification methodology. Uncertainty analyses are discussed and recommendations for high-energy sources without consensus datasets are given. Conclusions: Recommended consensus datasets for high-energy sources have been derived for sources that were commercially available as of January 2010. Data are presented according to the AAPM TG-43U1 formalism, with modified interpolation and extrapolation techniques of the AAPM TG-43U1S1 report for the 2D anisotropy function and radial dose function.

  18. Fixed dose of long-acting erythropoietic stimulating agents at higher frequency improves appetite, reduces inflammation and corrects anaemia in patients on haemodialysis.

    PubMed

    Liu, Wen-Sheng; Chu, Da-Chen; Chan, Hsiang-Lin; Li, Szu-Yuan; Liu, Chih-Kuang; Yang, Chih-Yu; Chen, Yu-Wei; Lee, Pui-Ching; Lai, Yen-Ting; Lin, Chih-Ching

    2016-10-01

    Anaemia is an important issue in patients undergoing haemodialysis. We aimed to identify a better dosing schedule of a fixed monthly dose of continuous erythropoietin receptor activator (CERA) in patients with chronic kidney disease (CKD) on haemodialysis. The CERA dosing schedule included 100 μg once monthly for 2 months, 50 μg twice monthly for 2 months and then 100 μg once monthly for two months. The effectiveness was determined by comparing haematocrit, nutritional status (serum protein and albumin) and inflammatory markers (tumour necrosis factor (TNF)-α, interleukin (IL)-1, IL-6 and Hepcidin) at the beginning of the study with those at the end of the study. Forty-seven out of 67 patients completed the trial. At the end, haematocrit was significantly higher (34.51 vs 33.22%, P=.004), levels of inflammatory markers were significantly lower (TNF-α (30.71 vs 35.67 ng/mL, P=.007), IL-6 (5.12 vs 7.95 ng/mL, P=.033), hepcidin (60.39 vs 74.39 ng/mL, P=.002)), blood glucose levels were significantly lower (112.40 vs 139.02 mg/dL, P=.003) and albumin was significantly higher (4.11 vs 3.98, P=.001). Patients with a better than average response had a lower initial number of red blood cells (3.3 vs 3.6 × 10(6) /mm(3) , P=.025) and a lower IL-1 (3.8 vs 12.9 ng/mL, P=.01). They also had significantly lower blood glucose levels at the end. (91.3 vs 124.0 mg/dL, P=.03). We demonstrate that a fixed monthly dose of CERA at a twice monthly dosing schedule improves nutrition, reduces the inflammation and corrects anaemia in patients on haemodialysis. This finding may provide a new strategy for treating CKD-related anaemia.

  19. Enhancement of transformation rates in higher plants by low-dose irradiation: Are DNA repair systems involved in the incorporation of exogenous DNA into the plant genome?

    PubMed

    Köhler, F; Cardon, G; Pöhlman, M; Gill, R; Schieder, O

    1989-02-01

    Irradiation (X-ray; 5-15 Gy) of protoplasts treated with plasmid-DNA and PEG yielded higher transformation rates in comparison to non-irradiated protoplasts transformed by the same method. This could be demonstrated for four plant species. The irradiation doses used did not affect the total number of colonies regenerated without selection pressure, but resulted in 3-6-fold enhancement of hygromycin- or kanamycin-resistant colonies. Plant regeneration frequencies of transformed colonies derived from irradiated and non-irradiated protoplasts were similar in tobacco as well as in Petunia. Higher integration rates of foreign DNA as a consequence of an increased recombination machinery in irradiated cells may be responsible for the enhancement of the number of stably transformed colonies.

  20. Evaluating higher doses of Shunthi - Guduchi formulations for safety in treatment of osteoarthritis knees: A Government of India NMITLI arthritis project

    PubMed Central

    Chopra, Arvind; Saluja, Manjit; Tillu, Girish; Venugopalan, Anuradha; Narsimulu, Gumdal; Sarmukaddam, Sanjeev; Patwardhan, Bhushan

    2012-01-01

    Background: Results of an exploratory trial suggested activity trends of Zingiber officinale-Tinopsora cordifolia (platform combination)-based formulations in the treatment of Osteoarthritis (OA) Knees. These formulations were “platform combination+Withania somnifera+Tribulus terrestris” (formulation B) and “platform combination+Emblica officinale” (formulation C). This paper reports safety of these formulations when used in higher doses (1.5–2 times) along with Sallaki Guggul and Bhallataka Parpati (a Semecarpus anacardium preparation). Materials and Methods: Ninety-two patients with symptomatic OA knees were enrolled in a 6 weeks investigator blind, randomized parallel efficacy 4-arm multicenter drug trial. The 4 arms were (I) formulation B, 2 t.i.d.; (II) formulation B, 2 q.i.d.; (III) platform combination+Sallaki Guggul; (IV) Bhallataka Parpati+formulation C. A detailed enquiry was carried out for adverse events (AE) and drug toxicity as per a priori check list and volunteered information. Laboratory evaluation included detailed hematology and metabolic parameters. Patients were examined at baseline, first and fourth weeks, and on completion. Standard statistical program (SPSS version 12.5) was used for analysis. Results: None of the patients reported serious AE or withdrew due to any drug-related toxicity. Mild gut–related (mostly epigastric burning) AE was reported. A mild increase in liver enzymes [serum glutamic pyruvate transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT)] without any other hepatic abnormality was reported in 2 patients (group IV). Other laboratory parameters remained normal. The mean improvement in active pain visual analog scale (1.4, CI 0.5–2.22), WOMAC (functional activity questionnaire) pain score (1.37, CI 0.22–2.5), and urinary C-TAX (cartilage collagen breakdown product) assay was maximum (NS) in group IV. Lower dose group I showed numerically superior improvement compared with higher dose group II

  1. Fixed-ratio schedules of cocaine self-administration in rhesus monkeys: joint control of responding by past and upcoming doses.

    PubMed

    Galuska, Chad M; Wade-Galuska, Tammy; Woods, James H; Winger, Gail

    2007-03-01

    By manipulating a signaled upcoming cocaine dose, we investigated how the dose just received and the upcoming dose jointly controlled cocaine self-administration. Three rhesus monkeys self-administered cocaine according to a multiple schedule differing in dose following completion of a fixed-ratio response requirement. The larger dose (0.03 or 0.056 mg/kg) was 10-fold higher than the smaller dose (0.003 or 0.0056 mg/kg). Following each infusion, there was an equal probability that the next dose would be large or small. This resulted in four types of signaled transitions: from a small dose to a small dose, small to large, large to large, and large to small. Across conditions the response requirement was increased. At lower ratios, pauses were brief and run rates were controlled by the upcoming dose. At larger ratios, pauses were pronounced, and run rates suppressed, in transitions from a large to a small dose. The behavioral disruption engendered by this transition occurred with both dose combinations. The results suggest that negative discriminable shifts in drug availability disrupt ongoing responding. PMID:17351424

  2. Effect of granulocyte colony-stimulating factor priming combined with low-dose cytarabine and homoharringtonine in higher risk myelodysplastic syndrome patients.

    PubMed

    Wang, Fang-Xia; Zhang, Wang-Gang; He, Ai-Li; Cao, Xin-Mei; Chen, Yin-Xia; Zhao, Wan-Hong; Yang, Yun; Wang, Jian-Li; Zhang, Peng-Yu; Gu, Liu-Fang

    2016-09-01

    As sensitization of leukemia cells with granulocyte colony-stimulating factor (G-CSF) can enhance the cytotoxicity of chemotherapy in myeloid malignancies, a pilot study was conducted in order to evaluate the effect of G-CSF priming combined with low-dose chemotherapy in patients with higher risk myelodysplastic syndrome (MDS). The regimen, G-HA, consisted of cytarabine (Ara-C) 7.5mg/m(2)/12h by subcutaneous injection, days 1-14, homoharringtonine (HHT) 1.5mg/m(2)/day by intravenous continuous infusion, days 1-14, and G-CSF 150mg/m(2)/day by subcutaneous injection, days 0-14. 56 patients were enrolled, 34 patients (61%, 95% confidence interval: 51.44-70.56%) achieved complete remission (CR). Median duration of neutropenia was 7days (ranging from 2 to 16days). Grade 1-2 nonhematologic toxicities were documented, including nausea and vomiting (5%), liver function abnormality (5%), and heart function abnormality (2%). No central nervous system toxicity was found. Mortality within the first 4 weeks was 4%. The G-HA regimen is effective in remission induction for higher risk MDS patients and well tolerated due to the acceptable toxicity in maintenance therapy in the patients who cannot undergo Hematopoietic cell transplantation (HCT). PMID:27497340

  3. Radiotherapy Doses of 80 Gy and Higher Are Associated With Lower Mortality in Men With Gleason Score 8 to 10 Prostate Cancer

    SciTech Connect

    Pahlajani, Niraj; Ruth, Karen J.; Buyyounouski, Mark K.; Chen, David Y.T.; Horwitz, Eric M.; Hanks, Gerald E.; Price, Robert A.; Pollack, Alan

    2012-04-01

    Purpose: Men with Gleason score (GS) 8-10 prostate cancer (PCa) are assumed to have a high risk of micrometastatic disease at presentation. However, local failure is also a major problem. We sought to establish the importance of more aggressive local radiotherapy (RT) to {>=}80 Gy. Methods and Materials: There were 226 men treated consecutively with RT {+-} ADT from 1988 to 2002 for GS 8-10 PCa. Conventional, three-dimensional conformal or intensity-modulated (IM) RT was used. Radiation dose was divided into three groups: (1) <75 Gy (n = 50); (2) 75-79.9 Gy (n = 60); or (3) {>=}80 Gy (n = 116). The endpoints examined included biochemical failure (BF; nadir + 2 definition), distant metastasis (DM), cause-specific mortality, and overall mortality (OM). Results: Median follow-up was 66, 71, and 58 months for Groups 1, 2, and 3. On Fine and Gray's competing risk regression analysis, significant predictors of reduced BF were RT dose {>=}80 Gy (p = 0.011) and androgen deprivation therapy duration {>=}24 months (p = 0.033). In a similar model of DM, only RT dose {>=}80 Gy was significant (p = 0.007). On Cox regression analysis, significant predictors of reduced OM were RT dose {>=}80 Gy (p = 0.035) and T category (T3/4 vs. T1, p = 0.041). Dose was not a significant determinant of cause-specific mortality. Results for RT dose were similar in a model with RT dose and ADT duration as continuous variables. Conclusion: The results indicate that RT dose escalation to {>=}80 Gy is associated with lower risks of BF, DM, and OM in men with GS 8-10 PCa, independently of androgen deprivation therapy.

  4. The appropriate dose of angiotensin‐converting‐enzyme inhibitors or angiotensin receptor blockers in patients with dilated cardiomyopathy. The higher, the better?

    PubMed Central

    Konishi, Masaaki; von Haehling, Stephan

    2015-01-01

    Abstract Heart failure is a major public issue, and dilated cardiomyopathy (DCM) is one of the common etiologies of heart failure. DCM is generally progressive, and some patients with DCM need heart transplant despite optimal medical and mechanical therapy. Current guidelines recommend inhibitors of renin–angiotensin–aldosterone system, namely angiotensin‐converting‐enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB), and mineralocorticoid receptor antagonist as well as beta‐blockers for the medical treatment of heart failure with reduced ejection fraction, including DCM. Furthermore, because they have beneficial effects on the outcome of heart failure in a dose‐related fashion, they should be titrated to the target dose. In clinical practice, the underuse and under‐dose of these agents matter; however, the efficacy and safety of supramaximal dose of ACE inhibitor or ARB have never been investigated in the patients with DCM. In this issue of ESC Heart Failure, it is demonstrated that benazepril or valsartan at supramaximal dose improved left ventricular function and reduced cardiovascular events compared with each drug at low dose, respectively. In this editorial, the current evidence concerning the use of ACE inhibitor or ARB in patients with HF and future prospective will be discussed.

  5. Successful Use of Higher-Dose Etanercept for Multirefractory Systemic Flare of Adult-Onset Still's Disease with Liver Failure with No Response to Tocilizumab Therapy

    PubMed Central

    Tamechika, Shinya; Iwagaitsu, Shiho; Maeda, Shinji; Togawa, Hiroyuki

    2013-01-01

    A 21-year-old woman with refractory systemic flare of adult-onset Still's disease with liver failure despite high-dose corticosteroids, cyclosporine, tacrolimus, and tocilizumab, was successfully treated with additional use of etanercept. Etanercept at a dose of 50 mg weekly was partially effective but could not reduce the dose of concomitant betamethasone from 5 mg/day. Etanercept at a dose of 75 mg weekly could lead her to clinical remission and enabled successful tapering off the corticosteroids and discontinuation of etanercept. Normalization of serum C-reactive protein and interleukin 6 and persistent elevation of serum tumor necrosis factor α under the treatment with high-dose corticosteroids and immunosuppressants suggest that tumor necrosis factor α was more deeply involved than at least interleukin 6 in the pathogenesis of refractoriness of the disease in this patient, and these findings might be indicative of potential efficacy for adjunctive use of a tumor necrosis factor inhibitor rather than an interleukin 6 inhibitor. PMID:24455384

  6. Pharmacological rationale for the treatment of chronic urticaria with second-generation non-sedating antihistamines at higher-than-standard doses.

    PubMed

    Zuberbier, T

    2012-01-01

    Chronic urticaria (CU) is a long-lasting and distressing condition that impairs patient quality of life (QoL) by disrupting sleep and diminishing work/school productivity. Thus treatment should not only be safe and effective but also not add to this impairment or increase risks to health or safety. Non-sedating second-generation antihistamines, with their long duration of action, pharmacodynamic properties that allow once-daily dosing and lack of drug-drug interactions and sedative effects, are the first-line symptomatic treatment option, but some patients have no adequate response to standard doses of these medications. Other therapeutic approaches to refractory urticaria have been suggested but have been limited by sparse clinical data and/or significant adverse effect profiles. Although discouraged by treatment guidelines, sedating antihistamines are frequently prescribed for nighttime use when urticaria symptoms are severe as add-on therapy to a non-sedating antihistamine. However, their pronounced effects on rapid eye movement sleep and hangover negatively impact QoL, learning and performance, and limit their use for patients in occupations that require alertness. For patients who do not respond adequately to standard doses of non-sedating second-generation antihistamines, increasing the dose of non-sedating antihistamines thus may represent the safest therapeutic approach. Given the fact that only few controlled studies have assessed the efficacy and safety of high-dose non-sedating antihistamines in CU, patient safety should be a key consideration when choosing a specific antihistamine.

  7. Benzyl alcohol protects against acetaminophen hepatotoxicity by inhibiting cytochrome P450 enzymes but causes mitochondrial dysfunction and cell death at higher doses.

    PubMed

    Du, Kuo; McGill, Mitchell R; Xie, Yuchao; Jaeschke, Hartmut

    2015-12-01

    Acetaminophen (APAP) hepatotoxicity is a serious public health problem in western countries. Current treatment options for APAP poisoning are limited and novel therapeutic intervention strategies are needed. A recent publication suggested that benzyl alcohol (BA) protects against APAP hepatotoxicity and could serve as a promising antidote for APAP poisoning. To assess the protective mechanisms of BA, C56Bl/6J mice were treated with 400 mg/kg APAP and/or 270 mg/kg BA. APAP alone caused extensive liver injury at 6 h and 24 h post-APAP. This injury was attenuated by BA co-treatment. Assessment of protein adduct formation demonstrated that BA inhibits APAP metabolic activation. In support of this, in vitro experiments also showed that BA dose-dependently inhibits cytochrome P450 activities. Correlating with the hepatoprotection of BA, APAP-induced oxidant stress and mitochondrial dysfunction were reduced. Similar results were obtained in primary mouse hepatocytes. Interestingly, BA alone caused mitochondrial membrane potential loss and cell toxicity at high doses, and its protective effect could not be reproduced in primary human hepatocytes (PHH). We conclude that BA protects against APAP hepatotoxicity mainly by inhibiting cytochrome P450 enzymes in mice. Considering its toxic effect and the loss of protection in PHH, BA is not a clinically useful treatment option for APAP overdose patient. PMID:26522885

  8. Estimation of β-ray dose in air and soil from Fukushima Daiichi Power Plant accident

    PubMed Central

    Endo, Satoru; Tanaka, Kenichi; Kajimoto, Tsuyoshi; Thanh, Nguyen Tat; Otaki, Joji M.; Imanaka, Tetsuji

    2014-01-01

    Following the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident of 2011, which deposited radionuclides across Tohoku and northern Kanto, β-ray dose evaluation has been performed to estimate radiation exposure for small creatures like insects as well as human skin. Using the Monte Carlo radiation transport code MCNP-4C, we calculated the β-ray dose for 129mTe, 129Te, 131I, 132Te, 132I, 134Cs and 137Cs in air as a function of altitude and in soil. These calculations of β-dose rate for each radionuclide were conducted for the conditions following the FDNPP accident, with 137Cs deposition assumed to be 1000 kBq/m2. Beta-ray dose rate was found to be ∼10-fold (resp. 5-fold) higher than the γ-ray dose rate in the soil (resp. on the ground surface) at ∼20 days after deposition, and ∼4-fold (resp. 1.7-fold) higher after 6 months or more. For convenience, the height dependence of the ratio for 0, 10, 30, 90, 180 and 365 days after deposition was obtained by a fitting function. The cumulative 70 µm β-ray dose at 30, 60 and 90 days after deposition was estimated to be 35, 45 and 53 mGy for the ground surface, and 61, 79 and 92 mGy in the soil, respectively. These results can be used to estimate the external β-ray exposure for small creatures as well as for human skin. PMID:24504671

  9. Low-Dose Cadmium Causes Metabolic and Genetic Dysregulation Associated With Fatty Liver Disease in Mice

    PubMed Central

    Go, Young-Mi; Sutliff, Roy L.; Chandler, Joshua D.; Khalidur, Rahman; Kang, Bum-Yong; Anania, Frank A.; Orr, Michael; Hao, Li; Fowler, Bruce A.; Jones, Dean P.

    2015-01-01

    Cadmium (Cd) is present in food at low levels and accumulates in humans throughout life because it is not effectively excreted. Cd from smoking or occupational exposure shows adverse effects on health, but the mechanistic effect of Cd at low dietary intake levels is poorly studied. Epidemiology studies found that nonalcoholic fatty liver disease (NAFLD), common in U.S. adults, is associated with Cd burden. In cell studies, we found that environmental low-dose Cd oxidized proteins and stimulated inflammatory signaling. However, little is known about low-dose Cd effects on liver function and associated metabolic pathways in vivo. We investigated effects of low-level Cd exposure on liver gene transcripts, metabolites, and associated metabolic pathways and function after challenging mice with Cd (10 mg/l) by drinking water. Results showed liver Cd in treated mice was similar to adult humans without occupational or smoking exposures and 10-fold higher than control mouse values. Pathway analysis of significantly altered liver genes and metabolites mapped to functional pathways of lipid metabolism, cell death and mitochondrial oxidative phosphorylation. These are well-recognized pathways associated with NAFLD. Cd–treated mice had higher liver enzymes in plasma and a trend toward fat accumulation in liver. To verify low-dose Cd-induced stimulation of cell death pathways, phosphorylation of c-Jun N-terminal kinase (JNK) was examined in cultured hepatic cells. Consistent with mouse liver data, low-dose Cd stimulated JNK activation. Together, the results show that low-dose Cd exposure causes liver function changes consistent with a role in NAFLD and possibly also nonalcoholic steatohepatitis. PMID:26187450

  10. Low-Dose Cadmium Causes Metabolic and Genetic Dysregulation Associated With Fatty Liver Disease in Mice.

    PubMed

    Go, Young-Mi; Sutliff, Roy L; Chandler, Joshua D; Khalidur, Rahman; Kang, Bum-Yong; Anania, Frank A; Orr, Michael; Hao, Li; Fowler, Bruce A; Jones, Dean P

    2015-10-01

    Cadmium (Cd) is present in food at low levels and accumulates in humans throughout life because it is not effectively excreted. Cd from smoking or occupational exposure shows adverse effects on health, but the mechanistic effect of Cd at low dietary intake levels is poorly studied. Epidemiology studies found that nonalcoholic fatty liver disease (NAFLD), common in U.S. adults, is associated with Cd burden. In cell studies, we found that environmental low-dose Cd oxidized proteins and stimulated inflammatory signaling. However, little is known about low-dose Cd effects on liver function and associated metabolic pathways in vivo. We investigated effects of low-level Cd exposure on liver gene transcripts, metabolites, and associated metabolic pathways and function after challenging mice with Cd (10 mg/l) by drinking water. Results showed liver Cd in treated mice was similar to adult humans without occupational or smoking exposures and 10-fold higher than control mouse values. Pathway analysis of significantly altered liver genes and metabolites mapped to functional pathways of lipid metabolism, cell death and mitochondrial oxidative phosphorylation. These are well-recognized pathways associated with NAFLD. Cd-treated mice had higher liver enzymes in plasma and a trend toward fat accumulation in liver. To verify low-dose Cd-induced stimulation of cell death pathways, phosphorylation of c-Jun N-terminal kinase (JNK) was examined in cultured hepatic cells. Consistent with mouse liver data, low-dose Cd stimulated JNK activation. Together, the results show that low-dose Cd exposure causes liver function changes consistent with a role in NAFLD and possibly also nonalcoholic steatohepatitis.

  11. H-ferritin–nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection

    PubMed Central

    Liang, Minmin; Fan, Kelong; Zhou, Meng; Duan, Demin; Zheng, Jiyan; Yang, Dongling; Feng, Jing; Yan, Xiyun

    2014-01-01

    An ideal nanocarrier for efficient drug delivery must be able to target specific cells and carry high doses of therapeutic drugs and should also exhibit optimized physicochemical properties and biocompatibility. However, it is a tremendous challenge to engineer all of the above characteristics into a single carrier particle. Here, we show that natural H-ferritin (HFn) nanocages can carry high doses of doxorubicin (Dox) for tumor-specific targeting and killing without any targeting ligand functionalization or property modulation. Dox-loaded HFn (HFn-Dox) specifically bound and subsequently internalized into tumor cells via interaction with overexpressed transferrin receptor 1 and released Dox in the lysosomes. In vivo in the mouse, HFn-Dox exhibited more than 10-fold higher intratumoral drug concentration than free Dox and significantly inhibited tumor growth after a single-dose injection. Importantly, HFn-Dox displayed an excellent safety profile that significantly reduced healthy organ drug exposure and improved the maximum tolerated dose by fourfold compared with free Dox. Moreover, because the HFn nanocarrier has well-defined morphology and does not need any ligand modification or property modulation it can be easily produced with high purity and yield, which are requirements for drugs used in clinical trials. Thus, these unique properties make the HFn nanocage an ideal vehicle for efficient anticancer drug delivery. PMID:25267615

  12. Efficacy and toxicity of decitabine versus CHG regimen (low-dose cytarabine, homoharringtonine and granulocyte colony-stimulating factor) in patients with higher risk myelodysplastic syndrome: a retrospective study.

    PubMed

    Wu, Lingyun; Li, Xiao; Chang, Chunkang; Xu, Feng; He, Qi; Wu, Dong; Zhang, Zheng; Su, Jiying; Zhou, Liyu; Song, Luxi; Chao, Xiao; Zhao, Youshan

    2016-01-01

    Decitabine and CHG regimen (low-dose cytarabine and homoharringtonine with G-CSF) have been used for treating higher risk myelodysplastic syndrome (MDS). In this study, we retrospectively compared the efficacy and toxicity of the two regimens in 132 MDS patients. Complete remission (CR) was not significantly different between the groups (27.1% with decitabine vs. 30.6% with CHG, p = 0.657). The CR rate with decitabine (58.8%) was significantly higher than that with CHG (7.7%) (p = 0.007) among the patients with poor karyotypes. Five of 23 (21.7%) patients who failed to respond to decitabine achieved CR with CHG, while one of two patients achieved CR with decitabine after failure with CHG. Overall and relapse-free survival were not different between the groups. In conclusion, both decitabine and CHG regimen are effective for higher risk MDS; there is no cross resistance between the regimens. Decitabine might be a better choice for patients with poor karyotypes.

  13. 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.

  14. Protection of Eurasian badgers (Meles meles) from tuberculosis after intra-muscular vaccination with different doses of BCG.

    PubMed

    Lesellier, Sandrine; Palmer, Si; Gowtage-Sequiera, Sonya; Ashford, Roland; Dalley, Deanna; Davé, Dipesh; Weyer, Ute; Salguero, F Javier; Nunez, Alejandro; Crawshaw, Timothy; Corner, Leigh A L; Hewinson, R Glyn; Chambers, Mark A

    2011-05-12

    Mycobacterium bovis infection is widespread in Eurasian badger (Meles meles) populations in Great Britain and the Republic of Ireland where they act as a wildlife reservoir of infection for cattle. Removal of infected badgers can significantly reduce the incidence of bovine tuberculosis (TB) in local cattle herds. However, control measures based on culling of native wildlife are contentious and may even be detrimental to disease control. Vaccinating badgers with bacillus Calmette-Guerin (BCG) has been shown to be efficacious against experimentally induced TB of badgers when administered subcutaneously and orally. Vaccination may be an alternative or complementary strategy to other disease control measures. As the subcutaneous route is impractical for vaccinating wild badgers and an oral vaccine bait formulation is currently unavailable, we evaluated the intramuscular (IM) route of BCG administration. It has been demonstrated that the IM route is safe in badgers. IM administration has the practical advantage of being relatively easy to perform on trapped wild badgers without recourse to chemical immobilisation. We report the evaluation of the efficacy of IM administration of BCG Danish strain 1331 at two different doses: the dose prescribed for adult humans (2-8×10(5)colony forming units) and a 10-fold higher dose. Vaccination generated a dose-dependent cell-mediated immune response characterised by the production of interferon-γ (IFNγ) and protection against endobronchial challenge with virulent M. bovis. Protection, expressed in terms of a significant reduction in the severity of disease, the number of tissues containing acid-fast bacilli, and reduced bacterial excretion was statistically significant with the higher dose only.

  15. Nicotine dose-concentration relationship and pregnancy outcomes in rat: Biologic plausibility and implications for future research

    SciTech Connect

    Hussein, Jabeen; Farkas, Svetlana; MacKinnon, Yolanda; Ariano, Robert E.; Sitar, Daniel S.; Hasan, Shabih U. . E-mail: hasans@ucalgary.ca

    2007-01-01

    Cigarette smoke (CS) exposure during pregnancy can lead to profound adverse effects on fetal development. Although CS contains several thousand chemicals, nicotine has been widely used as its surrogate as well as in its own right as a neuroteratogen. The justification for the route and dose of nicotine administration is largely based on inferential data suggesting that nicotine 6 mg/kg/day infused continuously via osmotic mini pumps (OMP) would mimic maternal CS exposure. We provide evidence that 6 mg/kg/day nicotine dose as commonly administered to pregnant rats leads to plasma nicotine concentrations that are 3-10-fold higher than those observed in moderate to heavy smokers and pregnant mothers, respectively. Furthermore, the cumulative daily nicotine dose exceeds by several hundred fold the amount consumed by human heavy smokers. Our study does not support the widely accepted notion that regardless of the nicotine dose, a linear nicotine dose-concentration relationship exists in a steady-state OMP model. We also show that total nicotine clearance increases with advancing pregnancy but no significant change is observed between the 2nd and 3rd trimester. Furthermore, nicotine infusion even at this extremely high dose has little effect on a number of maternal and fetal biologic variables and pregnancy outcome suggesting that CS constituents other than nicotine mediate the fetal growth restriction in infants born to smoking mothers. Our current study has major implications for translational research in developmental toxicology and pharmacotherapy using nicotine replacement treatment as an aid to cessation of cigarette smoking in pregnant mothers.

  16. Know your dose: RADDOSE

    PubMed Central

    Paithankar, Karthik S.; Garman, Elspeth F.

    2010-01-01

    The program RADDOSE is widely used to compute the dose absorbed by a macromolecular crystal during an X-ray diffraction experiment. A number of factors affect the absorbed dose, including the incident X-ray flux density, the photon energy and the composition of the macromolecule and of the buffer in the crystal. An experimental dose limit for macromolecular crystallography (MX) of 30 MGy at 100 K has been reported, beyond which the biological information obtained may be compromised. Thus, for the planning of an optimized diffraction experiment the estimation of dose has become an additional tool. A number of approximations were made in the original version of RADDOSE. Recently, the code has been modified in order to take into account fluorescent X-­ray escape from the crystal (version 2) and the inclusion of incoherent (Compton) scattering into the dose calculation is now reported (version 3). The Compton cross-section, although negligible at the energies currently commonly used in MX, should be considered in dose calculations for incident energies above 20 keV. Calculations using version 3 of RADDOSE reinforce previous studies that predict a reduction in the absorbed dose when data are collected at higher energies compared with data collected at 12.4 keV. Hence, a longer irradiation lifetime for the sample can be achieved at these higher energies but this is at the cost of lower diffraction intensities. The parameter ‘diffraction-dose efficiency’, which is the diffracted intensity per absorbed dose, is revisited in an attempt to investigate the benefits and pitfalls of data collection using higher and lower energy radiation, particularly for thin crystals. PMID:20382991

  17. Circulating endothelial progenitor cells and residual in vivo thromboxane biosynthesis in low-dose aspirin-treated polycythemia vera patients.

    PubMed

    Santilli, Francesca; Romano, Mario; Recchiuti, Antonio; Dragani, Alfredo; Falco, Angela; Lessiani, Gianfranco; Fioritoni, Francesca; Lattanzio, Stefano; Mattoscio, Domenico; De Cristofaro, Raimondo; Rocca, Bianca; Davì, Giovanni

    2008-08-15

    Polycythemia vera (PV) is associated with high morbidity and mortality for thrombosis. We hypothesized that in PV altered sensitivity to aspirin might be related to dysfunction of the endothelial repair and/or of the nitric oxide (NO) system. Urinary thromboxane (TX) A(2) metabolite (TXM), endothelial colony-forming cells (ECFCs), plasma asymmetric dimethylarginine (ADMA) and von Willebrand factor (VWF) were measured in 37 PV patients on low-dose aspirin and 12 healthy controls. Patients showed an approximately 2-fold increase in median TXM and plasma ADMA levels (P < .001), while ECFC numbers were reduced by approximately 7-fold (P < .001) as compared with non-aspirinated control. These differences were more pronounced in patients with previous thrombosis. An 8-week course of aspirin did not affect ECFCs in 6 controls. VWF and TXM correlated directly with ADMA, and inversely with ECFCs. By multiple regression analysis, lower ECFC quartiles (beta = -0.39; SE = 0.17; P = .028) and higher VWF levels (beta = 0.338, SE = 0.002, P = .034) were independent predictors of higher TXM quartiles (R(2) = 0.39). Serum TXB(2), measured in 22 patients, was approximately 10-fold higher than aspirin-treated controls. PV patients appear to have an unbalanced ECFC/NO axis, and an apparent altered sensitivity of platelet TXA(2) production, all potentially contributing to aspirin-insensitive TXM formation. Thus, additional antithrombotic strategies may be beneficial in PV. PMID:18541722

  18. A combination of high dose rate (10X FFF/2400 MU/min/10 MV X-rays) and total low dose (0.5 Gy) induces a higher rate of apoptosis in melanoma cells in vitro and superior preservation of normal melanocytes.

    PubMed

    Sarojini, Sreeja; Pecora, Andrew; Milinovikj, Natasha; Barbiere, Joseph; Gupta, Saakshi; Hussain, Zeenathual M; Tuna, Mehmet; Jiang, Jennifer; Adrianzen, Laura; Jun, Jaewook; Catello, Laurice; Sanchez, Diana; Agarwal, Neha; Jeong, Stephanie; Jin, Youngjin; Remache, Yvonne; Goy, Andre; Ndlovu, Alois; Ingenito, Anthony; Suh, K Stephen

    2015-10-01

    The aim of this study was to determine the apoptotic effects, toxicity, and radiosensitization of total low dose irradiation delivered at a high dose rate in vitro to melanoma cells, normal human epidermal melanocytes (HEM), or normal human dermal fibroblasts (HDF) and to study the effect of mitochondrial inhibition in combination with radiation to enhance apoptosis in melanoma cells. Cells irradiated using 10X flattening filter-free (FFF) 10 MV X-rays at a dose rate of 400 or 2400 MU/min and a total dose of 0.25-8 Gy were analyzed by cell/colony counting, MitoTracker, MTT, and DNA-damage assays, as well as by quantitative real-time reverse transcriptase PCR in the presence or absence of mitochondrial respiration inhibitors. A dose rate of 2400 MU/min killed on average five-fold more melanoma cells than a dose rate 400 MU/min at a total dose of 0.5 Gy and preserved 80% survival of HEM and 90% survival of HDF. Increased apoptosis at the 2400 MU/min dose rate is mediated by greater DNA damage, reduced cell proliferation, upregulation of apoptotic genes, and downregulation of cell cycle genes. HEM and HDF were relatively unharmed at 2400 MU/min. Radiation induced upregulation of mitochondrial respiration in both normal and cancer cells, and blocking the respiration with inhibitors enhanced apoptosis only in melanoma cells. A high dose rate with a low total dose (2400 MU/min, 0.5 Gy/10X FFF 10 MV X-rays) enhances radiosensitivity of melanoma cells while reducing radiotoxicity toward HEM and HDF. Selective cytotoxicity of melanoma cells is increased by blocking mitochondrial respiration.

  19. A combination of high dose rate (10X FFF/2400 MU/min/10 MV X-rays) and total low dose (0.5 Gy) induces a higher rate of apoptosis in melanoma cells in vitro and superior preservation of normal melanocytes

    PubMed Central

    Sarojini, Sreeja; Pecora, Andrew; Milinovikj, Natasha; Barbiere, Joseph; Gupta, Saakshi; Hussain, Zeenathual M.; Tuna, Mehmet; Jiang, Jennifer; Adrianzen, Laura; Jun, Jaewook; Catello, Laurice; Sanchez, Diana; Agarwal, Neha; Jeong, Stephanie; Jin, Youngjin; Remache, Yvonne; Goy, Andre; Ndlovu, Alois; Ingenito, Anthony

    2015-01-01

    The aim of this study was to determine the apoptotic effects, toxicity, and radiosensitization of total low dose irradiation delivered at a high dose rate in vitro to melanoma cells, normal human epidermal melanocytes (HEM), or normal human dermal fibroblasts (HDF) and to study the effect of mitochondrial inhibition in combination with radiation to enhance apoptosis in melanoma cells. Cells irradiated using 10X flattening filter-free (FFF) 10 MV X-rays at a dose rate of 400 or 2400 MU/min and a total dose of 0.25–8 Gy were analyzed by cell/colony counting, MitoTracker, MTT, and DNA-damage assays, as well as by quantitative real-time reverse transcriptase PCR in the presence or absence of mitochondrial respiration inhibitors. A dose rate of 2400 MU/min killed on average five-fold more melanoma cells than a dose rate 400 MU/min at a total dose of 0.5 Gy and preserved 80% survival of HEM and 90% survival of HDF. Increased apoptosis at the 2400 MU/min dose rate is mediated by greater DNA damage, reduced cell proliferation, upregulation of apoptotic genes, and downregulation of cell cycle genes. HEM and HDF were relatively unharmed at 2400 MU/min. Radiation induced upregulation of mitochondrial respiration in both normal and cancer cells, and blocking the respiration with inhibitors enhanced apoptosis only in melanoma cells. A high dose rate with a low total dose (2400 MU/min, 0.5 Gy/10X FFF 10 MV X-rays) enhances radiosensitivity of melanoma cells while reducing radiotoxicity toward HEM and HDF. Selective cytotoxicity of melanoma cells is increased by blocking mitochondrial respiration. PMID:26177150

  20. Evolution of zinc, iron, and copper concentrations along the gastrointestinal tract of piglets weaned with or without in-feed high doses of zinc oxide compared to unweaned littermates.

    PubMed

    Davin, R; Manzanilla, E G; Klasing, K C; Pérez, J F

    2012-12-01

    High doses of ZnO are used to treat diarrhea in weaning pigs but are also an environmental concern. The mechanism of action of Zn against diarrhea is still not well understood. The amount of solubilized Zn, the relation of Zn with Fe and Cu, and the concentration of these elements in the gastrointestinal tract (GIT) are key data to understanding its mechanism of action and optimize its use. Therefore, we studied the Zn, Fe, and Cu concentrations in the GIT content of unweaned, weaned, and ZnO-treated pigs. Eight litters were used and 3 piglets were selected within each litter. Two piglets from each litter were weaned at 21 d of age and fed a commercial control diet (WCt) or WCt + 2000 mg/kg of Zn as ZnO (WZn). The third pig was kept unweaned (Uw) with the sow. All 24 pigs were killed at 28 d of age, GIT contents were sampled, soluble and insoluble fractions of the content were separated, and Zn, Fe, and Cu concentrations were analyzed. Concentration of Zn increased 3 to 5 fold along the GIT (2 to 10 fold in the soluble fraction) for weaned pigs on WZn compared to WCt and Uw pigs (P < 0.01 in all cases). The proportion of total Zn that was present in the soluble fraction was 4 to 10 folds higher in jejunum, ileum, and cecum of Uw pigs than in those weaned (P < 0.01 in all cases) but was not affected by ZnO treatment. Concentration of Fe in the soluble fraction was higher for Uw pigs compared to weaned pigs along the GIT (P < 0.05 in all cases) even when concentration in total content was lower for Uw pigs in stomach (P = 0.001) and jejunum (P = 0.029). Concentrations of Cu were lower in Uw pigs than in weaned pigs along the GIT (P < 0.05 in all cases). Surprisingly, animals on WZn showed a 5 to 10 fold increase of Cu solubilized in distal parts of the GIT (cecum and colon; P < 0.001) compared to other groups. Differences in Zn, Fe, and Cu concentrations found among treatments will be useful in future studies for understanding mechanism of action of ZnO and

  1. Evolution of zinc, iron, and copper concentrations along the gastrointestinal tract of piglets weaned with or without in-feed high doses of zinc oxide compared to unweaned littermates.

    PubMed

    Davin, R; Manzanilla, E G; Klasing, K C; Pérez, J F

    2012-12-01

    High doses of ZnO are used to treat diarrhea in weaning pigs but are also an environmental concern. The mechanism of action of Zn against diarrhea is still not well understood. The amount of solubilized Zn, the relation of Zn with Fe and Cu, and the concentration of these elements in the gastrointestinal tract (GIT) are key data to understanding its mechanism of action and optimize its use. Therefore, we studied the Zn, Fe, and Cu concentrations in the GIT content of unweaned, weaned, and ZnO-treated pigs. Eight litters were used and 3 piglets were selected within each litter. Two piglets from each litter were weaned at 21 d of age and fed a commercial control diet (WCt) or WCt + 2000 mg/kg of Zn as ZnO (WZn). The third pig was kept unweaned (Uw) with the sow. All 24 pigs were killed at 28 d of age, GIT contents were sampled, soluble and insoluble fractions of the content were separated, and Zn, Fe, and Cu concentrations were analyzed. Concentration of Zn increased 3 to 5 fold along the GIT (2 to 10 fold in the soluble fraction) for weaned pigs on WZn compared to WCt and Uw pigs (P < 0.01 in all cases). The proportion of total Zn that was present in the soluble fraction was 4 to 10 folds higher in jejunum, ileum, and cecum of Uw pigs than in those weaned (P < 0.01 in all cases) but was not affected by ZnO treatment. Concentration of Fe in the soluble fraction was higher for Uw pigs compared to weaned pigs along the GIT (P < 0.05 in all cases) even when concentration in total content was lower for Uw pigs in stomach (P = 0.001) and jejunum (P = 0.029). Concentrations of Cu were lower in Uw pigs than in weaned pigs along the GIT (P < 0.05 in all cases). Surprisingly, animals on WZn showed a 5 to 10 fold increase of Cu solubilized in distal parts of the GIT (cecum and colon; P < 0.001) compared to other groups. Differences in Zn, Fe, and Cu concentrations found among treatments will be useful in future studies for understanding mechanism of action of ZnO and

  2. Dose Titration of Walleye Dermal Sarcoma (WDS) Tumor Filtrate.

    PubMed

    Getchell, R G; Wooster, G A; Sutton, C A; Casey, J W; Bowser, P R

    2006-12-01

    Walleyes Stizostedion vitreum were challenged with a topical application of a dilution series of cell-free dermal sarcoma tumor filtrates to determine the minimum dose of virus needed to induce these walleye tumors. A series of six 10-fold dilutions of the filtrate were applied to the side of the fish, which were allowed to develop grossly visible tumors at 15°C for 20 weeks. Quantification of the virus in the filtrates was accomplished by quantitative (real-time) reverse transcriptase-polymerase chain reaction. We determined that there are approximately 10(10) viral RNA copies in 100 μL of walleye dermal sarcoma inoculum. The minimum dose of walleye dermal sarcoma virus that could induce tumors by the topical challenge method was the 1,000-fold dilution of this 10(10) inoculum, or approximately 10(7) viral RNA copies.

  3. [High dose rate brachytherapy].

    PubMed

    Aisen, S; Carvalho, H A; Chavantes, M C; Esteves, S C; Haddad, C M; Permonian, A C; Taier, M do C; Marinheiro, R C; Feriancic, C V

    1992-01-01

    The high dose rate brachytherapy uses a single source os 192Ir with 10Ci of nominal activity in a remote afterloading machine. This technique allows an outpatient treatment, without the inconveniences of the conventional low dose rate brachytherapy such as use of general anesthesia, rhachianesthesia, prolonged immobilization, and personal exposition to radiation. The radiotherapy department is now studying 5 basic treatment schemes concerning carcinomas of the uterine cervix, endometrium, lung, esophagus and central nervous system tumors. With the Micro Selectron HDR, 257 treatment sessions were done in 90 patients. Mostly were treated with weekly fractions, receiving a total of three to four treatments each. No complications were observed neither during nor after the procedure. Doses, fraction and ideal associations still have to be studied, so that a higher therapeutic ratio can be reached.

  4. Higher Education or Higher Skilling?

    ERIC Educational Resources Information Center

    Muller, Steven

    1974-01-01

    Higher education may return to education for a minority, an unlikely course; concentrate on higher skilling, the road we are on today; or restore general education, the most attractive possibility, which can be implemented by restoring basic education in literacy, history, human biology, and language. (JH)

  5. Higher Education.

    ERIC Educational Resources Information Center

    Hendrickson, Robert M.

    This eighth chapter of "The Yearbook of School Law, 1986" summarizes and analyzes over 330 state and federal court cases litigated in 1985 in which institutions of higher education were involved. Among the topics examined were relationships between postsecondary institutions and various governmental agencies; discrimination in the employment of…

  6. Higher Education.

    ERIC Educational Resources Information Center

    Hendrickson, Robert M.; Gregory, Dennis E.

    Decisions made by federal and state courts during 1983 concerning higher education are reported in this chapter. Issues of employment and the treatment of students underlay the bulk of the litigation. Specific topics addressed in these and other cases included federal authority to enforce regulations against age discrimination and to revoke an…

  7. Higher Education.

    ERIC Educational Resources Information Center

    Hendrickson, Robert M.

    Litigation in 1987 was very brisk with an increase in the number of higher education cases reviewed. Cases discussed in this chapter are organized under four major topics: (1) intergovernmental relations; (2) employees, involving discrimination claims, tenured and nontenured faculty, collective bargaining and denial of employee benefits; (3)…

  8. Higher Education.

    ERIC Educational Resources Information Center

    Hendrickson, Robert M.; Finnegan, Dorothy E.

    The higher education case law in 1988 is extensive. Cases discussed in this chapter are organized under five major topics: (1) intergovernmental relations; (2) employees, involving discrimination claims, tenured and nontenured faculty, collective bargaining, and denial of employee benefits; (3) students, involving admissions, financial aid, First…

  9. Higher Learning.

    ERIC Educational Resources Information Center

    Bok, Derek

    Factors that distinguish the United States higher education system and its performance are considered, with attention to new developments, propsects for change, undergraduate education, and professional schools (especially law, business, and medicine). The way universities change the methods and content of their teaching in response to new…

  10. Artemether-lumefantrine nanostructured lipid carriers for oral malaria therapy: Enhanced efficacy at reduced dose and dosing frequency.

    PubMed

    Prabhu, Priyanka; Suryavanshi, Shital; Pathak, Sulabha; Sharma, Shobhona; Patravale, Vandana

    2016-09-10

    Artemether-lumefantrine (ARM-LFN) is a World Health Organization (WHO) approved fixed-dose combination having low solubility and poor oral bioavailability. Nanostructured lipid carriers (NLC) were developed to enhance the oral efficacy of this combination using the microemulsion template technique. They were characterized for drug content, entrapment efficiency, size distribution, in vitro release, antimalarial efficacy, and toxicity. The NLC showed sustained drug release. The recommended adult therapeutic dose is 80mg ARM and 480mg LFN (4 tablets) twice a day, which amounts to 160mg ARM and 960mg LFN daily. ARM-LFN NLC given once a day at 1/5 of therapeutic dose (16mg ARM and 96mg LFN) showed complete parasite clearance and 100% survival in Plasmodium berghei-infected mice. 33% of the mice treated with marketed tablets twice a day at the therapeutic dose showed late-stage recrudescence. Thus, NLC showed enhanced efficacy at 1/10 of the daily dose of ARM-LFN. The 10-fold reduced daily dose was formulated in two soft gelatin capsules thus reducing the number of units to be taken at a time by the patient. The capsules showed good stability at room temperature for a year. The NLC were found to be safe in rats. The biocompatible NLC developed using an industrially feasible technique offer a promising solution for oral malaria therapy. PMID:27421912

  11. Advantages of Efficacy and Safety of Fixed-Dose Tafluprost/Timolol Combination Over Fixed-Dose Latanoprost/Timolol Combination

    PubMed Central

    Fuwa, Masahiro; Ueda, Kenji; Akaishi, Takahiro; Yamashita, Naoko; Kirihara, Tomoko; Shimazaki, Atsushi; Mano, Hidetoshi; Kawazu, Kouichi

    2016-01-01

    Purpose To compare the safety and efficacy of fixed-dose tafluprost/timolol combination (Taf/T-FDC) with those of fixed-dose latanoprost/timolol combination (Lat/T-FDC) by measuring the intraocular pressure (IOP)-lowering effect, ocular pharmacokinetics, and ocular surface toxicity. Methods The IOP-lowering effect of Taf/T-FDC and Lat/T-FDC in ocular normotensive monkeys was evaluated at 4 and 8 h after instillation in study A, at 12, 14, 16, and 18 h after instillation in study B, and at 24, 26, 28, and 30 h after instillation in study C. Drug penetration into the eye was evaluated by measuring the concentrations of timolol, tafluprost acid (active metabolic form of tafluprost), and latanoprost acid (active metabolic form of latanoprost) using liquid chromatography coupled with tandem mass spectrometry after single instillation of Taf/T-FDC or Lat/T-FDC to Sprague Dawley rats. Cytotoxicity following 1–30 min exposure of SV40-transformed human corneal epithelial cells to Taf/T-FDC or Lat/T-FDC was analyzed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assays. Undiluted and 10-fold diluted solutions of each FDC were evaluated. Results The IOP-lowering effect of Taf/T-FDC was almost equivalent to that of Lat/T-FDC at 4–8 h after instillation. The peak IOP reduction of Taf/T-FDC and Lat/T-FDC was observed at 8 h after instillation, and there is no difference between the two. The difference between them was observed at 24–30 h after instillation, and Taf/T-FDC demonstrated a significantly greater IOP-lowering effect than Lat/T-FDC at 24–30 h after instillation. The IOP-lowering effect of Taf/T-FDC was sustained up to 30 h after instillation, while that of Lat/T-FDC had almost disappeared at 28 h after instillation. Timolol concentrations in aqueous humor after Taf/T-FDC instillation were higher than those after Lat/T-FDC instillation (Cmax, 3870 ng/mL vs 1330 ng/mL; AUCinf, 3970 ng·h/mL vs 1250 ng·h/mL). The

  12. Gamma Radiation Doses In Sweden

    SciTech Connect

    Almgren, Sara; Isaksson, Mats; Barregaard, Lars

    2008-08-07

    Gamma dose rate measurements were performed in one urban and one rural area using thermoluminescence dosimeters (TLD) worn by 46 participants and placed in their dwellings. The personal effective dose rates were 0.096{+-}0.019(1 SD) and 0.092{+-}0.016(1 SD){mu}Sv/h in the urban and rural area, respectively. The corresponding dose rates in the dwellings were 0.11{+-}0.042(1 SD) and 0.091{+-}0.026(1 SD){mu}Sv/h. However, the differences between the areas were not significant. The values were higher in buildings made of concrete than of wood and higher in apartments than in detached houses. Also, {sup 222}Rn measurements were performed in each dwelling, which showed no correlation with the gamma dose rates in the dwellings.

  13. Mean dose to lymphocytes during radiotherapy treatments

    SciTech Connect

    Brandan, M.E.; Perez-Pastenes, M.A.; Ostrosky-Wegman, P.; Gonsebatt, M.E.; Diaz-Perches, R.

    1994-10-01

    Using a probabilistic model with parameters from four radiotherapy protocols used in Mexican hospitals for the treatment of cervical cancer, the authors have calculated the distribution of dose to cells in peripheral blood of patients. Values of the mean dose to the lymphocytes during and after a {sup 60}Co treatment are compared to estimates from an in vivo chromosome aberration study performed on five patients. Calculations indicate that the mean dose to the circulating blood is about 2% of the tumor dose, while the mean dose to recirculating lymphocytes may reach up to 7% of the tumor dose. Differences up to a factor of two in the dose to the blood are predicted for different protocols delivering equal tumor doses. The data suggest mean doses higher than the predictions of the model. 10 refs., 3 figs., 2 tabs.

  14. Advax delta inulin adjuvant overcomes immune immaturity in neonatal mice thereby allowing single-dose influenza vaccine protection.

    PubMed

    Honda-Okubo, Yoshikazu; Ong, Chun Hao; Petrovsky, Nikolai

    2015-09-11

    Neonates are at high risk for influenza morbidity and mortality due to immune immaturity and lack of priming by prior influenza virus exposure. Inactivated influenza vaccines are ineffective in infants under six months and to provide protection in older children generally require two doses given a month apart. This leaves few options for rapid protection of infants, e.g. during an influenza pandemic. We investigated whether Advax™, a novel polysaccharide adjuvant based on delta inulin microparticles could help overcome neonatal immune hypo-responsiveness. We first tested whether it was possible to use Advax to obtain single-dose vaccine protection of neonatal pups against lethal influenza infection. Inactivated influenza A/H1N1 vaccine (iH1N1) combined with Advax™ adjuvant administered as a single subcutaneous immunization to 7-day-old mouse pups significantly enhanced serum influenza-specific IgM, IgG1, IgG2a and IgG2b levels and was associated with a 3-4 fold increase in the frequency of splenic influenza-specific IgM and IgG antibody secreting cells. Pups immunized with Advax had significantly higher splenocyte influenza-stimulated IFN-γ, IL-2, IL-4, and IL-10 production by CBA and a 3-10 fold higher frequency of IFN-γ, IL-2, IL-4 or IL-17 secreting T cells by ELISPOT. Immunization with iH1N1+Advax induced robust protection of pups against virus challenge 3 weeks later, whereas pups immunized with iH1N1 antigen alone had no protection. Protection by Advax-adjuvanted iH1N1 was dependent on memory B cells rather than memory T cells, with no protection in neonatal μMT mice that are B-cell deficient. Hence, Advax adjuvant overcame neonatal immune hypo-responsiveness and enabled single-dose protection of pups against otherwise lethal influenza infection, thereby supporting ongoing development of Advax™ as a neonatal vaccine adjuvant.

  15. Advax Delta Inulin Adjuvant Overcomes Immune Immaturity In Neonatal Mice Thereby Allowing Single–Dose Influenza Vaccine Protection

    PubMed Central

    Honda-Okubo, Yoshikazu; Ong, Chun Hao; Petrovsky, Nikolai

    2015-01-01

    Neonates are at high risk for influenza morbidity and mortality due to immune immaturity and lack of priming by prior exposure. Inactivated influenza vaccines are ineffective in infants under six months and to provide protection in older children generally require two doses given a month apart. This leaves few options for rapid protection of infants, e.g. during an influenza pandemic. We investigated whether Advax™, a novel polysaccharide adjuvant based on delta inulin microparticles could help overcome neonatal immune hypo-responsiveness and also whether it was possible to obtain single-dose influenza vaccine protection of babies against lethal infection. Inactivated influenza A/H1N1 vaccine (iH1N1) combined with Advax™ adjuvant administered as a single immunization to 7-day-old mouse pups significantly enhanced serum influenza-specific IgM, IgG1, IgG2a and IgG2b levels in association with a 3–4 fold increase in the frequency of splenic influenza-specific IgM and IgG antibody secreting cells versus pups immunized with iH1N1 alone. Pups immunized with Advax-adjuvanted iH1N1 had significantly higher influenza-stimulated splenocyte production of IFN-γ, IL-2, IL-4, and IL-10 and a 3–10 fold higher frequency of T cells IFN-γ secreting IL-2, IL-4 or IL-17 by ELISPOT. Immunisation with iH1N1+Advax adjuvant induced robust protection against influenza virus challenge 3 weeks post-immunization, whereas pups immunized with iH1N1 alone had no protection. Protection by Advax-adjuvanted iH1N1 was mediated by serum antibody and memory B cells rather than memory T cells as protection was lost in neonatal µMT mice that are B-cell deficient. Hence, Advax adjuvant overcame neonatal immune hypo-responsiveness and enabled single-dose protection of pups against otherwise lethal influenza infection, thereby supporting development of Advax™ as a neonatal vaccine adjuvant. PMID:26232344

  16. 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

  17. Benchmark Dose Modeling

    EPA Science Inventory

    Finite doses are employed in experimental toxicology studies. Under the traditional methodology, the point of departure (POD) value for low dose extrapolation is identified as one of these doses. Dose spacing necessarily precludes a more accurate description of the POD value. ...

  18. Dose dependent pharmacokinetics of naproxen in man.

    PubMed

    Niazi, S K; Alam, S M; Ahmad, S I

    1996-05-01

    The pharmacokinetics of one of the most widely used non-steroidal antiinflammatory drugs, naproxen, were studied in 28 healthy human volunteers at the two most commonly used dose levels, viz., 250 mg and 500 mg, in a cross-over design. The plasma levels of naproxen were analysed by a modified high-pressure liquid chromatography method. The plasma concentrations at higher doses were not proportional to dose, indicating a non-linearity in the pharmacokinetics at the dose levels studied; this finding is new since earlier studies had studied only higher doses and assumed that at lower doses the pharmacokinetics would be linear. There was, however, no significant difference in the elimination half-life (rate constant), time to reach peak concentration (Cmax), mean residence time (MRT), or area under first moment curve (AUMC). The clearance and distribution volume of naproxen were substantially increased at higher dose resulting in statistically lower proportional concentration and the total area under the curve (AUC). These observations are explained on the basis of a change in the plasma protein binding resulting in more free naproxen available for quicker clearance and wider penetration into tissues. These findings have several important clinical implications for the long-term use of naproxen as an antiarthritic drug. It is proposed that the clinical efficacy of naproxen can be increased and side-effects reduced by giving it in small divided doses instead of large doses.

  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. From cellular doses to average lung dose.

    PubMed

    Hofmann, W; Winkler-Heil, R

    2015-11-01

    Sensitive basal and secretory cells receive a wide range of doses in human bronchial and bronchiolar airways. Variations of cellular doses arise from the location of target cells in the bronchial epithelium of a given airway and the asymmetry and variability of airway dimensions of the lung among airways in a given airway generation and among bronchial and bronchiolar airway generations. To derive a single value for the average lung dose which can be related to epidemiologically observed lung cancer risk, appropriate weighting scenarios have to be applied. Potential biological weighting parameters are the relative frequency of target cells, the number of progenitor cells, the contribution of dose enhancement at airway bifurcations, the promotional effect of cigarette smoking and, finally, the application of appropriate regional apportionment factors. Depending on the choice of weighting parameters, detriment-weighted average lung doses can vary by a factor of up to 4 for given radon progeny exposure conditions.

  1. Reevaluation of the newborn thyroid dose from radioiodines

    SciTech Connect

    Hedrick, W.R.; Milavickas, L.R.

    1987-07-01

    The basis for the current thyroid absorbed dose estimates for radioiodines has been examined. The values for the newborn thyroid dose were found to underestimate the dose by a factor of 3. This underestimation of the dose was caused by the assumption that the biokinetic distribution of iodine is the same for the newborn and the adult. Increased thyroid uptake by the newborn requires that higher cumulated activities be incorporated into the dose determinations for the newborn.

  2. Validation of Early Human Dose Prediction: A Key Metric for Compound Progression in Drug Discovery.

    PubMed

    Page, Ken M

    2016-02-01

    Human dose prediction is increasingly recognized as an important parameter in Drug Discovery. Validation of a method using only in vitro and predicted parameters incorporated into a PK model was undertaken by predicting human dose and free Cmax for a number of marketed drugs and AZ Development compounds. Doses were compared to those most relevant to marketed drugs or to clinically administered doses of AZ compounds normalized either to predicted Cmin or Cmax values. Average (AFE) and absolute average (AAFE) fold-error analysis showed that best predictions were obtained using a QSAR model as the source of Vss, with Fabs set to 1 for acids and 0.5 for all other ion classes; for clearance prediction no binding correction to the well stirred model (WSM) was used for bases, while it was set to Fup/Fup(0.5) for all other ion classes. Using this combination of methods, predicted doses for 45 to 68% of the Cmin- and Cmax-normalized and marketed drug data sets were within 3-fold of the observed values, while 82 to 92% of these data sets were within 10-fold. This method for early human dose prediction is able to rank, identify, and flag risks or optimization opportunities for future development compounds within 10 days of first synthesis. PMID:26696327

  3. Use of effective dose.

    PubMed

    Harrison, J D; Balonov, M; Martin, C J; Ortiz Lopez, P; Menzel, H-G; Simmonds, J R; Smith-Bindman, R; Wakeford, R

    2016-06-01

    International Commission on Radiological Protection (ICRP) Publication 103 provided a detailed explanation of the purpose and use of effective dose and equivalent dose to individual organs and tissues. Effective dose has proven to be a valuable and robust quantity for use in the implementation of protection principles. However, questions have arisen regarding practical applications, and a Task Group has been set up to consider issues of concern. This paper focusses on two key proposals developed by the Task Group that are under consideration by ICRP: (1) confusion will be avoided if equivalent dose is no longer used as a protection quantity, but regarded as an intermediate step in the calculation of effective dose. It would be more appropriate for limits for the avoidance of deterministic effects to the hands and feet, lens of the eye, and skin, to be set in terms of the quantity, absorbed dose (Gy) rather than equivalent dose (Sv). (2) Effective dose is in widespread use in medical practice as a measure of risk, thereby going beyond its intended purpose. While doses incurred at low levels of exposure may be measured or assessed with reasonable reliability, health effects have not been demonstrated reliably at such levels but are inferred. However, bearing in mind the uncertainties associated with risk projection to low doses or low dose rates, it may be considered reasonable to use effective dose as a rough indicator of possible risk, with the additional consideration of variation in risk with age, sex and population group. PMID:26980800

  4. Use of effective dose.

    PubMed

    Harrison, J D; Balonov, M; Martin, C J; Ortiz Lopez, P; Menzel, H-G; Simmonds, J R; Smith-Bindman, R; Wakeford, R

    2016-06-01

    International Commission on Radiological Protection (ICRP) Publication 103 provided a detailed explanation of the purpose and use of effective dose and equivalent dose to individual organs and tissues. Effective dose has proven to be a valuable and robust quantity for use in the implementation of protection principles. However, questions have arisen regarding practical applications, and a Task Group has been set up to consider issues of concern. This paper focusses on two key proposals developed by the Task Group that are under consideration by ICRP: (1) confusion will be avoided if equivalent dose is no longer used as a protection quantity, but regarded as an intermediate step in the calculation of effective dose. It would be more appropriate for limits for the avoidance of deterministic effects to the hands and feet, lens of the eye, and skin, to be set in terms of the quantity, absorbed dose (Gy) rather than equivalent dose (Sv). (2) Effective dose is in widespread use in medical practice as a measure of risk, thereby going beyond its intended purpose. While doses incurred at low levels of exposure may be measured or assessed with reasonable reliability, health effects have not been demonstrated reliably at such levels but are inferred. However, bearing in mind the uncertainties associated with risk projection to low doses or low dose rates, it may be considered reasonable to use effective dose as a rough indicator of possible risk, with the additional consideration of variation in risk with age, sex and population group.

  5. Ideal dose level in treatment planning optimization.

    PubMed

    Begnozzi, L; Malaspina, F; Gentile, F P; Chiatti, L; Carpino, S; Fragomeni, R; Benassi, M

    1992-10-01

    The biological response of the tumor is expressed in terms of tumor control probability (TCP) and its dependence on the inhomogeneous dose distribution throughout the tumor volume is studied. The ideal dose level to which the prescribed dose must be referred is derived, by employing a formula based on the linear quadratic model. To administer the prescribed dose to the ideal dose level renders the tumor control probability equal to that one corresponding to a uniform irradiation of the tumor. For the normal tissue irradiated a normal tissue complication probability index (NTCPI) is also defined and calculated. The comparison between NTCPIs of competing plans supports the optimization. In general the resulting ideal dose level is lower than the mean dose level, but not necessarily equal to the minimum in the tumor. This result shows the possibility of administering the prescribed dose to a dose level higher than the minimum, maintaining the tumor control probability at a good level and consequently lowering the complications to the normal tissue. The method offers a general support for the choice of the reference dose level and of the better technique. An example of application of the method is shown.

  6. Absorbed dose thresholds and absorbed dose rate limitations for studies of electron radiation effects on polyetherimides

    NASA Technical Reports Server (NTRS)

    Long, Edward R., Jr.; Long, Sheila Ann T.; Gray, Stephanie L.; Collins, William D.

    1989-01-01

    The threshold values of total absorbed dose for causing changes in tensile properties of a polyetherimide film and the limitations of the absorbed dose rate for accelerated-exposure evaluation of the effects of electron radiation in geosynchronous orbit were studied. Total absorbed doses from 1 kGy to 100 MGy and absorbed dose rates from 0.01 MGy/hr to 100 MGy/hr were investigated, where 1 Gy equals 100 rads. Total doses less than 2.5 MGy did not significantly change the tensile properties of the film whereas doses higher than 2.5 MGy significantly reduced elongation-to-failure. There was no measurable effect of the dose rate on the tensile properties for accelerated electron exposures.

  7. High-Dose Atomoxetine Treatment of ADHD in Youths with Limited Response to Standard Doses

    ERIC Educational Resources Information Center

    Kratochvil, Christopher J.; Michelson, David; Newcorn, Jeffrey H.; Weiss, Margaret D.; Busner, Joan; Moore, Rodney J.; Ruff, Dustin D.; Ramsey, Janet; Dickson, Ruth; Turgay, Atilla; Saylor, Keith E.; Luber, Stephen; Vaughan, Brigette; Allen, Albert J.

    2007-01-01

    Objective: To assess the utility and tolerability of higher than standard atomoxetine doses to treat attention-deficit/hyperactivity disorder (ADHD). Method: Two randomized, double-blind trials of atomoxetine nonresponders ages 6 to 16 years were conducted comparing continued treatment with same-dose atomoxetine to treatment using greater than…

  8. Perchlorate exposure and dose estimates in infants

    PubMed Central

    Valentín-Blasini, Liza; Blount, Benjamin C.; Otero-Santos, Samaret; Cao, Yang; Bernbaum, Judy C.; Rogan, Walter J.

    2011-01-01

    Perchlorate is a naturally occurring inorganic anion used as a component of solid rocket fuel, explosives, and pyrotechnics. Sufficiently high perchlorate intakes can modify thyroid function by competitively inhibiting iodide uptake in adults; however little is known about perchlorate exposure and health effects in infants. Food intake models predict that infants have higher perchlorate exposure doses than adults. For this reason, we measured perchlorate and related anions (nitrate, thiocyanate, and iodide) in 206 urine samples from 92 infants ages 1–377 days and calculated perchlorate intake dose for this population of infants. The median estimated exposure dose for this population of infants was 0.160 μg/kg/day. Of the 205 individual dose estimates, 9% exceeded the reference dose of 0.7 μg/kg/day; 6% of infants providing multiple samples had multiple perchlorate dose estimates above the reference dose. Estimated exposure dose differed by feeding method: breast-fed infants had a higher perchlorate exposure dose (geometric mean 0.220 μg/kg/day) than infants consuming cow milk-based formula (geometric mean 0.103 μg/kg/day, p<0.0001) or soy-based formula (geometric mean 0.027 μg/kg/day, p<0.0001), consistent with dose estimates based on dietary intake data. The ability of perchlorate to block adequate iodide uptake by the thyroid may have been reduced by the iodine-sufficient status of the infants studied (median urinary iodide 125 μg/L). Further research is needed to see whether these perchlorate intake doses lead to any health effects. PMID:21449579

  9. Perchlorate exposure and dose estimates in infants.

    PubMed

    Valentín-Blasini, Liza; Blount, Benjamin C; Otero-Santos, Samaret; Cao, Yang; Bernbaum, Judy C; Rogan, Walter J

    2011-05-01

    Perchlorate is a naturally occurring inorganic anion used as a component of solid rocket fuel, explosives, and pyrotechnics. Sufficiently high perchlorate intakes can modify thyroid function by competitively inhibiting iodide uptake in adults; however, little is known about perchlorate exposure and health effects in infants. Food intake models predict that infants have higher perchlorate exposure doses than adults. For this reason, we measured perchlorate and related anions (nitrate, thiocyanate, and iodide) in 206 urine samples from 92 infants ages 1-377 days and calculated perchlorate intake dose for this sample of infants. The median estimated exposure dose for this sample of infants was 0.160 μg/kg/day. Of the 205 individual dose estimates, 9% exceeded the reference dose of 0.7 μg/kg/day; 6% of infants providing multiple samples had multiple perchlorate dose estimates above the reference dose. Estimated exposure dose differed by feeding method: breast-fed infants had a higher perchlorate exposure dose (geometric mean 0.220 μg/kg/day) than infants consuming cow milk-based formula (geometric mean 0.103 μg/kg/day, p < 0.0001) or soy-based formula (geometric mean 0.027 μg/kg/day, p < 0.0001), consistent with dose estimates based on dietary intake data. The ability of perchlorate to block adequate iodide uptake by the thyroid may have been reduced by the iodine-sufficient status of the infants studied (median urinary iodide 125 μg/L). Further research is needed to see whether these perchlorate intake doses lead to any health effects.

  10. 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.

  11. 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

  12. Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses.

    PubMed

    Vandenberg, Laura N; 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; Myers, John Peterson

    2012-06-01

    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

  13. Resource utilization. High dose rate versus low dose rate brachytherapy for gynecologic cancer.

    PubMed

    Bastin, K; Buchler, D; Stitt, J; Shanahan, T; Pola, Y; Paliwal, B; Kinsella, T

    1993-06-01

    A comparative analysis of anesthesia use, perioperative morbidity and mortality, capital, and treatment cost of high dose rate versus low dose rate intracavitary brachytherapy for gynecologic malignancy is presented. To assess current anesthesia utilization, application location, and high dose rate afterloader availability for gynecologic brachytherapy in private and academic practices, a nine-question survey was sent to 150 radiotherapy centers in the United States, of which 95 (63%) responded. Of these 95 respondents, 95% used low dose rate brachytherapy, and 18% possessed high dose rate capability. General anesthesia was used in 95% of programs for tandem + ovoid and in 31% for ovoids-only placement. Differences among private and academic practice respondents were minimal. In our institution, a cost comparison for low dose rate therapy (two applications with 3 hospital days per application, operating and recovery room use, spinal anesthesia, radiotherapy) versus high dose rate treatment (five outpatient departmental applications, intravenous anesthesia without an anesthesiologist, radiotherapy) revealed a 244% higher overall charge for low dose rate treatment, primarily due to hospital and operating room expenses. In addition to its ability to save thousands of dollars per intracavitary patient, high dose rate therapy generated a "cost-shift," increasing radiotherapy departmental billings by 438%. More importantly, perioperative morbidity and mortality in our experience of 500+ high dose rate applications compared favorably with recently reported data using low dose rate intracavitary treatment. Capital investment, maintenance requirements, and depreciation costs for high dose rate capability are reviewed. Application of the defined "revenue-cost ratio" formula demonstrates the importance of high application numbers and consistent reimbursement for parity in high dose rate operation. Logically, inadequate third-party reimbursement (e.g., Medicare) reduces high

  14. Optimal Dose of Vitamin D3 400 I.U. for Average Adults has A Significant Anti-Cancer Effect, While Widely Used 2000 I.U. or Higher Promotes Cancer: Marked Reduction of Taurine & 1α, 25(OH)2D3 Was Found In Various Cancer Tissues and Oral Intake of Optimal Dose of Taurine 175mg for Average Adults, Rather Than 500mg, Was Found to Be A New Potentially Safe and More Effective Method of Cancer Treatment.

    PubMed

    Omura, Yoshiaki; Lu, Dominic; Jones, Marilyn K; Nihrane, Abdallah; Duvvi, Harsha; Yapor, Dario; Shimotsuura, Yasuhiro; Ohki, Motomu

    2016-01-01

    During the past 10 years, the author had found that the optimal dose of Vitamin D3 400 I.U. has safe & effective anticancer effects, while commonly used 2000-5000 I.U. of Vit. D3 often creates a 2-3 time increase in cancer markers. We examined the concentration of Taurine in normal internal organs and in cancer using Bi-Digital O-Ring Test. We found that Taurine levels in normal tissue are 4-6ng. But, the amount of Taurine of average normal value of 5.0-5.25ng was strikingly reduced to 0.0025-0.0028ng in this study of several examples in adenocarcinomas of the esophagus, stomach, pancreas, colon, prostate, and lung, as well as breast cancer. The lowest Taurine levels of 0.0002-0.0005ng were found in so called Zika virus infected babies from Brazil with microcephaly. While Vitamin D3 receptor stimulant 1α, 25 (OH)2D3 in normal tissues was 0.45-0.53ng, they were reduced to 0.025-0.006ng in cancers (1/100th-1/200th of normal value), particularly in various adenocarcinomas. All of these adenocarcinomas had about 1500ng HPV-16 viral infection. In 500 breast cancers, about 97% had HPV-16. The optimal dose of Taurine for average adult has been found to be about 175mg, rather than the widely used 500mg. In addition, since Taurine is markedly reduced to close to 1/1000th-1/2000th of its normal value in these cancer tissues, we examined the effect of the optimal dose of Taurine on cancer patients. Optimal dose of Taurine produced a very significant decrease in cancer-associated parameters, such as Oncogene C-fosAb2 & Integrin α5β1 being reduced to less than 1/1,000th, and 8-OH-dG (which increases in the presence of DNA mutation) reduced to less than 1/10th. The optimal dose of Taurine 175mg for average adult various cancer patient 3 times a day alone provide beneficial effects with very significant anti-cancer effects with strikingly increased urinary excretion of bacteria, viruses, & funguses, asbestos, toxic metals & other toxic substances. However, optimal doses of

  15. Optimal Dose of Vitamin D3 400 I.U. for Average Adults has A Significant Anti-Cancer Effect, While Widely Used 2000 I.U. or Higher Promotes Cancer: Marked Reduction of Taurine & 1α, 25(OH)2D3 Was Found In Various Cancer Tissues and Oral Intake of Optimal Dose of Taurine 175mg for Average Adults, Rather Than 500mg, Was Found to Be A New Potentially Safe and More Effective Method of Cancer Treatment.

    PubMed

    Omura, Yoshiaki; Lu, Dominic; Jones, Marilyn K; Nihrane, Abdallah; Duvvi, Harsha; Yapor, Dario; Shimotsuura, Yasuhiro; Ohki, Motomu

    2016-01-01

    During the past 10 years, the author had found that the optimal dose of Vitamin D3 400 I.U. has safe & effective anticancer effects, while commonly used 2000-5000 I.U. of Vit. D3 often creates a 2-3 time increase in cancer markers. We examined the concentration of Taurine in normal internal organs and in cancer using Bi-Digital O-Ring Test. We found that Taurine levels in normal tissue are 4-6ng. But, the amount of Taurine of average normal value of 5.0-5.25ng was strikingly reduced to 0.0025-0.0028ng in this study of several examples in adenocarcinomas of the esophagus, stomach, pancreas, colon, prostate, and lung, as well as breast cancer. The lowest Taurine levels of 0.0002-0.0005ng were found in so called Zika virus infected babies from Brazil with microcephaly. While Vitamin D3 receptor stimulant 1α, 25 (OH)2D3 in normal tissues was 0.45-0.53ng, they were reduced to 0.025-0.006ng in cancers (1/100th-1/200th of normal value), particularly in various adenocarcinomas. All of these adenocarcinomas had about 1500ng HPV-16 viral infection. In 500 breast cancers, about 97% had HPV-16. The optimal dose of Taurine for average adult has been found to be about 175mg, rather than the widely used 500mg. In addition, since Taurine is markedly reduced to close to 1/1000th-1/2000th of its normal value in these cancer tissues, we examined the effect of the optimal dose of Taurine on cancer patients. Optimal dose of Taurine produced a very significant decrease in cancer-associated parameters, such as Oncogene C-fosAb2 & Integrin α5β1 being reduced to less than 1/1,000th, and 8-OH-dG (which increases in the presence of DNA mutation) reduced to less than 1/10th. The optimal dose of Taurine 175mg for average adult various cancer patient 3 times a day alone provide beneficial effects with very significant anti-cancer effects with strikingly increased urinary excretion of bacteria, viruses, & funguses, asbestos, toxic metals & other toxic substances. However, optimal doses of

  16. Occupational radiation doses during interventional procedures

    NASA Astrophysics Data System (ADS)

    Nuraeni, N.; Hiswara, E.; Kartikasari, D.; Waris, A.; Haryanto, F.

    2016-03-01

    Digital subtraction angiography (DSA) is a type of fluoroscopy technique used in interventional radiology to clearly visualize blood vessels in a bony or dense soft tissue environment. The use of DSA procedures has been increased quite significantly in the Radiology departments in various cities in Indonesia. Various reports showed that both patients and medical staff received a noticeable radiation dose during the course of this procedure. A study had been carried out to measure these doses among interventionalist, nurse and radiographer. The results show that the interventionalist and the nurse, who stood quite close to the X-ray beams compared with the radiographer, received radiation higher than the others. The results also showed that the radiation dose received by medical staff were var depending upon the duration and their position against the X-ray beams. Compared tothe dose limits, however, the radiation dose received by all these three medical staff were still lower than the limits.

  17. EXOMARS IRAS (DOSE) radiation measurements.

    NASA Astrophysics Data System (ADS)

    Federico, C.; Di Lellis, A. M.; Fonte, S.; Pauselli, C.; Reitz, G.; Beaujean, R.

    The characterization and the study of the radiations on their interaction with organic matter is of great interest in view of the human exploration on Mars. The Ionizing RAdiation Sensor (IRAS) selected in the frame of the ExoMars/Pasteur ESA mission is a lightweight particle spectrometer combining various techniques of radiation detection in space. It characterizes the first time the radiation environment on the Mars surface, and provide dose and dose equivalent rates as precursor information absolutely necessary to develop ways to mitigate the radiation risks for future human exploration on Mars. The Martian radiation levels are much higher than those found on Earth and they are relatively low for space. Measurements on the surface will show if they are similar or not to those seen in orbit (modified by the presence of ``albedo'' neutrons produced in the regolith and by the thin Martian atmosphere). IRAS consists of a telescope based on segmented silicon detectors of about 40\\userk\\milli\\metre\\user;k diameter and 300\\user;k\\micro\\metre\\user;k thickness, a segmented organic scintillator, and of a thermoluminescence dosimeter. The telescope will continuously monitor temporal variation of the particle count rate, the dose rate, particle and LET (Linear Energy Transfer) spectra. Tissue equivalent BC430 scintillator material will be used to measure the neutron dose. Neutrons are selected by a criteria requiring no signal in the anti-coincidence. Last, the passive thermoluminescence dosimeter, based on LiF:Mg detectors, regardless the on board operation timing, will measure the total dose accumulated during the exposure period and due to beta and gamma radiation, with a responsivity very close to that of a human tissue.

  18. Doses from radiation exposure.

    PubMed

    Menzel, H-G; Harrison, J D

    2012-01-01

    Practical implementation of the International Commission on Radiological Protection's (ICRP) system of protection requires the availability of appropriate methods and data. The work of Committee 2 is concerned with the development of reference data and methods for the assessment of internal and external radiation exposure of workers and members of the public. This involves the development of reference biokinetic and dosimetric models, reference anatomical models of the human body, and reference anatomical and physiological data. Following ICRP's 2007 Recommendations, Committee 2 has focused on the provision of new reference dose coefficients for external and internal exposure. As well as specifying changes to the radiation and tissue weighting factors used in the calculation of protection quantities, the 2007 Recommendations introduced the use of reference anatomical phantoms based on medical imaging data, requiring explicit sex averaging of male and female organ-equivalent doses in the calculation of effective dose. In preparation for the calculation of new dose coefficients, Committee 2 and its task groups have provided updated nuclear decay data (ICRP Publication 107) and adult reference computational phantoms (ICRP Publication 110). New dose coefficients for external exposures of workers are complete (ICRP Publication 116), and work is in progress on a series of reports on internal dose coefficients to workers from inhaled and ingested radionuclides. Reference phantoms for children will also be provided and used in the calculation of dose coefficients for public exposures. Committee 2 also has task groups on exposures to radiation in space and on the use of effective dose.

  19. Oncogenic transformation through the cell cycle and the LET dependent inverse dose rate effect

    NASA Technical Reports Server (NTRS)

    Geard, C. R.; Miller, R. C.; Brenner, D. J.; Hall, E. J.; Wachholz, B. W. (Principal Investigator)

    1994-01-01

    Synchronised populations of mouse C3H/10T-1/2 cells were obtained by a stringent mitotic dislodgment procedure. Mitotic cells rapidly attach and progress sequentially through the cell cycle. Irradiation (3 Gy of X rays) was carried out at intervals from 0 to 18 h after initiating cell cycle progression of the mitotic cells. Oncogenic transformation was enhanced 10-fold over cells irradiated soon after replating (G1 and S phases) for cells in a near 2 h period corresponding to cells in G2 phase but not in mitosis. The cell surviving fraction had a 2-1/2-fold variation with resistant peaks corresponding to the late G1 and late S phases. These findings provide experimental support for the hypothesis initiated by Rossi and Kellerer and developed by Brenner and Hall to explain the LET dependent inverse dose rate effect for oncogenic transformation.

  20. Total ionizing dose effects of domestic SiGe HBTs under different dose rates

    NASA Astrophysics Data System (ADS)

    Liu, Mo-Han; Lu, Wu; Ma, Wu-Ying; Wang, Xin; Guo, Qi; He, Cheng-Fa; Jiang, Ke; Li, Xiao-Long; Xun, Ming-Zhu

    2016-03-01

    The total ionizing radiation (TID) response of commercial NPN silicon germanium hetero-junction bipolar transistors (SiGe HBTs) produced domestically are investigated under dose rates of 800 mGy(Si)/s and 1.3 mGy(Si)/s with a Co-60 gamma irradiation source. The changes of transistor parameters such as Gummel characteristics, and excess base current before and after irradiation, are examined. The results of the experiments show that for the KT1151, the radiation damage is slightly different under the different dose rates after prolonged annealing, and shows a time dependent effect (TDE). For the KT9041, however, the degradations of low dose rate irradiation is higher than for the high dose rate, demonstrating that there is a potential enhanced low dose rate sensitivity (ELDRS) effect for the KT9041. The possible underlying physical mechanisms of the different dose rates responses induced by the gamma rays are discussed.

  1. Dose Effects of Ion Beam Exposure on Deinococcus Radiodurans: Survival and Dose Response

    NASA Astrophysics Data System (ADS)

    Song, Dao-jun; Wu, Li-fang; Wu, Li-jun; Yu, Zeng-liang

    2001-02-01

    To explore the survival and dose response of organism for different radiation sources is of great importance in the research of radiobiology. In this study, the survival-dose response of Deinococcus radiodurans (E.coli, as the control) for ultra-violet (UV), γ-rays radiation and ion beam exposure was investigated. The shoulder type of survival curves were found for both UV and γ-ray ionizing radiation, but the saddle type of survival curves were shown for H+, N+(20keV and 30keV) and Ar+ beam exposure. This dose effect of the survival initially decreased with the increase in dose and then increased in the high dose range and finally decreased again in the higher dose range. Our experimental results suggest that D. radiodurans, which is considerably radio-resistant to UV and x-ray and γ-ray ionizing radiation, do not resist ion beam exposure.

  2. Implications of dose-dependent target tissue absorption for linear and non-linear/threshold approaches in development of a cancer-based oral toxicity factor for hexavalent chromium.

    PubMed

    Haney, J

    2015-07-01

    Dose-dependent changes in target tissue absorption have important implications for determining the most defensible approach for developing a cancer-based oral toxicity factor for hexavalent chromium (CrVI). For example, mouse target tissue absorption per unit dose is an estimated 10-fold lower at the CrVI dose corresponding to the federal maximum contaminant level (MCL) than at the USEPA draft oral slope factor (SFo) point of departure dose. This decreasing target tissue absorption as doses decrease to lower, more environmentally-relevant doses is inconsistent with linear low-dose extrapolation. The shape of the dose-response curve accounting for this toxicokinetic phenomenon would clearly be non-linear. Furthermore, these dose-dependent differences in absorption indicate that the magnitude of risk overestimation by a linear low-dose extrapolation approach (e.g., SFo) increases and is likely to span one or perhaps more orders of magnitude as it is used to predict risk at progressively lower, more environmentally-relevant doses. An additional apparent implication is that no single SFo can reliably predict risk across potential environmental doses (e.g., doses corresponding to water concentrations⩽the federal MCL). A non-linear approach, consistent with available mode of action data, is most scientifically defensible for derivation of an oral toxicity factor for CrVI-induced carcinogenesis.

  3. Independent dose calculations for commissioning, quality assurance and dose reconstruction of PBS proton therapy

    NASA Astrophysics Data System (ADS)

    Meier, G.; Besson, R.; Nanz, A.; Safai, S.; Lomax, A. J.

    2015-04-01

    Pencil beam scanning proton therapy allows the delivery of highly conformal dose distributions by delivering several thousand pencil beams. These beams have to be individually optimised and accurately delivered requiring a significant quality assurance workload. In this work we describe a toolkit for independent dose calculations developed at Paul Scherrer Institut which allows for dose reconstructions at several points in the treatment workflow. Quality assurance based on reconstructed dose distributions was shown to be favourable to pencil beam by pencil beam comparisons for the detection of delivery uncertainties and estimation of their effects. Furthermore the dose reconstructions were shown to have a sensitivity of the order of or higher than the measurements currently employed in the clinical verification procedures. The design of the independent dose calculation tool allows for a high modifiability of the dose calculation parameters (e.g. depth dose profiles, angular spatial distributions) allowing for a safe environment outside of the clinical treatment planning system for investigating the effect of such parameters on the resulting dose distributions and thus distinguishing between different contributions to measured dose deviations. The presented system could potentially reduce the amount of patient-specific quality assurance measurements which currently constitute a bottleneck in the clinical workflow.

  4. Ir-192 HDR transit dose and radial dose function determination using alanine/EPR dosimetry

    NASA Astrophysics Data System (ADS)

    Guzmán Calcina, Carmen S.; de Almeida, Adelaide; Oliveira Rocha, José R.; Abrego, Felipe Chen; Baffa, Oswaldo

    2005-03-01

    Source positioning close to the tumour in high dose rate (HDR) brachytherapy is not instantaneous. An increment of dose will be delivered during the movement of the source in the trajectory to its static position. This increment is the transit dose, often not taken into account in brachytherapeutic treatment planning. The transit dose depends on the prescribed dose, number of treatment fractions, velocity and activity of the source. Combining all these factors, the transit dose can be 5% higher than the prescribed absorbed dose value (Sang-Hyun and Muller-Runkel, 1994 Phys. Med. Biol. 39 1181 8, Nath et al 1995 Med. Phys. 22 209 34). However, it cannot exceed this percentage (Nath et al 1995). In this work, we use the alanine-EPR (electron paramagnetic resonance) dosimetric system using analysis of the first derivative of the signal. The transit dose was evaluated for an HDR system and is consistent with that already presented for TLD dosimeters (Bastin et al 1993 Int. J. Radiat. Oncol. Biol. Phys. 26 695 702). Also using the same dosimetric system, the radial dose function, used to evaluate the geometric dose degradation around the source, was determined and its behaviour agrees better with those obtained by Monte Carlo simulations (Nath et al 1995, Williamson and Nath 1991 Med. Phys. 18 434 48, Ballester et al 1997 Med. Phys. 24 1221 8, Ballester et al 2001 Phys. Med. Biol. 46 N79 90) than with TLD measurements (Nath et al 1990 Med. Phys. 17 1032 40).

  5. Independent dose calculations for commissioning, quality assurance and dose reconstruction of PBS proton therapy.

    PubMed

    Meier, G; Besson, R; Nanz, A; Safai, S; Lomax, A J

    2015-04-01

    Pencil beam scanning proton therapy allows the delivery of highly conformal dose distributions by delivering several thousand pencil beams. These beams have to be individually optimised and accurately delivered requiring a significant quality assurance workload. In this work we describe a toolkit for independent dose calculations developed at Paul Scherrer Institut which allows for dose reconstructions at several points in the treatment workflow. Quality assurance based on reconstructed dose distributions was shown to be favourable to pencil beam by pencil beam comparisons for the detection of delivery uncertainties and estimation of their effects. Furthermore the dose reconstructions were shown to have a sensitivity of the order of or higher than the measurements currently employed in the clinical verification procedures. The design of the independent dose calculation tool allows for a high modifiability of the dose calculation parameters (e.g. depth dose profiles, angular spatial distributions) allowing for a safe environment outside of the clinical treatment planning system for investigating the effect of such parameters on the resulting dose distributions and thus distinguishing between different contributions to measured dose deviations. The presented system could potentially reduce the amount of patient-specific quality assurance measurements which currently constitute a bottleneck in the clinical workflow. PMID:25779992

  6. Single-dose versus multi-dose vaccine vials for immunization programmes in developing countries.

    PubMed Central

    Drain, Paul K.; Nelson, Carib M.; Lloyd, John S.

    2003-01-01

    Excessive vaccine wastage and safety concerns have prompted the international health community to develop and supply vaccines in formats other than the standard multi-dose vial. This article presents a programmatic and economic comparison of the major differences between the multi-dose vials and single-dose formats used for immunization services in developing countries. Multi-dose vials, in general, sell at a lower per-dose price and occupy less cold-chain capacity than single-dose formats. However, higher wastage rates may offset these benefits, especially for more expensive vaccines. Single-dose formats offer several important programmatic benefits, such as increased vaccination opportunities and improved vaccine safety. One single-dose format, the prefilled auto-disable (AD) device, provides additional injection safety and convenience features because it physically combines the vaccine and AD syringe. Selecting the appropriate vaccine presentation will depend on many factors. However, multi-dose vials are likely to be most appropriate for cheaper vaccines and in settings where cold-chain storage capacity is restricted. Single-dose formats will be most appropriate for more expensive vaccines and where there are problems with unsafe injection practices. Prefilled AD injection devices will be particularly useful in expanding outreach services while eliminating the possibility of needle reuse. PMID:14758432

  7. Synchronized dynamic dose reconstruction

    SciTech Connect

    Litzenberg, Dale W.; Hadley, Scott W.; Tyagi, Neelam; Balter, James M.; Ten Haken, Randall K.; Chetty, Indrin J.

    2007-01-15

    Variations in target volume position between and during treatment fractions can lead to measurable differences in the dose distribution delivered to each patient. Current methods to estimate the ongoing cumulative delivered dose distribution make idealized assumptions about individual patient motion based on average motions observed in a population of patients. In the delivery of intensity modulated radiation therapy (IMRT) with a multi-leaf collimator (MLC), errors are introduced in both the implementation and delivery processes. In addition, target motion and MLC motion can lead to dosimetric errors from interplay effects. All of these effects may be of clinical importance. Here we present a method to compute delivered dose distributions for each treatment beam and fraction, which explicitly incorporates synchronized real-time patient motion data and real-time fluence and machine configuration data. This synchronized dynamic dose reconstruction method properly accounts for the two primary classes of errors that arise from delivering IMRT with an MLC: (a) Interplay errors between target volume motion and MLC motion, and (b) Implementation errors, such as dropped segments, dose over/under shoot, faulty leaf motors, tongue-and-groove effect, rounded leaf ends, and communications delays. These reconstructed dose fractions can then be combined to produce high-quality determinations of the dose distribution actually received to date, from which individualized adaptive treatment strategies can be determined.

  8. Oxymetazoline Metered Dose Spray: Factors Affecting Delivery Volume

    PubMed Central

    Walia, Hina; Rafiq, Mahmood; Grannell, Timothy; Cartabuke, Richard S.; Tobias, Joseph D.

    2016-01-01

    OBJECTIVES: The current study compared the amount of oxymetazoline delivered by various anesthesia providers when holding the bottle in the upright and inverted position. Additionally, the amount delivered from a full bottle and a half-full bottle was also investigated. METHODS: Using an analytical balance that was calibrated to zero, we evaluated the impact the position of the bottle and the volume of oxymetazoline in the bottle had on the amount being delivered by both anesthesia staff and trainees. RESULTS: When using both filled and half-filled bottles, the amount delivered increased significantly when comparing the upright versus inverted position. With a full bottle, the amount delivered when the bottle was inverted increased almost 10-fold from 62 ± 80 to 606 ± 366 μL (p < 0.0001). Similarly, even with a half-filled bottle, the amount delivered increased in the inverted positions from 41 ± 48 to 645 ± 393 μL. Regardless of the scenario, we also noted significant variation from provider to provider. CONCLUSIONS: Our results demonstrate that several factors may affect the amount of oxymetazoline delivered for metered dose bottles. Given the potential for severe end-organ effects with excessive dosage, alternative means of delivery are needed for its perioperative use. PMID:27453703

  9. Calculating drug doses.

    PubMed

    2016-09-01

    Numeracy and calculation are key skills for nurses. As nurses are directly accountable for ensuring medicines are prescribed, dispensed and administered safely, they must be able to understand and calculate drug doses. PMID:27615351

  10. Ibuprofen dosing for children

    MedlinePlus

    Motrin; Advil ... Ibuprofen is a type of nonsteroidal anti-inflammatory drug (NSAID). It can help: Reduce aches, pain, sore ... Ibuprofen can be taken as liquid or chewable tablets. To give the correct dose, you need to ...

  11. Higher Education Exchange, 2012

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    2012-01-01

    "Higher Education Exchange" publishes case studies, analyses, news, and ideas about efforts within higher education to develop more democratic societies. Contributors to this issue of the "Higher Education Exchange" examine whether institutions of higher learning are doing anything to increase the capacity of citizens to shape their future.…

  12. Higher Education Exchange, 2010

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    2010-01-01

    "Higher Education Exchange" publishes case studies, analyses, news, and ideas about efforts within higher education to develop more democratic societies. Contributors to this issue of the "Higher Education Exchange" examine whether institutions of higher learning are doing anything to increase the capacity of citizens to shape their future.…

  13. Higher Education Exchange, 2008

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    2008-01-01

    "Higher Education Exchange" publishes case studies, analyses, news, and ideas about efforts within higher education to develop more democratic societies. Contributors to this issue of the "Higher Education Exchange" examine whether institutions of higher learning are doing anything to increase the capacity of citizens to shape their future.…

  14. Higher Education Exchange, 2014

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    2014-01-01

    Research shows that not only does higher education not see the public; when the public, in turn, looks at higher education, it sees mostly malaise, inefficiencies, expense, and unfulfilled promises. Yet, the contributors to this issue of the "Higher Education Exchange" tell of bright spots in higher education where experiments in working…

  15. Higher Education Exchange, 2004

    ERIC Educational Resources Information Center

    Brown, David W., Ed; Witte, Deborah, Ed.

    2004-01-01

    The Higher Education Exchange is part of a movement to strengthen higher education's democratic mission and foster a more democratic culture throughout American society. Working in this tradition, the Higher Education Exchange publishes case studies, analyses, news, and ideas about efforts within higher education to develop more democratic…

  16. Higher Education Exchange, 2005

    ERIC Educational Resources Information Center

    Brown, David W., Ed; Witte, Deborah, Ed.

    2005-01-01

    The "Higher Education Exchange" is part of a movement to strengthen higher education's democratic mission and foster a more democratic culture throughout American society. Working in this tradition, the "Higher Education Exchange" publishes case studies, analyses, news, and ideas about efforts within higher education to develop more democratic…

  17. Higher Education Exchange, 2011

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    2011-01-01

    "Higher Education Exchange" publishes case studies, analyses, news, and ideas about efforts within higher education to develop more democratic societies. Contributors to this issue of the "Higher Education Exchange" examine whether institutions of higher learning are doing anything to increase the capacity of citizens to shape their future.…

  18. Sampling and recording dose rate meter

    SciTech Connect

    Kronenberg, S.

    1984-04-06

    A wide range radiation dose rate for civil defense use, including a Geiger-Mueller tube used in a continuous counting mode and for measuring dose rates from the natural background to about 30. rads/hr., with an ion chamber arranged to measure higher dose rates up to 10,000 rads/hr. The instrument has a sample and record capability in which the selected radiation detector will have its output connected to a selected storage capacitor for a precise interval of time determined by a timing circuit and the storage capacitor will accumulate and hold a voltage proportional to the dose rate, which can be read by means of an electrometer at a later time. The instrument has a self contained hand cranked power supply and all components are selected for long shelf life.

  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. The Higher Education Enterprise.

    ERIC Educational Resources Information Center

    Ottinger, Cecilia A.

    1991-01-01

    Higher education not only contributes to the development of the human resources and intellectual betterment of the nation but is also a major economic enterprise. This research brief reviews and highlights data on the size and growth of higher education and illustrates how higher education institutions are preparing the future labor force. It…

  1. Reflections on "Higher Education"

    ERIC Educational Resources Information Center

    Gilbert, Felix

    1974-01-01

    The elitist, professional, and philosophical elements of higher education are reflected upon with stress on the differences between higher education and higher learning, where education is concerned with giving wider groups a share in a broad image of man, and learning is concerned with increasing specialization. (JH)

  2. Dose reconstruction for intensity-modulated radiation therapy using a non-iterative method and portal dose image

    NASA Astrophysics Data System (ADS)

    Yeo, Inhwan Jason; Jung, Jae Won; Chew, Meng; Kim, Jong Oh; Wang, Brian; Di Biase, Steven; Zhu, Yunping; Lee, Dohyung

    2009-09-01

    A straightforward and accurate method was developed to verify the delivery of intensity-modulated radiation therapy (IMRT) and to reconstruct the dose in a patient. The method is based on a computational algorithm that linearly describes the physical relationship between beamlets and dose-scoring voxels in a patient and the dose image from an electronic portal imaging device (EPID). The relationship is expressed in the form of dose response functions (responses) that are quantified using Monte Carlo (MC) particle transport techniques. From the dose information measured by the EPID the received patient dose is reconstructed by inversely solving the algorithm. The unique and novel non-iterative feature of this algorithm sets it apart from many existing dose reconstruction methods in the literature. This study presents the algorithm in detail and validates it experimentally for open and IMRT fields. Responses were first calculated for each beamlet of the selected fields by MC simulation. In-phantom and exit film dosimetry were performed on a flat phantom. Using the calculated responses and the algorithm, the exit film dose was used to inversely reconstruct the in-phantom dose, which was then compared with the measured in-phantom dose. The dose comparison in the phantom for all irradiated fields showed a pass rate of higher than 90% dose points given the criteria of dose difference of 3% and distance to agreement of 3 mm.

  3. 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.

  4. Dose Calculation Spreadsheet

    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 atmore » various downwind distances as specified by the user.« less

  5. Radiation dose descriptors: BERT, COD, DAP, and other strange creatures.

    PubMed

    Nickoloff, Edward L; Lu, Zheng Feng; Dutta, Ajoy K; So, James C

    2008-01-01

    Over the years, a number of terms have been used to describe radiation dose. Eight common radiation dose descriptors include background equivalent radiation time (BERT), critical organ dose (COD), surface absorbed dose (SAD), dose area product (DAP), diagnostic acceptable reference level (DARLing), effective dose (ED), fetal absorbed dose (FAD), and total imparted energy (TIE). BERT is compared to the annual natural background radiation (about 3 mSv per year) and is easily understandable for the general public. COD refers to the radiation dose delivered to an individual critical organ. SAD is the radiation dose delivered at the skin surface. DAP is a product of the irradiated surface area multiplied by the radiation dose at the surface. DARLing is usually the radiation level that encompasses 75% (the third quartile) of the data derived from a nationwide or regional survey. DARLings are meant for voluntary guidance. Consistently higher patient doses should be investigated for possible equipment deficiencies or suboptimal protocols. ED is obtained by multiplying the radiation dose delivered to each organ by its weighting factor and then by adding those values to get the sum. It can be used to assess the risk of radiation-induced cancers and serious hereditary effects to future generations, regardless of the procedure being performed, and is the most useful radiation dose descriptor. FAD is the radiation dose delivered to the fetus, and TIE is the sum of the energy imparted to all irradiated tissue. Each of these descriptors is intended to relate radiation dose ultimately to potential biologic effects. To avoid confusion, the key is to avoid using the terms interchangeably. It is important to understand each of the radiation dose descriptors and their derivation in order to correctly evaluate radiation dose and to consult with patients concerned about the risks of radiation.

  6. Single-neuron axonal pathfinding under geometric guidance: low-dose-methylmercury developmental neurotoxicity test.

    PubMed

    Wei, Lina; Sweeney, Andrew J; Sheng, Liyuan; Fang, Yu; Kindy, Mark S; Xi, Tingfei; Gao, Bruce Z

    2014-09-21

    Because the nervous system is most vulnerable to toxicants during development, there is a crucial need for a highly sensitive developmental-neurotoxicity-test model to detect potential toxicants at low doses. We developed a lab-on-chip wherein single-neuron axonal pathfinding under geometric guidance was created using soft lithography and laser cell-micropatterning techniques. After coating the surface with L1, an axon-specific member of the Ig family of cell adhesion molecules (CAMs), and optimizing microunit geometric parameters, we introduced low-dose methylmercury, a well-known, environmentally significant neurotoxicant, in the shared medium. Its developmental neurotoxicity was evaluated using a novel axonal pathfinding assay including axonal turning and branching rates at turning points in this model. Compared to the conventional neurite-outgrowth assay, this model's detection threshold for low-dose methylmercury was 10-fold more sensitive at comparable exposure durations. These preliminary results support study of developmental effects of known and potential neurotoxicants on axon pathfinding. This novel assay model would be useful to study neuronal disease mechanisms at the single-cell level. To our knowledge, the potential of methylmercury chloride to cause acute in vitro developmental neurotoxicity (DNT) at such a low dosage has not been reported. This is the first DNT test model with high reproducibility to use single-neuron axonal pathfinding under precise geometric guidance. PMID:25041816

  7. Pain and Mean Absorbed Dose to the Pubic Bone After Radiotherapy Among Gynecological Cancer Survivors

    SciTech Connect

    Waldenstroem, Ann-Charlotte; Olsson, Caroline; Wilderaeng, Ulrica; Dunberger, Gail; Lind, Helena; Al-Abany, Massoud; Palm, Asa; Avall-Lundqvist, Elisabeth; Johansson, Karl-Axel; Steineck, Gunnar

    2011-07-15

    Purpose: To analyze the relationship between mean absorbed dose to the pubic bone after pelvic radiotherapy for gynecological cancer and occurrence of pubic bone pain among long-term survivors. Methods and Materials: In an unselected, population-based study, we identified 823 long-term gynecological cancer survivors treated with pelvic radiotherapy during 1991-2003. For comparison, we used a non-radiation-treated control population of 478 matched women from the Swedish Population Register. Pain, intensity of pain, and functional impairment due to pain in the pubic bone were assessed with a study-specific postal questionnaire. Results: We analyzed data from 650 survivors (participation rate 79%) with median follow-up of 6.3 years (range, 2.3-15.0 years) along with 344 control women (participation rate, 72 %). Ten percent of the survivors were treated with radiotherapy; ninety percent with surgery plus radiotherapy. Brachytherapy was added in 81%. Complete treatment records were recovered for 538/650 survivors, with dose distribution data including dose-volume histograms over the pubic bone. Pubic bone pain was reported by 73 survivors (11%); 59/517 (11%) had been exposed to mean absorbed external beam doses <52.5 Gy to the pubic bone and 5/12 (42%) to mean absorbed external beam doses {>=}52.5 Gy. Thirty-three survivors reported pain affecting sleep, a 13-fold increased prevalence compared with control women. Forty-nine survivors reported functional impairment measured as pain walking indoors, a 10-fold increased prevalence. Conclusions: Mean absorbed external beam dose above 52.5 Gy to the pubic bone increases the occurrence of pain in the pubic bone and may affect daily life of long-term survivors treated with radiotherapy for gynecological cancer.

  8. Single daily dosing of gentamicin: pharmacokinetic comparison of two dosing methodologies for postpartum endometritis.

    PubMed Central

    Liu, C; Abate, B; Reyes, M; Gonik, B

    1999-01-01

    OBJECTIVE: We compared the pharmacokinetics of two methods for dosing gentamicin for the treatment of postpartum endometritis with the goal of achieving adequate peak serum concentrations (>12 mg/L) and prolonged trough levels below 2 mg/L. METHODS: Group-I subjects (n = 5) received intravenous gentamicin, 5 mg/kg per total body weight over 60 min., with a maximum dose of 500 mg. Group-II subjects (n = 17) were dosed intravenously according to the following formula: Dose = desired peak concentration (fixed at 14 mg/L) * (volume of distribution, i.e., 0.35 L/kg) * adjusted body weight (in kilograms). Serum gentamicin levels were obtained 1 hr. and 8-12 hr. after infusion of the second dose. Pharmacokinetic parameters for the subjects in each group were calculated according to standard formulas. RESULTS: Subjects in Group I had significantly higher doses and peak drug concentrations (P < 0.01), while in Group II, 76% of patients had peak levels less than desired (<12 mg/L). Both groups maintained trough levels of <2 mg/L in excess of 12 hr. CONCLUSIONS: Changing to the adjusted body weight formula for Group I, while maintaining a dose between 4 and 5 mg/kg, would reduce excessive peak concentrations. Using a calculated volume of distribution of 0.4 L/kg in Group II would improve peak serum concentrations to the desired levels. Both dosing regimens ensure adequate aminoglycoside pharmacokinetic parameters and avoid the need for monitoring serial serum drug concentrations, provided the expected clinical response is also achieved. While the first dosing formula is simpler to calculate, the second dosing formula allows for more individualized dosing considerations. PMID:10371471

  9. LADTAPXL Aqueous Dose Spreadsheet

    SciTech Connect

    Hamby, David M.; Simpkins, Ali A.; Jannik, G. T.

    1999-08-10

    LADTAPXL is an EXCEL spreadsheet model of the NRC computer code LADTAP. LADTAPXL calculates maximally exposed individual and population doses from chronic liquid releases. Environmental pathways include external exposure resulting from recreational activities on the Savannah River and ingestion of water, fish, and invertebrates of Savannah River origin.

  10. 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)

  11. 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...

  12. OCCUPATIONAL DOSE ASSESSMENT IN INTERVENTIONAL CARDIOLOGY IN SERBIA.

    PubMed

    Kaljevic, J; Ciraj-Bjelac, O; Stankovic, J; Arandjic, D; Bozovic, P; Antic, V

    2016-09-01

    The objective of this work is to assess the occupational dose in interventional cardiology in a large hospital in Belgrade, Serbia. A double-dosimetry method was applied for the estimation of whole-body dose, using thermoluminescent dosemeters, calibrated in terms of the personal dose equivalent Hp(10). Besides the double-dosimetry method, eye dose was also estimated by means of measuring ambient dose equivalent, H*(10), and doses per procedure were reported. Doses were assessed for 13 physicians, 6 nurses and 10 radiographers, for 2 consequent years. The maximum annual effective dose assessed was 4.3, 2.1 and 1.3 mSv for physicians, nurses and radiographers, respectively. The maximum doses recorded by the dosemeter worn at the collar level (over the apron) were 16.8, 11.9 and 4.5 mSv, respectively. This value was used for the eye lens dose assessment. Estimated doses are in accordance with or higher than annual dose limits for the occupational exposure. PMID:26464526

  13. Ingestion of Nevada Test Site Fallout: Internal dose estimates

    SciTech Connect

    Whicker, F.W.; Kirchner, T.B.; Anspaugh, L.R.

    1996-10-01

    This paper summarizes individual and collective dose estimates for the internal organs of hypothetical yet representative residents of selected communities that received measurable fallout from nuclear detonations at the Nevada Test Site. The doses, which resulted from ingestion of local and regional food products contaminated with over 20 radionuclides, were estimated with use of the PATHWAY food-chain-transport model to provide estimates of central tendency and uncertainty. The thyroid gland received much higher doses than other internal organs and tissues. In a avery few cases, infants might have received thyroid doses in excess of 1 Gy, depending on location, diet, and timing of fallout. {sup 131}I was the primary thyroid dose contributor, and fresh milk was the main exposure pathway. With the exception of the thyroid, organ doses from the ingestion pathway were much smaller (<3%) than those from external gamma exposure to deposited fallout. Doses to residents living closest to the Nevada Test Site were contributed mainly by a few fallout events; doses to more distantly located people were generally smaller, but a greater number of events provided measurable contributions. The effectiveness of different fallout events in producing internal organ doses through ingestion varied dramatically with seasonal timing of the test, with maximum dose per unit fallout occurring for early summer depositions when milk cows were on pasture and fresh, local vegetables were used. Within specific communities, internal doses differed by age, sex, and lifestyle. Collective internal dose estimates for specific geographic areas are provided.

  14. Uncertainties on lung doses from inhaled plutonium.

    PubMed

    Puncher, Matthew; Birchall, Alan; Bull, Richard K

    2011-10-01

    In a recent epidemiological study, Bayesian uncertainties on lung doses have been calculated to determine lung cancer risk from occupational exposures to plutonium. These calculations used a revised version of the Human Respiratory Tract Model (HRTM) published by the ICRP. In addition to the Bayesian analyses, which give probability distributions of doses, point estimates of doses (single estimates without uncertainty) were also provided for that study using the existing HRTM as it is described in ICRP Publication 66; these are to be used in a preliminary analysis of risk. To infer the differences between the point estimates and Bayesian uncertainty analyses, this paper applies the methodology to former workers of the United Kingdom Atomic Energy Authority (UKAEA), who constituted a subset of the study cohort. The resulting probability distributions of lung doses are compared with the point estimates obtained for each worker. It is shown that mean posterior lung doses are around two- to fourfold higher than point estimates and that uncertainties on doses vary over a wide range, greater than two orders of magnitude for some lung tissues. In addition, we demonstrate that uncertainties on the parameter values, rather than the model structure, are largely responsible for these effects. Of these it appears to be the parameters describing absorption from the lungs to blood that have the greatest impact on estimates of lung doses from urine bioassay. Therefore, accurate determination of the chemical form of inhaled plutonium and the absorption parameter values for these materials is important for obtaining reliable estimates of lung doses and hence risk from occupational exposures to plutonium.

  15. Radiotherapy alone in breast cancer. I. Analysis of tumor parameters, tumor dose and local control: the experience of the Gustave-Roussy Institute and the Princess Margaret Hospital

    SciTech Connect

    Arriagada, R.; Mouriesse, H.; Sarrazin, D.; Clark, R.M.; Deboer, G.

    1985-10-01

    This retrospective study involved 463 breast cancer patients treated by radiotherapy alone at the Princess Margaret Hospital and at the Institut Gustave-Roussy. These patients either had operable tumors, but were unfit for general anesthesia, or had inoperable tumors due to local contraindications to surgery. Results were analyzed according to tumor response, local recurrence rate, tumor size, tumor fixation, nodal fixation and tumor dose. Conventional statistical analysis of local control showed two significant factors: tumor dose and tumor size. Multivariate analysis permitted to define an ''individual risk'' (IR) of local recurrence according to three independent factors: tumor size, tumor fixation, and nodal fixation. It was shown that the IR was a good prognostic factor for local control. Increase in tumor dose gave a similar effect in the local recurrence relative risk for all the IR groups. According to the slope of the dose-effect curve, it was deduced that a dose increase of 15 Gy can decrease the relative risk of local recurrence 2-fold. In fact, it was shown that tumor dose was the most significant independent factor on local control, able to produce up to a 10-fold increase compared to 2-fold decrease for tumor size. If the IR of local recurrence is known, a theoretical predictive value on local control, taking into account the tumor dose, can be determined according to the present data.

  16. Effects of Proton Radiation Dose, Dose Rate and Dose Fractionation on Hematopoietic Cells in Mice

    PubMed Central

    Ware, J. H.; Sanzari, J.; Avery, S.; Sayers, C.; Krigsfeld, G.; Nuth, M.; Wan, X. S.; Rusek, A.; Kennedy, A. R.

    2012-01-01

    The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05–0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals were used as controls. The results demonstrate a dose-dependent loss of white blood cells (WBCs) and lymphocytes by up to 61% and 72%, respectively, in mice irradiated with protons at doses up to 2 Gy. The results also demonstrate that the dose rate, fractionation pattern and energy of the proton radiation did not have significant effects on WBC and lymphocyte counts in the irradiated animals. These results suggest that the acute effects of proton radiation on WBC and lymphocyte counts are determined mainly by the radiation dose, with very little contribution from the dose rate (over the range of dose rates evaluated), fractionation and energy of the protons. PMID:20726731

  17. Effects of proton radiation dose, dose rate and dose fractionation on hematopoietic cells in mice

    SciTech Connect

    Ware, J.H.; Rusek, A.; Sanzari, J.; Avery, S.; Sayers, C.; Krigsfeld, G.; Nuth, M.; Wan, X.S.; Kennedy, A.R.

    2010-09-01

    The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05-0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals were used as controls. The results demonstrate a dose-dependent loss of white blood cells (WBCs) and lymphocytes by up to 61% and 72%, respectively, in mice irradiated with protons at doses up to 2 Gy. The results also demonstrate that the dose rate, fractionation pattern and energy of the proton radiation did not have significant effects on WBC and lymphocyte counts in the irradiated animals. These results suggest that the acute effects of proton radiation on WBC and lymphocyte counts are determined mainly by the radiation dose, with very little contribution from the dose rate (over the range of dose rates evaluated), fractionation and energy of the protons.

  18. Higher Education in Virginia.

    ERIC Educational Resources Information Center

    Virginia State Council of Higher Education, Richmond.

    For the past 7 years, the State Council of Higher Education has published a report of selected characteristics and degree programs for Virginia's state-supported colleges and universities. By combining data from independent institutions with information collected from the state-supported colleges, a more comprehensive picture of higher education…

  19. Minorities in Higher Education.

    ERIC Educational Resources Information Center

    Justiz, Manuel J., Ed.; And Others

    This book presents 19 papers on efforts to increase the participation of members of minority groups in higher education. The papers are: (1) "Demographic Trends and the Challenges to American Higher Education" (Manuel Justiz); (2) "Three Realities: Minority Life in the United States--The Struggle for Economic Equity (adapted by Don M. Blandin);…

  20. Hypermedia and Higher Education.

    ERIC Educational Resources Information Center

    Lemke, Jay L.

    1993-01-01

    Discusses changes in higher education that are resulting from the use of hypermedia. Topics addressed include the structure of traditional texts; a distributed model for academic communication; independent learning as a model for higher education; skills for hypermedia literacy; database searching; information retrieval; authoring skills; design…

  1. Reinventing Higher Education

    ERIC Educational Resources Information Center

    Hayes, Dianne

    2012-01-01

    Higher education institutions are in the battle of a lifetime as they are coping with political and economic uncertainties, threats to federal aid, declining state support, higher tuition rates and increased competition from for-profit institutions. Amid all these challenges, these institutions are pressed to keep up with technological demands,…

  2. Higher Education Exchange

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    2009-01-01

    This volume begins with an essay by Noelle McAfee, a contributor who is familiar to readers of Higher Education Exchange (HEX). She reiterates Mathews' argument regarding the disconnect between higher education's sense of engagement and the public's sense of engagement, and suggests a way around the epistemological conundrum of "knowledge produced…

  3. Higher Education Exchange, 2009

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    2009-01-01

    This volume begins with an essay by Noelle McAfee, a contributor who is familiar to readers of Higher Education Exchange (HEX). She reiterates Kettering's president David Mathews' argument regarding the disconnect between higher education's sense of engagement and the public's sense of engagement, and suggests a way around the epistemological…

  4. PHOENIX. Higher Wage Careers.

    ERIC Educational Resources Information Center

    Bismarck State Coll., ND.

    This document outlines the curriculum plan for the one-semester vocational-technical training component of PHOENIX: A Model Program for Higher-Wage Potential Careers offered by Bismarck State College (North Dakota) which prepares and/or retrains individuals for higher-wage technical careers. The comprehensive model for the program is organized…

  5. Higher Education Exchange 2006

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    2006-01-01

    Contributors to this issue of the Higher Education Exchange debate the issues around knowledge production, discuss the acquisition of deliberative skills for democracy, and examine how higher education prepares, or does not prepare, students for citizenship roles. Articles include: (1) "Foreword" (Deborah Witte); (2) "Knowledge, Judgment and…

  6. Reimagining Christian Higher Education

    ERIC Educational Resources Information Center

    Hulme, E. Eileen; Groom, David E., Jr.; Heltzel, Joseph M.

    2016-01-01

    The challenges facing higher education continue to mount. The shifting of the U.S. ethnic and racial demographics, the proliferation of advanced digital technologies and data, and the move from traditional degrees to continuous learning platforms have created an unstable environment to which Christian higher education must adapt in order to remain…

  7. Gender and Higher Education

    ERIC Educational Resources Information Center

    Bank, Barbara J., Ed.

    2011-01-01

    This comprehensive, encyclopedic review explores gender and its impact on American higher education across historical and cultural contexts. Challenging recent claims that gender inequities in U.S. higher education no longer exist, the contributors--leading experts in the field--reveal the many ways in which gender is embedded in the educational…

  8. Low-Dose Radioactive Iodine Destroys Thyroid Tissue Left after Surgery

    Cancer.gov

    A low dose of radioactive iodine given after surgery for thyroid cancer destroyed (ablated) residual thyroid tissue as effectively as a higher dose, with fewer side effects and less exposure to radiation, according to two randomized controlled trials.

  9. Absorbed dose water calorimeter

    SciTech Connect

    Domen, S.R.

    1982-01-26

    An absorbed dose water calorimeter that takes advantage of the low thermal diffusivity of water and the water-imperviousness of polyethylene film. An ultra-small bead thermistor is sandwiched between two thin polyethylene films stretched between insulative supports in a water bath. The polyethylene films insulate the thermistor and its leads, the leads being run out from between the films in insulated sleeving and then to junctions to form a wheatstone bridge circuit. Convection barriers may be provided to reduce the effects of convection from the point of measurement. Controlled heating of different levels in the water bath is accomplished by electrical heater circuits provided for controlling temperature drift and providing adiabatic operation of the calorimeter. The absorbed dose is determined from the known specific heat of water and the measured temperature change.

  10. 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.

  11. Evaluation of the minimum infectious dose of porcine epidemic diarrhea virus in virus-inoculated feed.

    PubMed

    Schumacher, Loni L; Woodworth, Jason C; Jones, Cassandra K; Chen, Qi; Zhang, Jianqiang; Gauger, Phillip C; Stark, Charles R; Main, Rodger G; Hesse, Richard A; Tokach, Mike D; Dritz, Steve S

    2016-10-01

    OBJECTIVE To determine the minimum infectious dose of porcine epidemic diarrhea virus (PEDV) in virus-inoculated feed. ANIMALS 30 crossbred 10-day-old pigs. PROCEDURES Tissue culture PEDV was diluted to form 8 serial 10-fold dilutions. An aliquot of stock virus (5.6 × 10(5) TCID50/mL) and each serial PEDV dilution were mixed into 4.5-kg batches of feed to create 9 PEDV-inoculated feed doses; 1 virus-negative dose of culture medium in feed was also created. Pigs were challenge exposed via oral administration of PEDV-inoculated feed, and fecal swab specimens were collected. All pigs were euthanized 7 days after challenge exposure; fresh tissues were collected and used for PCR assay, histologic examination, and immunohistochemical analysis. RESULTS The PCR cycle threshold (Ct) decreased by approximately 10 when PEDV was added to feed, compared with results for equivalent PEDV diluted in tissue culture medium. Pigs became infected with PEDV when challenge exposed with the 4 highest concentrations (lowest concentration to cause infection, 5.6 × 10(1) TCID50/g; Ct = 27 in tissue culture medium and 37 in feed). CONCLUSIONS AND CLINICAL RELEVANCE In this study, PEDV in feed with detectable Ct values of 27 to 37 was infective. The Ct was 37 for the lowest infective PEDV dose in feed, which may be above the limit of detection established for PEDV PCR assays used by some diagnostic laboratories. Overall, results indicated 5.6 × 10(1) TCID50/g was the minimum PEDV dose in feed that can lead to infection in 10-day-old pigs under the conditions of this study. PMID:27668582

  12. On higher structures

    NASA Astrophysics Data System (ADS)

    Baas, Nils A.

    2016-08-01

    In this paper, we discuss various philosophical aspects of the hyperstructure concept extending networks and higher categories. By this discussion, we hope to pave the way for applications and further developments of the mathematical theory of hyperstructures.

  13. Forecasting Higher Education's Future.

    ERIC Educational Resources Information Center

    Boyken, Don; Buck, Tina S.; Kollie, Ellen; Przyborowski, Danielle; Rondinelli, Joseph A.; Hunter, Jeff; Hanna, Jeff

    2003-01-01

    Offers predictions on trends in higher education to accommodate changing needs, lower budgets, and increased enrollment. They involve campus construction, security, administration, technology, interior design, athletics, and transportation. (EV)

  14. International Higher Education Bibliography.

    ERIC Educational Resources Information Center

    Lulat, Y. G-M.

    1988-01-01

    One in a series of bibliographies of articles in international higher education journals lists items on a variety of administrative, financial, faculty, student, curricular, and related issues. Articles on specific geographic regions are categorized separately. (MSE)

  15. Iodine-129 Dose in LLW Disposal Facility Performance Assessments

    SciTech Connect

    Wilhite, E.L.

    1999-10-15

    Iodine-129 has the lowest Performance Assessment derived inventory limit in SRS disposal facilities. Because iodine is concentrated in the body to one organ, the thyroid, it has been thought that dilution with stable iodine would reduce the dose effects of 129I.Examination of the dose model used to establish the Dose conversion factor for 129I shows that, at the levels considered in performance assessments of low-level waste disposal facilities, the calculated 129I dose already accounts for ingestion of stable iodine. At higher than normal iodine ingestion rates, the uptake of iodine by the thyroid itself decrease, which effectively cancels out the isotopic dilution effect.

  16. High-resolution low-dose scanning transmission electron microscopy

    PubMed Central

    Buban, James P.; Ramasse, Quentin; Gipson, Bryant; Browning, Nigel D.; Stahlberg, Henning

    2010-01-01

    During the past two decades instrumentation in scanning transmission electron microscopy (STEM) has pushed toward higher intensity electron probes to increase the signal-to-noise ratio of recorded images. While this is suitable for robust specimens, biological specimens require a much reduced electron dose for high-resolution imaging. We describe here protocols for low-dose STEM image recording with a conventional field-emission gun STEM, while maintaining the high-resolution capability of the instrument. Our findings show that a combination of reduced pixel dwell time and reduced gun current can achieve radiation doses comparable to low-dose TEM. PMID:19915208

  17. High-resolution low-dose scanning transmission electron microscopy.

    PubMed

    Buban, James P; Ramasse, Quentin; Gipson, Bryant; Browning, Nigel D; Stahlberg, Henning

    2010-01-01

    During the past two decades instrumentation in scanning transmission electron microscopy (STEM) has pushed toward higher intensity electron probes to increase the signal-to-noise ratio of recorded images. While this is suitable for robust specimens, biological specimens require a much reduced electron dose for high-resolution imaging. We describe here protocols for low-dose STEM image recording with a conventional field-emission gun STEM, while maintaining the high-resolution capability of the instrument. Our findings show that a combination of reduced pixel dwell time and reduced gun current can achieve radiation doses comparable to low-dose TEM.

  18. Impact of microscopic disease extension, extra-CTV tumour islets, incidental dose and dose conformity on tumour control probability.

    PubMed

    Selvaraj, Jothybasu; Baker, Colin; Nahum, Alan

    2016-06-01

    The impact of microscopic disease extension (MDE), extra-CTV tumour islets (TIs), incidental dose and dose conformity on tumour control probability (TCP) is analyzed using insilico simulations in this study. MDE in the region in between GTV and CTV is simulated inclusive of geometric uncertainties (GE) using spherical targets and spherical dose distribution. To study the effect of incidental dose on TIs and the effect of dose-response curve (DRC) on tumour control, islets were randomly distributed and TCP was calculated for various dose levels by rescaling the dose. Further, the impact of dose conformity on required PTV margins is also studied. The required PTV margins are ~2 mm lesser than assuming a uniform clonogen density if an exponential clonogen density fall off in the GTV-CTV is assumed. However, margins are almost equal if GE is higher in both cases. This shows that GE has a profound impact on margins. The effect of TIs showed a bi-phasic relation with increasing dose, indicating that patients with islets not in the beam paths do not benefit from dose escalation. Increasing dose conformity is also found to have considerable effect on TCP loss especially for larger GE. Further, smaller margins in IGRT should be used with caution where uncertainty in CTV definition is of concern. PMID:27168065

  19. Impact of microscopic disease extension, extra-CTV tumour islets, incidental dose and dose conformity on tumour control probability.

    PubMed

    Selvaraj, Jothybasu; Baker, Colin; Nahum, Alan

    2016-06-01

    The impact of microscopic disease extension (MDE), extra-CTV tumour islets (TIs), incidental dose and dose conformity on tumour control probability (TCP) is analyzed using insilico simulations in this study. MDE in the region in between GTV and CTV is simulated inclusive of geometric uncertainties (GE) using spherical targets and spherical dose distribution. To study the effect of incidental dose on TIs and the effect of dose-response curve (DRC) on tumour control, islets were randomly distributed and TCP was calculated for various dose levels by rescaling the dose. Further, the impact of dose conformity on required PTV margins is also studied. The required PTV margins are ~2 mm lesser than assuming a uniform clonogen density if an exponential clonogen density fall off in the GTV-CTV is assumed. However, margins are almost equal if GE is higher in both cases. This shows that GE has a profound impact on margins. The effect of TIs showed a bi-phasic relation with increasing dose, indicating that patients with islets not in the beam paths do not benefit from dose escalation. Increasing dose conformity is also found to have considerable effect on TCP loss especially for larger GE. Further, smaller margins in IGRT should be used with caution where uncertainty in CTV definition is of concern.

  20. Comparison of dose distributions around the pulsed-dose-rate Fletcher Williamson and the low-dose-rate Fletcher Suit Delclos ovoids: a Monte Carlo study

    NASA Astrophysics Data System (ADS)

    Price, Michael J.; Gifford, Kent A.; Horton, John; Lawyer, Ann; Eifel, Patricia; Mourtada, Firas

    2006-08-01

    We performed a Monte Carlo study to compare dose distributions for a Fletcher-Suit-Delclos (FSD) ovoid used with 137Cs low-dose-rate (LDR) sources with those for a Fletcher-Williamson (FW) ovoid used with an 192Ir pulsed-dose-rate (PDR) source for intracavitary brachytherapy of cervical cancer. We recently reported on extensive validation of Monte Carlo MCNPX models of these ovoids using radiochromic film measurements. Here, we compared these models assuming identical loading of 10, 15 and 20 mgRaEq (72, 108 and 145 cGy cm2 h-1, respectively) in three dose mesh planes: one perpendicular to the ovoid long axis bisecting the ovoid, one parallel to and displaced 2 cm medially from the long axis of the ovoid, and a 'rectal' plane perpendicular to the long axis located 1 cm distal to the distal face of the ovoid cap. The FW ovoid delivered slightly higher doses (within 10%) over all loadings to regions away from the bladder and rectal shields when compared to the FSD ovoid. However, the FW ovoid delivered much higher doses (>50%) in regions near these shields. In the rectal plane, the FW ovoid delivered a slightly higher dose, but within the region directly behind the rectal shield, the FW ovoid delivered a dose ranging from +35% to -35% of the FSD dose distribution. We attribute these differences to intrinsic differences in source characteristics (radial dose function and anisotropy factors) and extrinsic factors such as the solid-angle effect between sources and shields and applicator design.

  1. Out-of-field doses and neutron dose equivalents for electron beams from modern Varian and Elekta linear accelerators.

    PubMed

    Cardenas, Carlos E; Nitsch, Paige L; Kudchadker, Rajat J; Howell, Rebecca M; Kry, Stephen F

    2016-01-01

    Out-of-field doses from radiotherapy can cause harmful side effects or eventually lead to secondary cancers. Scattered doses outside the applicator field, neutron source strength values, and neutron dose equivalents have not been broadly investigated for high-energy electron beams. To better understand the extent of these exposures, we measured out-of-field dose characteristics of electron applicators for high-energy electron beams on two Varian 21iXs, a Varian TrueBeam, and an Elekta Versa HD operating at various energy levels. Out-of-field dose profiles and percent depth-dose curves were measured in a Wellhofer water phantom using a Farmer ion chamber. Neutron dose was assessed using a combination of moderator buckets and gold activation foils placed on the treatment couch at various locations in the patient plane on both the Varian 21iX and Elekta Versa HD linear accelerators. Our findings showed that out-of-field electron doses were highest for the highest electron energies. These doses typically decreased with increasing distance from the field edge but showed substantial increases over some distance ranges. The Elekta linear accelerator had higher electron out-of-field doses than the Varian units examined, and the Elekta dose profiles exhibited a second dose peak about 20 to 30 cm from central-axis, which was found to be higher than typical out-of-field doses from photon beams. Electron doses decreased sharply with depth before becoming nearly constant; the dose was found to decrease to a depth of approximately E(MeV)/4 in cm. With respect to neutron dosimetry, Q values and neutron dose equivalents increased with electron beam energy. Neutron contamination from electron beams was found to be much lower than that from photon beams. Even though the neutron dose equivalent for electron beams represented a small portion of neutron doses observed under photon beams, neutron doses from electron beams may need to be considered for special cases. PMID:27455499

  2. Genomic Instability Induced by Low Dose Irradiation

    SciTech Connect

    Evans, Helen H. Sedwick, David W. Veigl, Martina L.

    2006-07-15

    The goal of this project was to determine if genomic instability could be initiated by poorly repaired DNA damage induced by low doses of ionizing radiation leading to a mutator phenotype. Human cells were irradiated, then transfected with an unirradiated reporter gene at various times AFTER exposure. The vector carried an inactive GFP gene that fluoresced when the gene was activated by a delayed mutation. Fluorescent cells were measured in the interval of 50 hours to four days after transfection. The results showed that delayed mutations occurred in these cells after exposure to relatively low doses (0.3-1.0 Gy) of low or high ionizing radiation, as well as after treatment with hyrodgen peroxide (30-100 micromolar). The occurrence was both dose and time dependent, often decreasing at higher doses and later times. No marked difference was observed between the response of mis-match repair-proficient and -deficient cell lines. Although the results were quite reproducible within single experiments, difficulties were observed from experiment to experiment. Different reagents and assays were tested, but no improvement resulted. We concluded that this method is not sufficiently robust or consisent to be useful in the assay of the induction of genomic instability by low doses of radiation, at least in these cell lines under our conditions.

  3. Association of achieved dialysis dose with mortality in the hemodialysis study: an example of "dose-targeting bias".

    PubMed

    Greene, Tom; Daugirdas, John; Depner, Thomas; Allon, Michael; Beck, Gerald; Chumlea, Cameron; Delmez, James; Gotch, Frank; Kusek, John W; Levin, Nathan; Owen, William; Schulman, Gerald; Star, Robert; Toto, Robert; Eknoyan, Garabed

    2005-11-01

    In the intention-to-treat analysis of the Hemodialysis Study, all-cause mortality did not differ significantly between the high versus standard hemodialysis dose groups. The association of mortality with delivered dose within each of the two randomized treatment groups was examined, and implications for observational studies were considered. Time-dependent Cox regression was used to relate the relative risk (RR) for mortality to the running mean of the achieved equilibrated Kt/V (eKt/V) over the preceding 4 mo. eKt/V was categorized by quintiles within each dose group. Analyses were controlled for case-mix factors and baseline anthropometric volume. Within each randomized dose group, mortality was elevated markedly when achieved eKt/V was in the lowest quintile (RR, 1.93; 95% confidence interval [CI], 1.40 to 2.66; P < 0.0001 in the standard-dose group; RR, 2.04; 95% CI, 1.50 to 2.76; P < 0.0001 in the high-dose group; RR relative to the middle quintiles). The mortality rate in the lowest eKt/V quintile of the high-dose group was higher than in the full standard-dose group (RR, 1.59; 95% CI, 1.29 to 1.96; P < 0.0001). Each 0.1 eKt/V unit below the group median was associated with a 58% higher mortality in the standard-dose group (P < 0.001) and a 37% higher mortality in the high-dose group (P < 0.001). The magnitude of these dose-mortality effects was seven- to 12-fold higher than the upper limit of the 95% CI from the intention-to-treat analysis. The effects were attenuated in lagged analyses but did not disappear. When dialysis dose is targeted closely, as under the controlled conditions of the Hemodialysis Study, patients with the lowest achieved dose relative to their target dose experience markedly increased mortality, to a degree that is not compatible with a biologic effect of dose. The possibility of similar (albeit smaller) biases should be considered when analyzing observational data sets relating mortality to achieved dose of dialysis. PMID:16192421

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification

    PubMed Central

    Scheiber, Daniel; Veulemans, Verena; Horn, Patrick; Chatrou, Martijn L.; Potthoff, Sebastian A.; Kelm, Malte; Schurgers, Leon J.; Westenfeld, Ralf

    2015-01-01

    Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures. PMID:26295257

  9. High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification.

    PubMed

    Scheiber, Daniel; Veulemans, Verena; Horn, Patrick; Chatrou, Martijn L; Potthoff, Sebastian A; Kelm, Malte; Schurgers, Leon J; Westenfeld, Ralf

    2015-08-01

    Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures. PMID:26295257

  10. Biological-Based Modeling of Low Dose Radiation Risks

    SciTech Connect

    Scott, Bobby R., Ph.D.

    2006-11-08

    threshold. However, low-dose and low-dose-rate induced adapted protection leads to hormetic type dose-response relationships (e.g. U or J shaped) for cancer induction. Indeed, our research findings point to several dose zones of biological responses: (1) The natural background radiation dose zone over which increasing background radiation doses appear to lead to decrease cancer risk (Transition Zone A) due to activation (in a stochastic manner) of a system of protective processes that include high-fidelity DNA repair, apoptosis of unstable cells, and immune system activation. (2) A dose zone just above natural background radiation exposure over which cancer risk appears to further decrease and then remain suppressed at a relatively constant level below the spontaneous frequency (Zone of Maximal Protection); (3) higher but moderate doses over which cancer risk increases rather steeply over relative narrow dose range (Transition Zone B) due to radiation related suppression of protective processes (immune system function and selective apoptosis of unstable cells); (4) higher doses (LNT zone) where cancer risk increases as a linear function of dose for a range of doses (protective processes maximally suppressed in this zone). The indicted dose zones are dose-rate and radiation-type dependent with the protective zone increasing as dose rate is decreases and exposure time extended. In fact, natural background low-LET radiation appears to be protecting us not only from cancer occurrence but also from other genomic instability associated diseases via repeatedly inducing transient adapted protection. Reducing natural background radiation exposure (e.g., via relocation) over extended periods (years) would be expected to cause more harm than benefit. The harm would be expressed as increased cases of cancer and other genomic-instability-associated diseases as well as in significantly reduced life expectancy.

  11. Lactobacillus rhamnosus GG Activation of Dendritic Cells and Neutrophils Depends on the Dose and Time of Exposure.

    PubMed

    Cai, Shirong; Kandasamy, Matheswaran; Rahmat, Juwita N; Tham, Sin Mun; Bay, Boon Huat; Lee, Yuan Kun; Mahendran, Ratha

    2016-01-01

    This study evaluates the ability of Lactobacillus rhamnosus GG (LGG) to activate DC and neutrophils and modulate T cell activation and the impact of bacterial dose on these responses. Murine bone marrow derived DC or neutrophils were stimulated with LGG at ratios of 5 : 1, 10 : 1, and 100 : 1 (LGG : cells) and DC maturation (CD40, CD80, CD86, CD83, and MHC class II) and cytokine production (IL-10, TNF-α, and IL-12p70) were examined after 2 h and 18 h coculture and compared to the ability of BCG (the present immunotherapeutic agent for bladder cancer) to stimulate these cells. A 2 h exposure to 100 : 1 (high dose) or an 18 h exposure to 5 : 1 or 10 : 1 (low dose), LGG : cells, induced the highest production of IL-12 and upregulation of CD40, CD80, CD86, and MHC II on DC. In DCs stimulated with LGG activated neutrophils IL-12 production decreased with increasing dose. LGG induced 10-fold greater IL-12 production than BCG. T cell IFNγ and IL-2 production was significantly greater when stimulated with DC activated with low dose LGG. In conclusion, DC or DC activated with neutrophils exposed to low dose LGG induced greater Th1 polarization in T cells and this could potentially exert stronger antitumor effects. Thus the dose of LGG used for immunotherapy could determine treatment efficacy. PMID:27525288

  12. Lactobacillus rhamnosus GG Activation of Dendritic Cells and Neutrophils Depends on the Dose and Time of Exposure

    PubMed Central

    Bay, Boon Huat

    2016-01-01

    This study evaluates the ability of Lactobacillus rhamnosus GG (LGG) to activate DC and neutrophils and modulate T cell activation and the impact of bacterial dose on these responses. Murine bone marrow derived DC or neutrophils were stimulated with LGG at ratios of 5 : 1, 10 : 1, and 100 : 1 (LGG : cells) and DC maturation (CD40, CD80, CD86, CD83, and MHC class II) and cytokine production (IL-10, TNF-α, and IL-12p70) were examined after 2 h and 18 h coculture and compared to the ability of BCG (the present immunotherapeutic agent for bladder cancer) to stimulate these cells. A 2 h exposure to 100 : 1 (high dose) or an 18 h exposure to 5 : 1 or 10 : 1 (low dose), LGG : cells, induced the highest production of IL-12 and upregulation of CD40, CD80, CD86, and MHC II on DC. In DCs stimulated with LGG activated neutrophils IL-12 production decreased with increasing dose. LGG induced 10-fold greater IL-12 production than BCG. T cell IFNγ and IL-2 production was significantly greater when stimulated with DC activated with low dose LGG. In conclusion, DC or DC activated with neutrophils exposed to low dose LGG induced greater Th1 polarization in T cells and this could potentially exert stronger antitumor effects. Thus the dose of LGG used for immunotherapy could determine treatment efficacy. PMID:27525288

  13. Radiation dose to the lens and cataract formation

    SciTech Connect

    Henk, J.M.; Whitelocke, R.A.F.; Warrington, A.P.; Bessell, E.M. )

    1993-04-02

    The purpose of this work was to determine the radiation tolerance of the lens of the eye and the incidence of radiation-induced lens changes in patients treated by fractionated supervoltage radiation therapy for orbital tumors. Forty patients treated for orbital lymphoma and pseudotumor with tumor doses of 20--40 Gy were studied. The lens was partly shielded using lead cylinders in most cases. The dose to the germinative zone of the lens was estimated by measurements in a tissue equivalent phantom using both film densitometry and thermoluminescent dosimetry. Opthalmological examination was performed at 6 monthly intervals after treatment. The lead shield was found to reduce the dose to the germinative zone of the lens to between 36--50% of the tumor dose for Cobalt beam therapy, and to between 11--18% for 5 MeV x-rays. Consequently, the lens doses were in the range 4.5--30 Gy in 10--20 fractions. Lens opacities first appeared from between 3 and 9 years after irradiation. Impairment of visual acuity ensued in 74% of the patients who developed lens opacities. The incidence of lens changes was strongly dose-related. None was seen after doses of 5 Gy or lower, whereas doses of 16.5 Gy or higher were all followed by lens opacities which impaired visual acuity. The largest number of patients received a maximum lens dose of 15 Gy; in this group the actuarial incidence of lens opacities at 8 years was 57% with visual impairment in 38%. The adult lens can tolerate a total dose of 5 Gy during a fractionated course of supervoltage radiation therapy without showing any changes. Doses of 16.5 Gy or higher will almost invariably lead to visual impairment. The dose which causes a 50% probability of visual impairment is approximately 15 Gy. 10 refs., 4 figs., 1 tab.

  14. The Effects of ELDRS at Ultra-Low Dose Rates

    NASA Technical Reports Server (NTRS)

    Chen, Dakai; Forney, James; Carts, Martin; Phan, Anthony; Pease, Ronald; Kruckmeyer, Kirby; Cox, Stephen; LaBel, Kenneth; Burns, Samuel; Albarian, Rafi; Holcombe, Bruce; Little, Bradley; Salzman, James; Chaumont, Geraldine; Duperray, Herve; Ouellet, Al

    2011-01-01

    We present results on the effects on ELDRS at dose rates of 10, 5, 1, and 0.5 mrad(Si)/s for a variety of radiation hardened and commercial devices. We observed low dose rate enhancement below 10 mrad(Si)/s in several different parts. The magnitudes of the dose rate effects vary. The TL750L, a commercial voltage regulator, showed dose rate dependence in the functional failures, with initial failures occurring after 10 krad(Si) for the parts irradiated at 0.5 mrad(Si)/s. The RH1021 showed an increase in low dose rate enhancement by 2x at 5 mrad(Si)/s relative to 8 mrad(Si)/s and high dose rate, and parametric failure after 100 krad(Si). Additionally the ELDRS-free devices, such as the LM158 and LM117, showed evidence of dose rate sensitivity in parametric degradations. Several other parts also displayed dose rate enhancement, with relatively lower degradations up to approx.15 to 20 krad(Si). The magnitudes of the dose rate enhancement will likely increase in significance at higher total dose levels.

  15. Periodic CO2 Dosing Strategy for Dunaliella salina Batch Culture.

    PubMed

    Ying, Kezhen; Gilmour, D James; Zimmerman, William B

    2015-01-01

    A periodic CO2 dosing strategy for D. salina 19/30 batch culture is proposed. A model of periodic CO2 dosing including dosing time calculation, dosing interval estimation and final chlorophyll yield prediction was established. In experiments, 5% CO2/95% N2 gas was periodically dosed into D. salina culture. Two different gas dosing flow rates were tested. The corresponding dosing time for each flow rate was estimated via the model (10 min·d-1 for 0.7 L·min-1 and 36 min·d-1 for 0.3 L·min-1). Daily pH measurements showed that the pH of these cultures dosed periodically was always kept between 7.5 and 9.5, which highlights that periodic gas supply can maintain a suitable range of pH for microalgal growth without expensive buffers. Notably the culture dosed for set daily intervals was seen to have similar growth to the culture supplied constantly, but with much higher CO2 capture efficiency (11%-18%) compared to continuous dosing (0.25%). It shows great potential for using periodic gas supply to reduce cost, wasted gas and energy use.

  16. Radiobiological modelling of dose-gradient effects in low dose rate, high dose rate and pulsed brachytherapy

    NASA Astrophysics Data System (ADS)

    Armpilia, C.; Dale, R. G.; Sandilos, P.; Vlachos, L.

    2006-09-01

    This paper presents a generalization of a previously published methodology which quantified the radiobiological consequences of dose-gradient effects in brachytherapy applications. The methodology uses the linear-quadratic (LQ) formulation to identify an equivalent biologically effective dose (BEDeq) which, if applied uniformly to a specified tissue volume, would produce the same net cell survival as that achieved by a given non-uniform brachytherapy application. Multiplying factors (MFs), which enable the equivalent BED for an enclosed volume to be estimated from the BED calculated at the dose reference surface, have been calculated and tabulated for both spherical and cylindrical geometries. The main types of brachytherapy (high dose rate (HDR), low dose rate (LDR) and pulsed (PB)) have been examined for a range of radiobiological parameters/dimensions. Equivalent BEDs are consistently higher than the BEDs calculated at the reference surface by an amount which depends on the treatment prescription (magnitude of the prescribed dose) at the reference point. MFs are closely related to the numerical BED values, irrespective of how the original BED was attained (e.g., via HDR, LDR or PB). Thus, an average MF can be used for a given prescribed BED as it will be largely independent of the assumed radiobiological parameters (radiosensitivity and α/β) and standardized look-up tables may be applicable to all types of brachytherapy treatment. This analysis opens the way to more systematic approaches for correlating physical and biological effects in several types of brachytherapy and for the improved quantitative assessment and ranking of clinical treatments which involve a brachytherapy component.

  17. Comparative Higher Education.

    ERIC Educational Resources Information Center

    Altbach, Philip G.

    The comparative higher education course offered at the State University of New York at Buffalo is briefly described, and a course schedule is presented, including required and recommended readings for each topic. The course is intended to provide a broad cross-cultural perspective and considers the growth and development of universities in Europe,…

  18. Valuing Higher Education

    ERIC Educational Resources Information Center

    Pillay, Gerald J.

    2009-01-01

    The question of the value of higher education is today set in the context of an unprecedented banking and financial crisis. In this context of fundamental change and financial realignment, it is important that we as members of the university remake our case for why the university deserves to be considered alongside all those other worthy causes…

  19. Higher Education Exchange, 2003.

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    This annual collection focuses on the obligation of higher education to democracy. Scholars from a variety if disciplines explore this question and related issues, such as the civic mission of the university, what it means to be an "engaged" university, and how a university can itself by a "good citizen." Following a foreword by Deborah Witte, the…

  20. Higher Education's Strange Paradox.

    ERIC Educational Resources Information Center

    Howe, Harold, II

    The university which has had the temerity to change the world has not had the nerve to change itself to live in that world. The result is that the university's grading system, curriculum, teaching methods, and philosophies are in conflict with the world beyond the campus gates, and higher education does not meet the intellectual and social needs…

  1. European Higher Education Society

    ERIC Educational Resources Information Center

    Marcal-Grilo, Eduardo

    2003-01-01

    In his paper, the author--an academic and former Minister of Education for Portugal--traces the origins of the Bologna Declaration of 1999 and its follow-up studies leading to the Prague Conference of Higher Education Ministers in May 2001. He summarises the outcomes of the Prague Conference, and draws conclusions on the crucial role of…

  2. California's Future: Higher Education

    ERIC Educational Resources Information Center

    Johnson, Hans

    2015-01-01

    California's higher education system is not keeping up with the changing economy. Projections suggest that the state's economy will continue to need more highly educated workers. In 2025, if current trends persist, 41 percent of jobs will require at least a bachelor's degree and 36 percent will require some college education short of a bachelor's…

  3. Higher Education Interpreting.

    ERIC Educational Resources Information Center

    Woll, Bencie; Porcari li Destri, Giulia

    This paper discusses issues related to the training and provision of interpreters for deaf students at institutions of higher education in the United Kingdom. Background information provided notes the increasing numbers of deaf and partially hearing students, the existence of funding to pay for interpreters, and trends in the availability of…

  4. Understanding Higher Education Costs

    ERIC Educational Resources Information Center

    Middaugh, Michael F.

    2005-01-01

    Public discussion of higher education costs frequently confuses price with expenditure. This article examines factors associated with increases in the sticker price of a college education and the expenditures incurred by institutions in delivering that education. The discussion suggests that while growth in college tuition is real, access to…

  5. Urban Higher Education Consortia.

    ERIC Educational Resources Information Center

    Paltridge, James Gilbert

    This is a descriptive and evaluative study of 8 consortia formed by urban institutions of higher education confronted with common problems of minority student recruitment, training of teachers for inner-city schools, and the need for academic expertise to help solve their economic and social problems. Findings show that consortia weaknesses stem…

  6. Higher Level Thinking Abilities.

    ERIC Educational Resources Information Center

    Mills, Barbara, Ed.

    This report describes two systems designed to improve teaching competencies and to develop higher level thinking abilities, and presents the evaluation design, statistical results, and a brief history of the major events which occurred during development. The McCollum-Davis Model is designed to develop understanding of and skill in relating a…

  7. Workstations in Higher Education.

    ERIC Educational Resources Information Center

    Weissman, Ronald F. E.; And Others

    1988-01-01

    Five articles discuss various aspects of workstations and their applications in higher education. Highlights include microcomputers and workstations; UNIX operating system; campus-wide networks; software; Project SOCRATES and the interdisciplinary aspect of engineering; mechanical system design and simulation; and the Creation Station, a…

  8. Higher-order Multiples.

    PubMed

    Stone, Joanne; Kohari, Katherine S

    2015-09-01

    Higher-order multiple gestations have increased since the advent of advanced reproductive technologies. These pregnancies present unique risks to both mothers and fetuses. It is imperative that early diagnosis of chronicity be determined and that proper counseling is performed, so patients understand the risks, evaluation, and management needed.

  9. Higher Education in Scotland.

    ERIC Educational Resources Information Center

    Neave, Guy; Cowper, Henry

    1979-01-01

    Analyzes higher education in Scotland in terms of its history and administrative structure and in light of the myths and beliefs about the traditional Scottish university. Differences from English universities are stressed. Journal available from Editor, Gabriel Fragniere, Institute of Education, 60 rue de la Concorde, B-1050, Brussels, Belgium.…

  10. Black at Higher Education

    ERIC Educational Resources Information Center

    Kadi-Hanifi, Karima

    2013-01-01

    This is an exploratory paper, drawing on the author's experiences as well as those of three other black lecturers in Higher Education (HE). Three interviews were carried out, asking the same five questions around themes of concern to the author. These are about the learning and teaching approaches used by these lecturers; their experiences of…

  11. Women in Higher Education.

    ERIC Educational Resources Information Center

    Pifer, Alan

    Women have traditionally been discriminated against in higher education in both the attainment of degrees and in employment after earning degrees. It has been felt that women are not as capable, reliable, or effective as men in administrative and classroom situations. Statistics show that even at the present time women are underemployed and…

  12. Marketing in Higher Education.

    ERIC Educational Resources Information Center

    Hockenberger, Susan J.

    Educational institutions must seek new approaches to institutional planning because of such factors as shrinking traditional college age populations, eroding grants, governmental and judicial incursion, the tightening economic belt, and concern over the relevance of education to modern day needs. The concept of marketing higher education is…

  13. Higher Education Exchange.

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    This collection of 10 articles and stories highlights ongoing experiments in colleges and universities which address the relationship of higher education institutions and citizenship responsibility. Following a foreword by Deborah White, articles are: "The Civic Roots of Academic Social Science Scholarship in American" (R. Claire Snyder), which…

  14. Entrepreneurship and Higher Education

    ERIC Educational Resources Information Center

    Potter, Jonathan, Ed.

    2008-01-01

    Stimulating innovative and growth-oriented entrepreneurship is a key economic and societal challenge to which universities and colleges have much to contribute. This book examines the role that higher education institutions are currently playing through teaching entrepreneurship and transferring knowledge and innovation to enterprises and…

  15. Shell Higher Olefins Process.

    ERIC Educational Resources Information Center

    Lutz, E. F.

    1986-01-01

    Shows how olefin isomerization and the exotic olefin metathesis reaction can be harnessed in industrial processes. Indicates that the Shell Higher Olefins Process makes use of organometallic catalysts to manufacture alpha-olefins and internal carbon-11 through carbon-14 alkenes in a flexible fashion that can be adjusted to market needs. (JN)

  16. Unraveling Higher Education's Costs.

    ERIC Educational Resources Information Center

    Gordon, Gus; Charles, Maria

    1998-01-01

    The activity-based costing (ABC) method of analyzing institutional costs in higher education involves four procedures: determining the various discrete activities of the organization; calculating the cost of each; determining the cost drivers; tracing cost to the cost objective or consumer of each activity. Few American institutions have used the…

  17. Free Higher Education

    ERIC Educational Resources Information Center

    Reed, Jr., Adolph; Szymanski, Sharon

    2004-01-01

    The crisis of affordability in higher education is intensifying. Illustrations of its resonance abound: from the frequent news articles describing and amplifying the crisis and its sources to legislators' and candidates' proposed responses. Republicans' responses tend to be mainly punitive toward institutions; Democrats' proposals are more…

  18. Contracting and Higher Education.

    ERIC Educational Resources Information Center

    Ferris, James M.

    1991-01-01

    The potential gains in efficiency of three types of contracts in college administration are contrasted. Contract types include explicit contracts in the budgeting process between the state and higher education institutions; institutional contracting for inputs; and interinstitutional contracting. The tradeoff between production cost savings and…

  19. Women in Higher Education.

    ERIC Educational Resources Information Center

    O'Donnell, Sheryl, Ed.; Shaver, Barbara, Ed.

    1981-01-01

    Articles on women's studies and females in higher education are presented in this publication. A University of North Dakota project that sought to promote the integration of new research and scholarship results into the curriculum is described in "Women's Equity Committee Offers a Model Project," (Leola Furman, Robert Young). Historical…

  20. Developing Higher Level Thinking

    ERIC Educational Resources Information Center

    Limbach, Barbara; Waugh, Wendy

    2010-01-01

    This paper identifies an interdisciplinary, five-step process, built upon existing theory and best practices in cognitive development, effective learning environments, and outcomes-based assessment. The "Process for the Development of Higher Level Thinking Skills" provides teachers with an easy to implement method of moving toward a more…

  1. Leadership in Higher Education

    ERIC Educational Resources Information Center

    Amey, Marilyn J.

    2006-01-01

    At a time when seasoned higher-education leaders are retiring and the challenges facing prospective administrators seem daunting, how do those in positions of authority or aspiring to those roles construct a meaningful and manageable identity as leaders? Where do they look for support and inspiration? How do they learn to lead? The author…

  2. Liberty and Higher Education.

    ERIC Educational Resources Information Center

    Thompson, Dennis F.

    1989-01-01

    John Stuart Mill's principle of liberty is discussed with the view that it needs to be revised to guide moral judgments in higher education. Three key elements need to be modified: the action that is constrained; the constraint on the action; and the agent whose action is constrained. (MLW)

  3. Creativity in Higher Education

    ERIC Educational Resources Information Center

    Gaspar, Drazena; Mabic, Mirela

    2015-01-01

    The paper presents results of research related to perception of creativity in higher education made by the authors at the University of Mostar from Bosnia and Herzegovina. This research was based on a survey conducted among teachers and students at the University. The authors developed two types of questionnaires, one for teachers and the other…

  4. Marketing in Higher Education.

    ERIC Educational Resources Information Center

    Dalili, Farid

    The use of marketing activities by educational institutions and the transfer of marketing activities from business to higher education are considered. Market analysis helps colleges and universities determine what programs, scheduling, or services are strong and to which student market the institution should appeal. It is suggested that the…

  5. Curriculum in Higher Education.

    ERIC Educational Resources Information Center

    Rothman, A. I., Ed.

    1981-01-01

    Four articles on higher education curriculum are presented. In "The Articulate Curriculum" an approach to curriculum description is presented that is designed to have minimal ambiguity concerning the intention, content, and processes of the curriculum and that will lead to questioning several discrete factors in the curriculum planning process. It…

  6. Higher Education Exchange, 2013

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    2013-01-01

    The Kettering Foundation's research has been focused on putting the public back into the public's business for more than thirty years. Some questions that have recently been useful to Kettering researchers as the foundation focuses on its work with institutional actors--especially higher education and its relationship with the public--have…

  7. Online Higher Education Commodity

    ERIC Educational Resources Information Center

    Chau, Paule

    2010-01-01

    This article analyzes the current trend towards online education. It examines some of the reasons for the trend and the ramifications it may have on students, faculty and institutions of higher learning. The success and profitability of online programs and institutions such as the University of Phoenix has helped to make the move towards online…

  8. Higher spins and holography

    NASA Astrophysics Data System (ADS)

    Kraus, Per; Ross, Simon F.

    2013-05-01

    The principles of quantum mechanics and relativity impose rigid constraints on theories of massless particles with nonzero spin. Indeed, Yang-Mills theory and General Relativity are the unique solution in the case of spin-1 and spin-2. In asymptotically flat spacetime, there are fundamental obstacles to formulating fully consistent interacting theories of particles of spin greater than 2. However, indications are that such theories are just barely possible in asymptotically anti-de Sitter or de Sitter spacetimes, where the non-existence of an S-matrix provides an escape from the theorems restricting theories in Minkowski spacetime. These higher spin gravity theories are therefore of great intrinsic interest, since they, along with supergravity, provide the only known field theories generalizing the local invariance principles of Yang-Mills theory and General Relativity. While work on higher spin gravity goes back several decades, the subject has gained broader appeal in recent years due to its appearance in the AdS/CFT correspondence. In three and four spacetime dimensions, there exist duality proposals linking higher spin gravity theories to specific conformal field theories living in two and three dimensions respectively. The enlarged symmetry algebra of the conformal field theories renders them exactly soluble, which makes them excellent laboratories for understanding in detail the holographic mechanism behind AdS/CFT duality. Steady progress is also being made on better understanding the space of possible higher spin gravity theories and their physical content. This work includes classifying the possible field multiplets and their interactions, constructing exact solutions of the nonlinear field equations, and relating higher spin theories to string theory. A full understanding of these theories will involve coming to grips with the novel symmetry principles that enlarge those of General Relativity and Yang-Mills theory, and one can hope that this will provide

  9. Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

    SciTech Connect

    Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei

    2013-05-15

    Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor

  10. 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

  11. Radiation damage in single-particle cryo-electron microscopy: effects of dose and dose rate.

    PubMed

    Karuppasamy, Manikandan; Karimi Nejadasl, Fatemeh; Vulovic, Milos; Koster, Abraham J; Ravelli, Raimond B G

    2011-05-01

    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 combined with

  12. Guided medication dosing for elderly emergency patients using real-time, computerized decision support

    PubMed Central

    Lo, Helen G; Burdick, Elisabeth; Keohane, Carol; Bates, David W

    2011-01-01

    Objective To evaluate the impact of a real-time computerized decision support tool in the emergency department that guides medication dosing for the elderly on physician ordering behavior and on adverse drug events (ADEs). Design A prospective controlled trial was conducted over 26 weeks. The status of the decision support tool alternated OFF (7/17/06–8/29/06), ON (8/29/06–10/10/06), OFF (10/10/06–11/28/06), and ON (11/28/06–1/16/07) in consecutive blocks during the study period. In patients ≥65 who were ordered certain benzodiazepines, opiates, non-steroidals, or sedative-hypnotics, the computer application either adjusted the dosing or suggested a different medication. Physicians could accept or reject recommendations. Measurements The primary outcome compared medication ordering consistent with recommendations during ON versus OFF periods. Secondary outcomes included the admission rate, emergency department length of stay for discharged patients, 10-fold dosing orders, use of a second drug to reverse the original medication, and rate of ADEs using previously validated explicit chart review. Results 2398 orders were placed for 1407 patients over 1548 visits. The majority (49/53; 92.5%) of recommendations for alternate medications were declined. More orders were consistent with dosing recommendations during ON (403/1283; 31.4%) than OFF (256/1115; 23%) periods (p≤0.0001). 673 (43%) visits were reviewed for ADEs. The rate of ADEs was lower during ON (8/237; 3.4%) compared with OFF (31/436; 7.1%) periods (p=0.02). The remaining secondary outcomes showed no difference. Limitations Single institution study, retrospective chart review for ADEs. Conclusion Though overall agreement with recommendations was low, real-time computerized decision support resulted in greater acceptance of medication recommendations. Fewer ADEs were observed when computerized decision support was active. PMID:22052899

  13. [Fixed-dose combination].

    PubMed

    Nagai, Yoshio

    2015-03-01

    Many patients with type 2 diabetes mellitus(T2DM) do not achieve satisfactory glycemic control by monotherapy alone, and often require multiple oral hypoglycemic agents (OHAs). Combining OHAs with complementary mechanisms of action is fundamental to the management of T2DM. Fixed-dose combination therapy(FDC) offers a method of simplifying complex regimens. Efficacy and tolerability appear to be similar between FDC and treatment with individual agents. In addition, FDC can enhance adherence and improved adherence may result in improved glycemic control. Four FDC agents are available in Japan: pioglitazone-glimepiride, pioglitazone-metformin, pioglitazone-alogliptin, and voglibose-mitiglinide. In this review, the advantages and disadvantages of these four combinations are identified and discussed. PMID:25812374

  14. 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.

  15. Retrospective Reconstructions of Active Bone Marrow Dose-Volume Histograms

    SciTech Connect

    Veres, Cristina; Allodji, Rodrigue S.; Llanas, Damien; Vu Bezin, Jérémi; Chavaudra, Jean; Mège, Jean Pierre; Lefkopoulos, Dimitri; Quiniou, Eric; Deutsh, Eric; Vathaire, Florent de; Diallo, Ibrahima

    2014-12-01

    Purpose: To present a method for calculating dose-volume histograms (DVH's) to the active bone marrow (ABM) of patients who had undergone radiation therapy (RT) and subsequently developed leukemia. Methods and Materials: The study focuses on 15 patients treated between 1961 and 1996. Whole-body RT planning computed tomographic (CT) data were not available. We therefore generated representative whole-body CTs similar to patient anatomy. In addition, we developed a method enabling us to obtain information on the density distribution of ABM all over the skeleton. Dose could then be calculated in a series of points distributed all over the skeleton in such a way that their local density reflected age-specific data for ABM distribution. Dose to particular regions and dose-volume histograms of the entire ABM were estimated for all patients. Results: Depending on patient age, the total number of dose calculation points generated ranged from 1,190,970 to 4,108,524. The average dose to ABM ranged from 0.3 to 16.4 Gy. Dose-volume histograms analysis showed that the median doses (D{sub 50%}) ranged from 0.06 to 12.8 Gy. We also evaluated the inhomogeneity of individual patient ABM dose distribution according to clinical situation. It was evident that the coefficient of variation of the dose for the whole ABM ranged from 1.0 to 5.7, which means that the standard deviation could be more than 5 times higher than the mean. Conclusions: For patients with available long-term follow-up data, our method provides reconstruction of dose-volume data comparable to detailed dose calculations, which have become standard in modern CT-based 3-dimensional RT planning. Our strategy of using dose-volume histograms offers new perspectives to retrospective epidemiological studies.

  16. Dose of Prophylactic Platelet Transfusions and Prevention of Hemorrhage

    PubMed Central

    Slichter, Sherrill J.; Kaufman, Richard M.; Assmann, Susan F.; McCullough, Jeffrey; Triulzi, Darrell J.; Strauss, Ronald G.; Gernsheimer, Terry B.; Ness, Paul M.; Brecher, Mark E.; Josephson, Cassandra D.; Konkle, Barbara A.; Woodson, Robert D.; Ortel, Thomas L.; Hillyer, Christopher D.; Skerrett, Donna L.; McCrae, Keith R.; Sloan, Steven R.; Uhl, Lynne; George, James N.; Aquino, Victor M.; Manno, Catherine S.; McFarland, Janice G.; Hess, John R.; Leissinger, Cindy; Granger, Suzanne

    2010-01-01

    BACKGROUND We conducted a trial of prophylactic platelet transfusions to evaluate the effect of platelet dose on bleeding in patients with hypoproliferative thrombocytopenia. METHODS We randomly assigned hospitalized patients undergoing hematopoietic stem-cell transplantation or chemotherapy for hematologic cancers or solid tumors to receive prophylactic platelet transfusions at a low dose, a medium dose, or a high dose (1.1×1011, 2.2×1011, or 4.4×1011 platelets per square meter of body-surface area, respectively), when morning platelet counts were 10,000 per cubic millimeter or lower. Clinical signs of bleeding were assessed daily. The primary end point was bleeding of grade 2 or higher (as defined on the basis of World Health Organization criteria). RESULTS In the 1272 patients who received at least one platelet transfusion, the primary end point was observed in 71%, 69%, and 70% of the patients in the low-dose group, the medium-dose group, and the high-dose group, respectively (differences were not significant). The incidences of higher grades of bleeding, and other adverse events, were similar among the three groups. The median number of platelets transfused was significantly lower in the low-dose group (9.25×1011) than in the medium-dose group (11.25×1011) or the high-dose group (19.63×1011) (P = 0.002 for low vs. medium, P<0.001 for high vs. low and high vs. medium), but the median number of platelet transfusions given was significantly higher in the low-dose group (five, vs. three in the medium-dose and three in the high-dose group; P<0.001 for low vs. medium and low vs. high). Bleeding occurred on 25% of the study days on which morning platelet counts were 5000 per cubic millimeter or lower, as compared with 17% of study days on which platelet counts were 6000 to 80,000 per cubic millimeter (P<0.001). CONCLUSIONS Low doses of platelets administered as a prophylactic transfusion led to a decreased number of platelets transfused per patient but an

  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. 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.

  19. Adequacy of venlafaxine dose prescribing in major depression and hospital resources implications.

    PubMed

    Vanoli, A; Lane, C J; Harrison, Claire; Steen, N I; Young, A H

    2008-06-01

    Venlafaxine, a dual serotonin and noradrenaline re-uptake inhibitor, has been found to be effective at doses below 375 mg daily, but for patients with major depression higher doses can be required. In this retrospective naturalistic study, we investigated the effectiveness and resource implications of prescribing higher than standard doses of venlafaxine (tablet preparation). Ninety-six outpatients fulfilling DSM-IV criteria for major depressive disorder were assigned to two demographically matched cohorts: cohort A, receiving high doses (n = 38; doses > or =375 mg/day) and cohort B, receiving standard doses (n = 58; doses <375 mg/day). Data on hospital resources, drugs and medical profiles were extracted from patients' records. Information on cohort A was also obtained before their high-dose regime, while taking standard doses. A within-group analysis of cohort A showed that patients spent fewer days in hospital (P = 0.03) and had fewer outpatients visits (P < 0.01) when on high doses than when on standard doses. A between-group analysis found that cohort A, while on higher doses, had fewer outpatient visits compared with cohort B (P < 0.01). Patients in both groups had satisfactory drug tolerability and efficacy profiles. There were no differences between cohorts with regard to baseline characteristics, a part from the more intensive use of additional medications made by cohort A. Our preliminary investigation suggests that higher doses of venlafaxine may be cost-saving in relation to selected hospital resources. However, one cannot firmly conclude that the change in service use is due to the higher-dose regime, and we recommend further research to ascertain the cost-effectiveness of adequate dose prescribing in patients with poor symptom resolution at lower doses of venlafaxine.

  20. 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

  1. Time-Scheduled versus Pain-Contingent Opioid Dosing in Chronic Opioid Therapy

    PubMed Central

    Von Korff, Michael; Merrill, Joseph O.; Rutter, Carolyn M.; Sullivan, Mark; Campbell, Cynthia I.; Weisner, Constance

    2011-01-01

    Some expert guidelines recommend time-scheduled opioid dosing over pain-contingent dosing for patients receiving chronic opioid therapy (COT). The premise is that time-scheduled dosing results in more stable opioid blood levels and better pain relief, fewer side effects, less reinforcement of pain behaviors, and lower addiction risk. We report results of a survey of 1781 patients receiving COT for chronic non-cancer pain, in which 967 reported time-scheduled opioid dosing only and 325 reported pain-contingent opioid dosing only. Opioid-related problems and concerns were assessed with the Prescribed Opioids Difficulties Scale. We hypothesized that respondents using time-scheduled opioid dosing would report significantly fewer problems and concerns than those using pain-contingent dosing. Patients receiving time-scheduled dosing received substantially higher average daily opioid doses than those using pain-contingent dosing (97.2 vs. 37.2 milligrams average daily dose morphine equivalents, p<.0001). Contrary to expectation, time-scheduled opioid dosing was associated with higher levels of patient opioid control concerns than pain-contingent dosing (6.2 vs. 4.8, p=.008), after adjusting for patient and drug regimen differences. Opioid-related psychosocial problems were somewhat greater among patients using time-scheduled dosing, but this difference was non-significant after controlling for patient and drug regimen differences (5.9 versus 5.0, p=.14). Time-scheduled dosing typically involved higher dosage levels and was associated with higher levels of patient concerns about opioid use. Controlled comparative effectiveness research is needed to assess benefits and risks of time-scheduled opioid dosing relative to pain-contingent opioid dosing among COT patients in ambulatory care. PMID:21296498

  2. 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

  3. High-dose oral ziprasidone versus conventional dosing in schizophrenia patients with residual symptoms: the ZEBRAS study.

    PubMed

    Goff, Donald C; McEvoy, Joseph P; Citrome, Leslie; Mech, Arnold W; Bustillo, Juan R; Gil, Roberto; Buckley, Peter; Manschreck, Theo C; Achtyes, Eric D; Macklin, Eric A

    2013-08-01

    Uncontrolled studies have suggested that increasing the dose of ziprasidone above the standard maximum daily dose of 160 mg may be more effective for some patients with schizophrenia. To test this hypothesis, we conducted an 8-week, placebo-controlled, fixed-dose escalation trial comparing ziprasidone 160 versus 320 mg/d in individuals with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks. Of 75 randomized patients, 42 completed the study. Serum ziprasidone concentrations increased significantly in the high-dose group compared with the standard-dose group at week 4 but did not differ between groups at week 8. Both treatment groups exhibited significant symptomatic improvement. Response did not differ between treatment groups; however, in the high-dose group, higher ziprasidone serum concentrations were associated with better response at a trend level. Higher ziprasidone concentrations were also associated with reductions in diastolic blood pressure and, at a trend level, with more prominent negative symptoms and greater QTc prolongation. In summary, increasing the ziprasidone dose to 320 mg/d did not produce a sustained elevation in serum concentrations or symptomatic improvement compared with a standard ziprasidone dose of 160 mg/d.

  4. Higher order Bezier circles

    NASA Technical Reports Server (NTRS)

    Chou, Jin

    1993-01-01

    Rational Bezier and B-spline representations of circles have been heavily publicized. However, all the literature assumes the rational Bezier segments in the homogeneous space are both planar and (equivalent to) quadratic. This creates the illusion that circles can only be achieved by planar and quadratic curves. Circles that are formed by higher order rational Bezier curves which are nonplanar in the homogeneous space are shown. The problem of whether it is possible to represent a complete circle with one Bezier curve is investigated. In addition, some other interesting properties of cubic Bezier arcs are discussed.

  5. Impact of oral bisphenol A at reference doses on intestinal barrier function and sex differences after perinatal exposure in rats

    PubMed Central

    Braniste, Viorica; Jouault, Aurore; Gaultier, Eric; Polizzi, Arnaud; Buisson-Brenac, Claire; Leveque, Mathilde; Martin, Pascal G.; Theodorou, Vassilia; Fioramonti, Jean; Houdeau, Eric

    2009-01-01

    Bisphenol A (BPA), a chemical estrogen widely used in the food-packaging industry and baby bottles, is recovered in human fluids (0.1–10 nM). Recent studies have reported that BPA is hormonally active at low doses, emphasizing the debate of a risk for human health. Estrogen receptors are expressed in the colon, and although the major route of BPA exposure is food, the effects on gut have received no attention. We first examined the endocrine disrupting potency of BPA on colonic paracellular permeability (CPP), experimental colitis, and visceral sensitivity in ovariectomized rats orally exposed to 5 mg/kg/d BPA (i.e., the no observed adverse effect level), 50 μg/kg/d BPA (i.e., tolerable daily intake), or lower doses. BPA dose-dependently decreased basal CPP, with a half-maximal inhibitory dose of 5.2 μg/kg/d, 10-fold below the tolerable daily intake. This correlated with an increase in epithelial tight junction sealing, also observed in Caco-2 cells exposed to 10 nM BPA. When ovariectomized rats were fed with BPA at the no observed adverse effect level, the severity of colitis was reduced, whereas the same dose increased pain sensitivity to colorectal stimuli. We then examined the impact of perinatal exposure to BPA on intestinal permeability and inflammatory response in the offspring. In female rats, but not in male rats, perinatal BPA evoked a decrease of CPP in adulthood, whereas the proinflammatory response of colonic mucosa was strengthened. This study first demonstrates that the xenoestrogen BPA at reference doses influences intestinal barrier function and gut nociception. Moreover, perinatal exposure promotes the development of severe inflammation in adult female offspring only. PMID:20018722

  6. Dose and dose rate dependency of lipid peroxide formation in rat tissues by low level contamination with tritiated water

    NASA Astrophysics Data System (ADS)

    Moisoi, N.; Petcu, I.

    1999-01-01

    The changes in peroxide level in different tissues (liver, kidney, small intestine, spleen, bone marrow) of rats exposed to low levels of tritiated water were investigated in relation to tissue radiosensitivity, the irradiation dose and the dose rate domain. The radiation exposure was performed by internal contamination of rats with tritiated water, in the 0 50cGy dose domain, with dose rates in the range of 0.01 2cGy/day. For the lower dose rates (< 0.35cGy/day) the peroxide levels did not increase for doses up to 10cGy, while a dose rate of 1 1.75cGy/day induced an increase in peroxide levels starting at 5cGy. The increases were more significant for the tissues with higher radiosensitivity: spleen, small intestine and bone marrow. For the 4.2 7cGy dose domain and very low dose rates, up to 0.1cGy/day, the peroxide level seemed to have an inverse dose rate dependency. Nous avons étudié la modification du niveau des peroxydes lipidiques pour des tissus ayant des radiosensibilités différentes (foie, rein, rate, intestin grêle, moelle osseuse) après irradiation de rats par contamination interne à l'eau tritiée dans le domaine des faibles doses (0 - 50 cGy) et faibles débits de doses (0,01 - 2 cGy/jour). L'irradiation au débit de dose inférieure à 0,35 cGy/jour, n'augmente le niveau de peroxydation que pour des doses supérieures à 10 cGy. Par contre, le débit de 1-1.75 cGy/jour induit une augmentation significative du paramètre étudié à partir de la dose de 5 cGy. Cette augmentation est plus accentuée pour la rate, l'intestin grêle et la moelle osseuse. Aux doses de 4,2-7 cGy et débits de doses très faibles (< 0.1 cGy), le niveau de peroxydation montre une dépendance inverse par rapport au débit de dose.

  7. Higher than Everest

    NASA Astrophysics Data System (ADS)

    Hodge, Paul

    2001-08-01

    Tired of exploring planet Earth? Have you ever imagined what it would be like to explore the Moon? Ever wonder about the topography of Mars? In this unique guidebook all of your extraterrestrial wanderlust can be fulfilled as Paul Hodge takes you on a virtual tour of the most spectacular sites in the Solar System. Hodge includes the latest information about the Solar System into his vivid descriptions of imaginary, challenging expeditions. Imagine: -- Descending into a fabulous canyon on Mars, one that dwarfs the Earth's Grand Canyon; -- Trekking up Venus' precipitous and scorching Mt. Maxwell; -- Journeying through the snows of Saturn's rings and the incredibly high, icy cliff of Miranda, the moon closest to Uranus. A compelling, extensively illustrated introduction to such otherworldly environments, Higher than Everest makes you believe that someday these adventures may actually take place. Paul Hodge is Professor of Astronomy at the University of Washington, Seattle, and Editor-in-Chief of the Astronomical Journal. Higher than Everest is based on a popular undergraduate course on the planets that he has taught for many years. Hodge's research has spanned from interplanetary dust to the extragalactic distance scale and currently includes star-formation and galactic evolution, using the Hubble Space Telescope to investigate nearby galaxies. He has written several books, most recently Meteorite Craters and Impact Structures of the Earth (Cambridge 1994).

  8. Higher harmonic generation microscopy.

    PubMed

    Sun, Chi-Kuang

    2005-01-01

    Higher harmonic-generation, including second harmonic generation and third harmonic generation, leaves no energy deposition to the interacted matters due to its virtual-level transition characteristic, providing a truly non-invasive modality and is ideal for in vivo imaging of live specimens without any preparation. Second harmonic generation microscopy provides images on stacked membranes and arranged proteins with organized nano-structures due to the bio-photonic crystalline effect. Third harmonic generation microscopy provides general cellular or subcellular interface imaging due to optical inhomogeneity. Due to their virtual-transition nature, no saturation or bleaching in the generated signal is expected. With no energy release, continuous viewing without compromising sample viability can thus be achieved. Combined with its nonlinearity, higher harmonic generation microscopy provides sub-micron three-dimensional sectioning capability and millimeter penetration in live samples without using fluorescence and exogenous markers, offering morphological, structural, functional, and cellular information of biomedical specimens without modifying their natural biological and optical environments.

  9. Dose equivalent neutron dosimeter

    DOEpatents

    Griffith, Richard V.; Hankins, Dale E.; Tomasino, Luigi; Gomaa, Mohamed A. M.

    1983-01-01

    A neutron dosimeter is disclosed which provides a single measurements indicating the amount of potential biological damage resulting from the neutron exposure of the wearer, for a wide range of neutron energies. The dosimeter includes a detecting sheet of track etch detecting material such as a carbonate plastic, for detecting higher energy neutrons, and a radiator layer containing conversion material such as .sup.6 Li and .sup.10 B lying adjacent to the detecting sheet for converting moderate energy neutrons to alpha particles that produce tracks in the adjacent detecting sheet. The density of conversion material in the radiator layer is of an amount which is chosen so that the density of tracks produced in the detecting sheet is proportional to the biological damage done by neutrons, regardless of whether the tracks are produced as the result of moderate energy neutrons striking the radiator layer or as the result of higher energy neutrons striking the sheet of track etch material.

  10. 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.

  11. 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.

  12. 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.].

  13. Dose and dose rate effects of whole-body proton-irradiation on lymphocyte blastogenesis and hematological variables: part II

    NASA Technical Reports Server (NTRS)

    Pecaut, Michael J.; Gridley, Daila S.; Smith, Anna L.; Nelson, Gregory A.

    2002-01-01

    The goal of part II of this study was to evaluate functional characteristics of leukocytes and circulating blood cell parameters after whole-body proton irradiation at varying doses and at low- and high-dose-rates (LDR and HDR, respectively). C57BL/6 mice (n=51) were irradiated and euthanized at 4 days post-exposure for assay. Significant radiation dose- (but not dose-rate-) dependent decreases were observed in splenocyte responses to T and B cell mitogens when compared to sham-irradiated controls (P<0.001). Spontaneous blastogenesis, also significantly dose-dependent, was increased in both blood and spleen (P<0.001). Red blood cell counts, hemoglobin concentration, and hematocrit were decreased in a dose-dependent manner (P<0.05), whereas thrombocyte numbers were only slightly affected. Comparison of proton- and gamma-irradiated groups (both receiving 3 Gy at HDR) showed a higher level of spontaneous blastogenesis in blood leukocytes and a lower splenocyte response to concanavalin A following proton irradiation (P<0.05). There were no dose rate effects. Collectively, the data demonstrate that the measurements in blood and spleen were largely dependent upon the total dose of proton radiation and that an 80-fold difference in the dose rate was not a significant factor. A difference, however, was found between protons and gamma-rays in the degree of change induced in some of the measurements.

  14. 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

  15. Higher dimensional massive bigravity

    NASA Astrophysics Data System (ADS)

    Do, Tuan Q.

    2016-08-01

    We study higher-dimensional scenarios of massive bigravity, which is a very interesting extension of nonlinear massive gravity since its reference metric is assumed to be fully dynamical. In particular, the Einstein field equations along with the following constraint equations for both physical and reference metrics of a five-dimensional massive bigravity will be addressed. Then, we study some well-known cosmological spacetimes such as the Friedmann-Lemaitre-Robertson-Walker, Bianchi type I, and Schwarzschild-Tangherlini metrics for the five-dimensional massive bigravity. As a result, we find that massive graviton terms will serve as effective cosmological constants in both physical and reference sectors if a special scenario, in which reference metrics are chosen to be proportional to physical ones, is considered for all mentioned metrics. Thanks to the constancy property of massive graviton terms, consistent cosmological solutions will be figured out accordingly.

  16. Characteristics and Dose Levels for Spent Reactor Fuels

    SciTech Connect

    Coates, Cameron W

    2007-01-01

    Current guidance considers highly radioactive special nuclear materials to be those materials that, unshielded, emit a radiation dose [rate] measured at 1 m which exceeds 100 rem/h. Smaller, less massive fuel assemblies from research reactors can present a challenge from the point of view of self protection because of their size (lower dose, easier to handle) and the desirability of higher enrichments; however, a follow-on study to cross-compare dose trends of research reactors and power reactors was deemed useful to confirm/verify these trends. This paper summarizes the characteristics and dose levels of spent reactor fuels for both research reactors and power reactors and extends previous studies aimed at quantifying expected dose rates from research reactor fuels worldwide.

  17. Morphine at gramme doses: kinetics, dynamics and clinical need.

    PubMed

    Smith, K J; Miller, A J; McKellar, J; Court, M

    1991-01-01

    The MS Contin tablet 200 mg (controlled release morphine sulphate) provides an equivalent rate and extent of absorption to two MS Contin tablets 100 mg. The characteristics of controlled release from this higher strength formulation are also consistent with those of the 100 mg tablet. The level of analgesia provided during the early post-dosing period, at the end of the dosing period and overall over the twelve hour interval were also equivalent between the preparations. The addition of the MS Contin tablet 200 mg to the existing range will facilitate oral dosing in patients requiring large doses of morphine. This extension to the range will increase the choice available to the clinician and provide a natural progression for those patients requiring a step-up in the dose titration procedure.

  18. Radiation dose aspects in the handling of emerging nuclear fuels.

    PubMed

    Nicolaou, G

    2014-12-01

    The occupational annual dose levels, encountered at fabrication of emerging nuclear fuels, have been studied. Emerging fuels for the single and multiple recycling of Pu and MA have resulted in considerably higher gamma and neutron doses in comparison with commercial fuels. The occupational dose limit is exceeded at fabrication by a single fuel rod in all fuel cases with (241)Am and Cm isotopes present in their composition. In the absence of these isotopes, 2-4 adjacent fuel rods are sufficient to exceed the limit. Self-shielding within the fuel reduces significantly only the gamma dose that would have been delivered otherwise. Hence, only the first row of fuel rods in an assembly contributes to the dose, whereas in the case of neutrons, all fuel rods contribute.

  19. Culmination of Low-Dose Pesticide Effects

    PubMed Central

    2013-01-01

    Pesticides applied in agriculture can affect the structure and function of nontarget populations at lower doses and for longer timespans than predicted by the current risk assessment frameworks. We identified a mechanism for this observation. The populations of an aquatic invertebrate (Culex pipiens) exposed over several generations to repeated pulses of low concentrations of the neonicotinoid insecticide (thiacloprid) continuously declined and did not recover in the presence of a less sensitive competing species (Daphnia magna). By contrast, in the absence of a competitor, insecticide effects on the more sensitive species were only observed at concentrations 1 order of magnitude higher, and the species recovered more rapidly after a contamination event. The underlying processes are experimentally identified and reconstructed using a simulation model. We conclude that repeated toxicant pulse of populations that are challenged with interspecific competition may result in a multigenerational culmination of low-dose effects. PMID:23859631

  20. 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

  1. Low-dose ticagrelor yields an antiplatelet efficacy similar to that of standard-dose ticagrelor in healthy subjects: an open-label randomized controlled trial.

    PubMed

    Li, Pan; Gu, Ying; Yang, Yawei; Chen, Lizhi; Liu, Junmei; Gao, Lihong; Qin, Yongwen; Cai, Quancai; Zhao, Xianxian; Wang, Zhuo; Ma, Liping

    2016-01-01

    Ticagrelor has a greater antiplatelet efficacy than clopidogrel but may be accompanied by an increased risk of bleeding. This study evaluated the antiplatelet effect and pharmacokinetic profile of low-dose ticagrelor in healthy Chinese volunteers. Thirty healthy subjects were randomized to receive standard-dose ticagrelor (180-mg loading dose, 90-mg twice daily [bid] [n = 10]), low-dose ticagrelor (90-mg loading dose, 45-mg bid [n = 10]), or clopidogrel (600-mg loading dose, 75-mg once daily [n = 10]). Platelet reactivity was assessed by using the VerifyNow P2Y12 assay at baseline and 0.5, 1, 2, 4, 8, 24, 48, and 72 hours post-dosing. The ticagrelor and AR-C124910XX concentrations were measured for pharmacokinetic analysis. The percentage inhibition of P2Y12 reaction units was higher in the low-dose and standard-dose ticagrelor group than in the clopidogrel group at 0.5, 1, 2, 4, 8, and 48 hours post-dosing (P < 0.05 for all), but did not differ significantly between the two ticagrelor doses at any time-point (P > 0.05). The plasma ticagrelor and ARC124910XX concentrations were approximately 2-fold higher with standard-dose versus low-dose ticagrelor. No serious adverse events were reported. In conclusion, low-dose ticagrelor achieved faster and higher inhibition of platelet functions in healthy Chinese subjects than did clopidogrel, with an antiplatelet efficacy similar to that of standard-dose ticagrelor. PMID:27554803

  2. Low-dose ticagrelor yields an antiplatelet efficacy similar to that of standard-dose ticagrelor in healthy subjects: an open-label randomized controlled trial

    PubMed Central

    Li, Pan; Gu, Ying; Yang, Yawei; Chen, Lizhi; Liu, Junmei; Gao, Lihong; Qin, Yongwen; Cai, Quancai; Zhao, Xianxian; Wang, Zhuo; Ma, Liping

    2016-01-01

    Ticagrelor has a greater antiplatelet efficacy than clopidogrel but may be accompanied by an increased risk of bleeding. This study evaluated the antiplatelet effect and pharmacokinetic profile of low-dose ticagrelor in healthy Chinese volunteers. Thirty healthy subjects were randomized to receive standard-dose ticagrelor (180-mg loading dose, 90-mg twice daily [bid] [n = 10]), low-dose ticagrelor (90-mg loading dose, 45-mg bid [n = 10]), or clopidogrel (600-mg loading dose, 75-mg once daily [n = 10]). Platelet reactivity was assessed by using the VerifyNow P2Y12 assay at baseline and 0.5, 1, 2, 4, 8, 24, 48, and 72 hours post-dosing. The ticagrelor and AR-C124910XX concentrations were measured for pharmacokinetic analysis. The percentage inhibition of P2Y12 reaction units was higher in the low-dose and standard-dose ticagrelor group than in the clopidogrel group at 0.5, 1, 2, 4, 8, and 48 hours post-dosing (P < 0.05 for all), but did not differ significantly between the two ticagrelor doses at any time-point (P > 0.05). The plasma ticagrelor and ARC124910XX concentrations were approximately 2-fold higher with standard-dose versus low-dose ticagrelor. No serious adverse events were reported. In conclusion, low-dose ticagrelor achieved faster and higher inhibition of platelet functions in healthy Chinese subjects than did clopidogrel, with an antiplatelet efficacy similar to that of standard-dose ticagrelor. PMID:27554803

  3. Characterization of infectious dose and lethal dose of two strains of infectious hematopoietic necrosis virus (IHNV)

    USGS Publications Warehouse

    McKenney, Douglas; Kurath, Gael; Wargo, Andrew

    2016-01-01

    The ability to infect a host is a key trait of a virus, and differences in infectivity could put one virus at an evolutionary advantage over another. In this study we have quantified the infectivity of two strains of infectious hematopoietic necrosis virus (IHNV) that are known to differ in fitness and virulence. By exposing juvenile rainbow trout (Oncorhynchus mykiss) hosts to a wide range of virus doses, we were able to calculate the infectious dose in terms of ID50 values for the two genotypes. Lethal dose experiments were also conducted to confirm the virulence difference between the two virus genotypes, using a range of virus doses and holding fish either in isolation or in batch so as to calculate LD50values. We found that infectivity is positively correlated with virulence, with the more virulent genotype having higher infectivity. Additionally, infectivity increases more steeply over a short range of doses compared to virulence, which has a shallower increase. We also examined the data using models of virion interaction and found no evidence to suggest that virions have either an antagonistic or a synergistic effect on each other, supporting the independent action hypothesis in the process of IHNV infection of rainbow trout.

  4. 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.

  5. Higher prices in Jamaica.

    PubMed

    1982-03-01

    Price increases in the Jamaica CSM program went into effect on August 31, 1981. The program began in 1975. While the need for higher prices has been under discussion for the past 3 years, this is the 1st time the requisite approval from the Jamaica Price Commission has been obtained. The Jamaica National Family Planning Board (JNFPB) reports that the Panther 3-pack (condom) is up US$0.15 to US$0.30. Each Perle package (oral contraceptive) was increased by US$0.20. Single cycle Perle now sells for US$0.50, and 3-pack Perle sells for US$1.10. The 6-year price stagnation experienced by the CSM program resulted in a decreasing operational budget as program costs continued to rise. Marketing costs alone during this period escalated by 100-300%. For example, Panther pop-up display cartons cost the project US 16U each in 1975. By 1979 the same product cost US 49U. Newspaper advertisements have increased from the 1975 cost of US$68.00 to nearly $200.00 per placement. The overall inflation rate in Jamaica during the last 5 years has averaged more than 20% annually. In the face of these rising costs, outlet expansion for Perle has been prevented, wholesaler margins have been unavailable, and new retailer training has been discontinued. It is projected that the new prices will result in an annual increased revenues of US$80,000 which will be used to reinstate these essential marketing activities. The JNFPB is also planning to introduce a Panther 12-pack and Panther strips to the CSM product line. According to Marketing Manager Aston Evans, "We believe the public is now ready for this type of packaging" which is scheduled to be available soon. Panther is presently only available in a 3-pack, but annual sales have been steady. The new 12-pack will be stocked on supermarket shelves to provide higher product visibility and wider distribution. The selling price has been set as US$1.20 and is expected to yield a 25% increase in sales during the 1st year. A complete sales promotion

  6. 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.

  7. On determining dose rate constants spectroscopically

    SciTech Connect

    Rodriguez, M.; Rogers, D. W. O.

    2013-01-15

    Purpose: To investigate several aspects of the Chen and Nath spectroscopic method of determining the dose rate constants of {sup 125}I and {sup 103}Pd seeds [Z. Chen and R. Nath, Phys. Med. Biol. 55, 6089-6104 (2010)] including the accuracy of using a line or dual-point source approximation as done in their method, and the accuracy of ignoring the effects of the scattered photons in the spectra. Additionally, the authors investigate the accuracy of the literature's many different spectra for bare, i.e., unencapsulated {sup 125}I and {sup 103}Pd sources. Methods: Spectra generated by 14 {sup 125}I and 6 {sup 103}Pd seeds were calculated in vacuo at 10 cm from the source in a 2.7 Multiplication-Sign 2.7 Multiplication-Sign 0.05 cm{sup 3} voxel using the EGSnrc BrachyDose Monte Carlo code. Calculated spectra used the initial photon spectra recommended by AAPM's TG-43U1 and NCRP (National Council of Radiation Protection and Measurements) Report 58 for the {sup 125}I seeds, or TG-43U1 and NNDC(2000) (National Nuclear Data Center, 2000) for {sup 103}Pd seeds. The emitted spectra were treated as coming from a line or dual-point source in a Monte Carlo simulation to calculate the dose rate constant. The TG-43U1 definition of the dose rate constant was used. These calculations were performed using the full spectrum including scattered photons or using only the main peaks in the spectrum as done experimentally. Statistical uncertainties on the air kerma/history and the dose rate/history were Less-Than-Or-Slanted-Equal-To 0.2%. The dose rate constants were also calculated using Monte Carlo simulations of the full seed model. Results: The ratio of the intensity of the 31 keV line relative to that of the main peak in {sup 125}I spectra is, on average, 6.8% higher when calculated with the NCRP Report 58 initial spectrum vs that calculated with TG-43U1 initial spectrum. The {sup 103}Pd spectra exhibit an average 6.2% decrease in the 22.9 keV line relative to the main peak when

  8. Higher cancer risk continues after Chernobyl

    Cancer.gov

    Nearly 25 years after the accident at the Chernobyl nuclear power plant in Ukraine, exposure to radioactive iodine-131(I-131, a radioactive isotope) from fallout may be responsible for thyroid cancers that are still occurring among people who lived in the Chernobyl area and were children or adolescents at the time of the accident, researchers say. An international team of researchers led by the NCI found a clear dose-response relationship, in which higher absorption of radiation from I-131 led to an increased risk for thyroid cancer that has not seemed to diminish over time.

  9. Molecular Detection of Leptospira in Two Returned Travelers: Higher Bacterial Load in Cerebrospinal Fluid versus Serum or Plasma

    PubMed Central

    Waggoner, Jesse J.; Soda, Elizabeth A.; Seibert, Ryan; Grant, Philip; Pinsky, Benjamin A.

    2015-01-01

    Leptospirosis is a potentially severe illness in returned travelers. Patients often present with fever, headache, and neck pain, which may lead to a workup for meningitis including the acquisition of cerebrospinal fluid (CSF). Although Leptospira DNA has been detected in CSF by polymerase chain reaction (PCR), little data exist regarding the utility of testing CSF in addition to serum or plasma obtained on presentation. In this report, we present two cases of leptospirosis in returned travelers presenting with fever and headache. Our first patient had neutrophilic meningitis, and Leptospira was detectable only in CSF obtained on admission. The second patient had a normal CSF profile, but Leptospira was detected in CSF at a bacterial load 5- to 10-fold higher than that in plasma. CSF is an important specimen for the diagnosis of Leptospira by molecular methods and may yield an actionable diagnosis in the absence of leptospiremia. PMID:26033024

  10. 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.

  11. [Dialysis dose quantification in critically ill patients].

    PubMed

    Casino, Francesco Gaetano

    2010-01-01

    Acute kidney injury affects about 35% of intensive care unit patients. Renal replacement therapy is required in about 5% of such patients and is associated with a mortality rate as high as 50% to 80%. The latter is likely more related to the failure of extrarenal organs than to an insufficient dialysis dose. This could explain, at least in part, the findings of 2 recent trials (VA/ NIH and RENAL) where the expected dose-outcome relationship was not confirmed. These results cannot be taken to infer that assessing the dialysis dose is no longer required. The contrary is true, in that the common finding of large differences between prescribed and delivered doses calls for accurate dose assessment, at least to avoid underdialysis. The minimum adequate levels are now a Kt/V urea of 1.2 to 1.4 three times a week (3x/wk) on intermittent hemodialysis (IHD), and an effluent of 20 mL/kg/h for 85% of the time on continuous renal replacement therapy (CRTT). Both these parameters can be easily measured but are far from ideal indices because they account neither for residual renal function nor for irregular dose delivery. The equivalent renal urea clearance (EKRjc), by expressing the averaged renal+dialytic urea clearance over the whole treatment period, is able to account for the above factors. Although assessing EKRjc is quite complex, for regular 3x/wk IHD one could use the formula EKRjc=10 Kt/V+1 to compute that a Kt/V of 1.2 and 1.4 corresponds to an EKRjc of 13 and 15 mL/min, respectively. On the other hand, the hourly effluent per kg is numerically similar to EKRjc. On this basis it can be calculated that in non-prediluted really continuous treatment, the recommended CRRT dose (EKRjc=20 mL/min) is 33% higher than the EKRjc of 15 mL/min, corresponding to the recommended Kt/V of 1.4 on 3x/wk IHD.

  12. Evaluation of enzyme dose and dose-frequency in ameliorating substrate accumulation in MPS IIIA Huntaway dog brain.

    PubMed

    King, Barbara; Marshall, Neil; Beard, Helen; Hassiotis, Sofia; Trim, Paul J; Snel, Marten F; Rozaklis, Tina; Jolly, Robert D; Hopwood, John J; Hemsley, Kim M

    2015-03-01

    Intracerebrospinal fluid (CSF) infusion of replacement enzyme is under evaluation for amelioration of disease-related symptoms and biomarker changes in patients with the lysosomal storage disorder mucopolysaccharidosis type IIIA (MPS IIIA; www.clinicaltrials.gov ; NCT#01155778; #01299727). Determining the optimal dose/dose-frequency is important, given the invasive method for chronically supplying recombinant protein to the brain, the main site of symptom generation. To examine these variables, we utilised MPS IIIA Huntaway dogs, providing recombinant human sulphamidase (rhSGSH) to young pre-symptomatic dogs from an age when MPS IIIA dog brain exhibits significant accumulation of primary (heparan sulphate) and secondary (glycolipid) substrates. Enzyme was infused into CSF via the cisterna magna at one of two doses (3 mg or 15 mg/infusion), with the higher dose supplied at two different intervals; fortnightly or monthly. Euthanasia was carried out 24 h after the final injection. Dose- and frequency-dependent reductions in heparan sulphate were observed in CSF and deeper layers of cerebral cortex. When we examined the amount of immunostaining of the general endo/lysosomal marker, LIMP-2, or quantified activated microglia, the higher fortnightly dose resulted in superior outcomes in affected dogs. Secondary lesions such as accumulation of GM3 ganglioside and development of GAD-reactive axonal spheroids were treated to a similar degree by both rhSGSH doses and dose frequencies. Our findings indicate that the lower fortnightly dose is sub-optimal for ameliorating existing and preventing further development of disease-related pathology in young MPS IIIA dog brain; however, increasing the dose fivefold but halving the frequency of administration enabled near normalisation of disease-related biomarkers. PMID:25421091

  13. Radioactive Dose Assessment and NRC Verification of Licensee Dose Calculation.

    1994-09-16

    Version 00 PCDOSE was developed for the NRC to perform calculations to determine radioactive dose due to the annual averaged offsite release of liquid and gaseous effluent by U.S commercial nuclear power facilities. Using NRC approved dose assessment methodologies, it acts as an inspector's tool for verifying the compliance of the facility's dose assessment software. PCDOSE duplicates the calculations of the GASPAR II mainframe code as well as calculations using the methodologices of Reg. Guidemore » 1.109 Rev. 1 and NUREG-0133 by optional choice.« less

  14. A study on contralateral breast surface dose for various tangential field techniques and the impact of set-up error on this dose.

    PubMed

    Prabhakar, R; Haresh, K P; Julka, P K; Ganesh, T; Rath, G K; Joshi, R C; Sasindran, M; Naik, K K; Sridhar, P S

    2007-03-01

    The risk of inducing contralateral breast (CLB) cancer in patients undergoing tangential field irradiation for the treatment of breast cancer is a serious concern in radiation oncology. A bilateral breast phantom made of wax attached onto the Alderson Rando phantom was used for studying the CLB dose for techniques using physical wedges, EDWs, IMRT and open fields. The skin dose to the CLB was measured at four different points (3 cm from the medial border of the tangential field (P1), nipple (P3), axilla (P4), midpoint between P3 and P1 (P2)). The highest measured dose occurred at P1 with the 60 degrees physical wedges; it was 15.3% of the dose at isocentre. Similarly, the dose measured at P3 (nipple) with 60 degrees physical wedges was 1.90 times higher than the dose with 60 degrees EDWs. The dose at P1 for IMRT (7.8%) was almost the same as that for the open field (8.7%). The skin dose measured at the nipple was 2.1 - 10.9 % of the isocentre dose. The highest CLB doses were contributed by medial wedged fields. The dose to the CLB can be reduced by using IMRT or avoiding wedging the medial tangential fields. A set-up error in the longitudinal direction has little impact on the CLB dose. Set-up errors > 1 cm in the vertical and lateral directions have significant impact on the CLB dose. PMID:17508600

  15. Effective dose from direct and indirect digital panoramic units

    PubMed Central

    Lee, Gun-Sun; Kim, Jin-Soo; Seo, Yo-Seob

    2013-01-01

    Purpose This study aimed to provide comparative measurements of the effective dose from direct and indirect digital panoramic units according to phantoms and exposure parameters. Materials and Methods Dose measurements were carried out using a head phantom representing an average man (175 cm tall, 73.5 kg male) and a limbless whole body phantom representing an average woman (155 cm tall, 50 kg female). Lithium fluoride thermoluminescent dosimeter (TLD) chips were used for the dosimeter. Two direct and 2 indirect digital panoramic units were evaluated in this study. Effective doses were derived using 2007 International Commission on Radiological Protection (ICRP) recommendations. Results The effective doses of the 4 digital panoramic units ranged between 8.9 µSv and 37.8 µSv. By using the head phantom, the effective doses from the direct digital panoramic units (37.8 µSv, 27.6 µSv) were higher than those from the indirect units (8.9 µSv, 15.9 µSv). The same panoramic unit showed the difference in effective doses according to the gender of the phantom, numbers and locations of TLDs, and kVp. Conclusion To reasonably assess the radiation risk from various dental radiographic units, the effective doses should be obtained with the same numbers and locations of TLDs, and with standard hospital exposure. After that, it is necessary to survey the effective doses from various dental radiographic units according to the gender with the corresponding phantom. PMID:23807930

  16. Temporal compartmental dosing effects for robotic prostate stereotactic body radiotherapy

    NASA Astrophysics Data System (ADS)

    Shiao, Stephen L.; Sahgal, Arjun; Hu, Weigang; Jabbari, Siavash; Chuang, Cynthia; Descovich, Martina; Hsu, I.-Chow; Gottschalk, Alexander R.; Roach, Mack, III; Ma, Lijun

    2011-12-01

    The rate of dose accumulation within a given area of a target volume tends to vary significantly for non-isocentric delivery systems such as Cyberknife stereotactic body radiotherapy. In this study, we investigated whether intra-target temporal dose distributions produce significant variations in the biological equivalent dose. For the study, time courses of ten patients were reconstructed and calculation of a biologically equivalent uniform dose (EUD) was performed using a formula derived from the linear quadratic model (α/β = 3 for prostate cancer cells). The calculated EUD values obtained for the actual patient treatments were then compared with theoretical EUD values for delivering the same physical dose distribution except that the whole target being irradiated continuously (e.g. large-field ‘dose-bathing’ type of delivery). For all the case, the EUDs for the actual treatment delivery were found to correlate strongly with the EUDs for the large-field delivery: a linear correlation coefficient of R2 = 0.98 was obtained and the average EUD for the actual Cyberknife delivery was somewhat higher (5.0 ± 4.7%) than that for the large-field delivery. However, no statistical significance was detected between the two types of delivery (p = 0.21). We concluded that non-isocentric small-field Cyberknife delivery produced consistent biological dosing that tracked well with the constant-dose-rate, large-field-type delivery for prostate stereotactic body radiotherapy.

  17. Peripheral Doses from Noncoplanar IMRT for Pediatric Radiation Therapy

    SciTech Connect

    Kan, Monica W.K.; Leung, Lucullus H.T.; Kwong, Dora L.W.; Wong, Wicger; Lam, Nelson

    2010-01-01

    The use of noncoplanar intensity-modulated radiation therapy (IMRT) might result in better sparing of some critical organs because of a higher degree of freedom in beam angle optimization. However, this can lead to a potential increase in peripheral dose compared with coplanar IMRT. The peripheral dose from noncoplanar IMRT has not been previously quantified. This study examines the peripheral dose from noncoplanar IMRT compared with coplanar IMRT for pediatric radiation therapy. Five cases with different pediatric malignancies in head and neck were planned with both coplanar and noncoplanar IMRT techniques. The plans were performed such that the tumor coverage, conformality, and dose uniformity were comparable for both techniques. To measure the peripheral doses of the 2 techniques, thermoluminescent dosimeters (TLD) were placed in 10 different organs of a 5-year-old pediatric anthropomorphic phantom. With the use of noncoplanar beams, the peripheral doses to the spinal cord, bone marrow, lung, and breast were found to be 1.8-2.5 times of those using the coplanar technique. This is mainly because of the additional internal scatter dose from the noncoplanar beams. Although the use of noncoplanar technique can result in better sparing of certain organs such as the optic nerves, lens, or inner ears depending on how the beam angles were optimized on each patient, oncologists should be alert of the possibility of significantly increasing the peripheral doses to certain radiation-sensitive organs such as bone marrow and breast. This might increase the secondary cancer risk to patients at young age.

  18. Are there dangers in biologic dose reduction strategies?

    PubMed

    Chan, Christopher K Y; Holroyd, Christopher R; Mason, Alice; Zarroug, Jalaa; Edwards, Christopher J

    2016-07-01

    Biologic dose reduction strategies, for patients with inflammatory rheumatic diseases, have been assessed in multiple studies to assess outcomes compared to ongoing maintenance dosing. Whilst cessation in established disease usually leads to disease flare, dose tapering approaches for those achieving low disease activity often appear to be successful in the short term. However, tapering can be associated with a higher risk of losing disease control and rates of recapture of disease control using the original biologic dose vary between studies. Over relatively short periods of follow-up, a number of studies have shown no statistical difference in radiographic progression in patients tapering or discontinuing biologics. However, a Cochrane review found that radiographic and functional outcomes may be worse after TNF inhibitor discontinuation, and over long-term disease follow-up flares have been associated with radiographic progression and worse patient reported outcomes. To date, no studies of biological therapy dose reduction have specifically investigated the risk of increased immunogenicity or the effects on cardiovascular risk and other co-morbidities, although these remain important potential risks. In addition, whether there are greater dangers in certain dose reduction approaches such as a reduction in dose at the same frequency or a spacing of doses is not established.

  19. Texas Higher Education in Transition.

    ERIC Educational Resources Information Center

    Texas Coll. and Univ. System, Austin. Coordinating Board.

    The status of higher education in Texas is examined in this major report of changes in higher education over the past decade. Information on enrollment, cost, financial aid, job opportunities, and facilities in higher education institutions is given for private higher education, professional higher education, community colleges, and state colleges…

  20. Do pregnant women have a higher risk for venous thromboembolism following air travel?

    PubMed Central

    Izadi, Morteza; Alemzadeh-Ansari, Mohammad Javad; Kazemisaleh, Davood; Moshkani-Farahani, Maryam; Shafiee, Akbar

    2015-01-01

    International travel has become increasingly common and accessible, and it is part of everyday life in pregnant women. Venous thromboembolism (VTE) is a serious public health disorder that occurs following long-haul travel, especially after air travel. The normal pregnancy is accompanied by a state of hypercoagulability and hypofibrinolysis. Thus, it seems that pregnant women are at a higher risk of VTE following air travel, and, if they have preexisting risk factors, this risk would increase. There is limited data about travel-related VTE in pregnant women; therefore, in the present study, we tried to evaluate the pathogenesis of thrombosis, association of thrombosis and air travel, risk factors and prevention of VTE in pregnant women based on available evidences. Pregnancy is associated with a five- to 10-fold increased risk of VTE compared with nonpregnant women; however, during the postpartum period, this risk would increase to 20–80-fold. Furthermore, the risk of thrombosis is higher in individuals with preexisting risk factors, and the most common risk factor for VTE during pregnancy is a previous history of VTE. Pregnant women are at a higher risk for thrombosis compared with other women. Thus, the prevention of VTE and additional risk factors should be considered for all pregnant women who travel by plane. PMID:25802829

  1. Quetiapine: dose-response relationship in schizophrenia.

    PubMed

    Sparshatt, Anna; Jones, Sarah; Taylor, David

    2008-01-01

    Quetiapine is a widely used second-generation antipsychotic that is effective in the treatment of schizophrenia and bipolar mania. In recent years, various publications have suggested the possibility that, in some patients, higher than licensed dosages are necessary for full therapeutic effect. A 'high-dose' theory of quetiapine activity has developed, leading many prescribers to disregard the formal upper limit of the quetiapine dosage range (750 or 800 mg/day, depending on local labelling). In this review, we examine the clinical and neuroimaging data relating to the use of quetiapine in acute exacerbations of schizophrenia. Fixed-dose efficacy studies of immediate-release (IR) quetiapine suggest dosages of quetiapine of 150-450 mg/day are more effective than placebo and no less effective than dosages of 600 or 750 mg/day. A fixed-dose study of extended-release quetiapine indicated that dosages of 600 and 800 mg/day were equally efficacious and numerically superior to 400 mg/day. Dosages of IR quetiapine averaging between 254 and 525 mg/day have been shown to be equivalent in efficacy to standard dosages of conventional and other atypical antipsychotics. Pooled data support these findings. Effectiveness studies using quetiapine in daily doses averaging between 565 and 653 mg revealed quetiapine to be somewhat less effective than some comparator drugs. Support for the use of high-dosage quetiapine (>800 mg/day) is very limited: case reports, albeit numerous, describe quetiapine as showing therapeutic effects only at dosages above the licensed range; some data suggest widespread use of higher dosages in practice; and neuroimaging data suggest inadequate dopamine receptor occupancy at standard dosages (although these findings may reflect the low affinity of quetiapine for dopamine receptors). Overall, robust controlled data strongly suggest that the standard dosage range for quetiapine is appropriate for clinical use. The balance of evidence does not support the

  2. 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.

  3. Critical target and dose and dose-rate responses for the induction of chromosomal instability by ionizing radiation

    NASA Technical Reports Server (NTRS)

    Limoli, C. L.; Corcoran, J. J.; Milligan, J. R.; Ward, J. F.; Morgan, W. F.

    1999-01-01

    To investigate the critical target, dose response and dose-rate response for the induction of chromosomal instability by ionizing radiation, bromodeoxyuridine (BrdU)-substituted and unsubstituted GM10115 cells were exposed to a range of doses (0.1-10 Gy) and different dose rates (0.092-17.45 Gy min(-1)). The status of chromosomal stability was determined by fluorescence in situ hybridization approximately 20 generations after irradiation in clonal populations derived from single progenitor cells surviving acute exposure. Overall, nearly 700 individual clones representing over 140,000 metaphases were analyzed. In cells unsubstituted with BrdU, a dose response was found, where the probability of observing delayed chromosomal instability in any given clone was 3% per gray of X rays. For cells substituted with 25-66% BrdU, however, a dose response was observed only at low doses (<1.0 Gy); at higher doses (>1.0 Gy), the incidence of chromosomal instability leveled off. There was an increase in the frequency and complexity of chromosomal instability per unit dose compared to cells unsubstituted with BrdU. The frequency of chromosomal instability appeared to saturate around approximately 30%, an effect which occurred at much lower doses in the presence of BrdU. Changing the gamma-ray dose rate by a factor of 190 (0.092 to 17.45 Gy min(-1)) produced no significant differences in the frequency of chromosomal instability. The enhancement of chromosomal instability promoted by the presence of the BrdU argues that DNA comprises at least one of the critical targets important for the induction of this end point of genomic instability.

  4. The effect of dose, dose rate, route of administration, and species on tissue and blood levels of benzene metabolites.

    PubMed Central

    Henderson, R F; Sabourin, P J; Bechtold, W E; Griffith, W C; Medinsky, M A; Birnbaum, L S; Lucier, G W

    1989-01-01

    Studies were completed in F344/N rats and B6C3F1 mice to determine the effect of dose, dose rate, route of administration, and rodent species on formation of total and individual benzene metabolites. Oral doses of 50 mg/kg or higher saturated the capacity for benzene metabolism in both rats and mice, resulting in an increased proportion of the administered dose being exhaled as benzene. The saturating air concentration for benzene metabolism during 6-hr exposures was between 130 and 900 ppm. At the highest exposure concentration, rats exhaled approximately half of the internal dose retained at the end of the 6-hr exposure as benzene; mice exhaled only 15% as benzene. Mice were able to convert more of the inhaled benzene to metabolites than were rats. In addition, mice metabolized more of the benzene by pathways leading to the putative toxic metabolites, benzoquinone and muconaldehyde, than did rats. In both rats and mice, the effect of increasing dose, administered orally or by inhalation, was to increase the proportion of the total metabolites that were the products of detoxification pathways relative to the products of pathways leading to putative toxic metabolites. This indicates low-affinity, high-capacity pathways for detoxification and high-affinity, low-capacity pathways leading to putative toxic metabolites. If the results of rodent studies performed at high doses were used to assess the health risk at low-dose exposures to benzene, the toxicity of benzene would be underestimated. PMID:2792053

  5. Management of pediatric radiation dose using GE fluoroscopic equipment.

    PubMed

    Belanger, Barry; Boudry, John

    2006-09-01

    estimate of its dose reduction potential. Finally, two recently developed imaging techniques and their potential effect on dose utilization are discussed. Specifically, we discuss the dose benefits of rotational angiography and low frame rate imaging with advanced image processing in lieu of higher-dose digital subtraction. PMID:16862403

  6. Dose reduction in molecular breast imaging

    NASA Astrophysics Data System (ADS)

    Wagenaar, Douglas J.; Chowdhury, Samir; Hugg, James W.; Moats, Rex A.; Patt, Bradley E.

    2011-10-01

    Molecular Breast Imaging (MBI) is the imaging of radiolabeled drugs, cells, or nanoparticles for breast cancer detection, diagnosis, and treatment. Screening of broad populations of women for breast cancer with mammography has been augmented by the emergence of breast MRI in screening of women at high risk for breast cancer. Screening MBI may benefit the sub-population of women with dense breast tissue that obscures small tumors in mammography. Dedicated breast imaging equipment is necessary to enable detection of early-stage tumors less than 1 cm in size. Recent progress in the development of these instruments is reviewed. Pixellated CZT for single photon MBI imaging of 99mTc-sestamibi gives high detection sensitivity for early-stage tumors. The use of registered collimators in a near-field geometry gives significantly higher detection efficiency - a factor of 3.6-, which translates into an equivalent dose reduction factor given the same acquisition time. The radiation dose in the current MBI procedure has been reduced to the level of a four-view digital mammography study. In addition to screening of selected sub-populations, reduced MBI dose allows for dual-isotope, treatment planning, and repeated therapy assessment studies in the era of molecular medicine guided by quantitative molecular imaging.

  7. Multigroup neutron dose calculations for proton therapy

    SciTech Connect

    Kelsey Iv, Charles T; Prinja, Anil K

    2009-01-01

    We have developed tools for the preparation of coupled multigroup proton/neutron cross section libraries. Our method is to use NJOY to process evaluated nuclear data files for incident particles below 150 MeV and MCNPX to produce data for higher energies. We modified the XSEX3 program of the MCNPX code system to produce Legendre expansions of scattering matrices generated by sampling the physics models that are comparable to the output of the GROUPR routine of NJOY. Our code combines the low and high energy scattering data with user input stopping powers and energy deposition cross sections that we also calculated using MCNPX. Our code also calculates momentum transfer coefficients for the library and optionally applies an energy straggling model to the scattering cross sections and stopping powers. The motivation was initially for deterministic solution of space radiation shielding calculations using Attila, but noting that proton therapy treatment planning may neglect secondary neutron dose assessments because of difficulty and expense, we have also investigated the feasibility of multi group methods for this application. We have shown that multigroup MCNPX solutions for secondary neutron dose compare well with continuous energy solutions and are obtainable with less than half computational cost. This efficiency comparison neglects the cost of preparing the library data, but this becomes negligible when distributed over many multi group calculations. Our deterministic calculations illustrate recognized obstacles that may have to be overcome before discrete ordinates methods can be efficient alternatives for proton therapy neutron dose calculations.

  8. Discussion on the usefulness of dose dynamic multi-leaf collimator-based plan to overcome dose limit of spinal cord in high-dose radiotherapy

    NASA Astrophysics Data System (ADS)

    Kim, E. C.; Cho, J. H.; Park, C. S.; Kim, D. H.; Choi, C. W.

    2014-03-01

    In this study, the conventional plan was compared with the plan that was based on a dose dynamic multi-leaf collimator (MLC), and a dose dynamic MLC was used to evaluate its usefulness. Then, this study examined if it was possible to perform a high-dose radiation therapy by adjusting the dose limit of the spinal cord when the dose dynamic MLC-based plan was used. First of all, linear accelerator was used to compare the conventional plan with the dose dynamic MLC-based plan. Then, the study was conducted in two methods in order to examine the proper range of the shield for the spinal cord when the dose dynamic MLC was used to adjust the dose of the spinal cord. In the first method, X-omat film was used to perform film dosimetry. In the second method, radiation treatment planning (RTP) system was used to find out the proper range among 0, 3, 6, and 9 mm. When film scan was performed in the each range, respectively, from the spinal cord and under the same conditions, it was confirmed to be appropriate to use the range of 3 mm. When the RTP system was used to perform planning in the shield range of each range, respectively, from the spinal cord, dose-volume histogram (DVH) was a slight difference could be found in the region from 25% to 35%. On the contrary, no radiation exposure was found in the region of 35% or higher for all of the each range. Consequently, if MLC is selected in consideration of the planning target volume (PTV), the most proper value can be obtained by selecting the range of 3 mm. Next, the DVH was compared to examine the relationship in PTV when the each range was used for planning. All of the ranges showed the same pattern up to the point of 90%. However, the results were different in the region of higher than 90% because the dose was low for the spinal cord, and a relatively useful dose was used for PTV when the range was 3 mm.

  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 being managed and conducted by the Pacific Northwest Laboratory (PNL) under the direction of an independent Technical Steering Panel (TSP). 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 and Washington, 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 human (dose estimates): Source Terms; Environmental Transport; Environmental Monitoring Data; Demographics, Agriculture, Food Habits and; Environmental Pathways and Dose Estimates.

  10. 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.

  11. Estimate Radiological Dose for Animals

    1997-12-18

    Estimate Radiological dose for animals in ecological environment using open literature values for parameters such as body weight, plant and soil ingestion rate, rad. halflife, absorbed energy, biological halflife, gamma energy per decay, soil-to-plant transfer factor, ...etc

  12. Individual and collective doses from cosmic radiation in Ireland.

    PubMed

    Colgan, P A; Synnott, H; Fenton, D

    2007-01-01

    This paper assesses the individual and collective doses in Ireland due to cosmic radiation. Information on the exposure to cosmic radiation at ground level is reviewed and published data on the frequency of routes flown by Irish residents is used to calculate the dose due to air travel. Occupational exposure of aircrew is also evaluated. Experimental data on cosmic radiation exposure at ground level is in good agreement with international estimates and the average individual dose is calculated as 300 microSv annually. Published data on international air travel by Irish residents shows a 50% increase in the number of flights taken between 2001 and 2005. This increase is primarily on short-haul flights to Europe, but there have been significant percentage increases in all long-haul flights, with the exception of flights to Africa. The additional per capita dose due to air travel is estimated to be 45 muSv, of which 51% is accumulated on European routes and 34% on routes to the United States. Exposure of aircrew to cosmic radiation is now controlled by legislation and all airlines holding an Air Operator's Certificate issued by the Irish Aviation Authority are required to report annually the doses received by their employees in the previous year. There has been a 75% increase in the number of aircrew receiving doses >1 mSv since 2002. In 2004 and 2005 the average individual doses received by Irish aircrew were 1.8 and 2.0, mSv, respectively. The corresponding per caput dose for the entire population is <3 muSv. While this is low compared with the per caput doses from other sources of cosmic radiation, aircrew exposure represents a higher collective dose than any other identified group of exposed workers in Ireland.

  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. Methemoglobin-Based Biological Dose Assessment for Human Blood.

    PubMed

    Zhang, Xiao-Hong; Hu, Xiao-Dan; Zhao, Su-Ying; Xie, Li-Hua; Miao, Yu-Ji; Li, Qun; Min, Rui; Liu, Pei-Dang; Zhang, Hai-Qian

    2016-07-01

    Methemoglobin is an oxidative form of hemoglobin in erythrocytes. The authors' aim was to develop a new biological dosimeter based on a methemoglobin assay. Methemoglobin in peripheral blood (of females or males) that was exposed to a Co source (0.20 Gy min) was quantified using an enzyme-linked immunosorbent assay. The dose range was 0.5-8.0 Gy. In a time-course experiment, the time points 0, 0.02, 1, 2, 3, 7, 15, 21, and 30 d after 4-Gy irradiation of heparinized peripheral blood were used. Methemoglobin levels in a lysed erythrocyte pellet from the irradiated blood of females and males increased with the increasing dose. Methemoglobin levels in female blood irradiated with γ-doses more than 4 Gy were significantly higher than those in male samples at the same doses. Two dose-response relations were fitted to the straight line: one is with the correlation coefficient of 0.98 for females, and the other is with the correlation coefficient of 0.99 for males. The lower limit of dose assessment based on methemoglobin is about 1 Gy. Methemoglobin levels in blood as a result of auto-oxidation increase after 7-d storage at -20 °C. The upregulation of methemoglobin induced by γ-radiation persists for ∼3 d. The absorbed doses that were estimated using the two dose-response relations were close to the actual doses. The results suggest that methemoglobin can be used as a rapid and accurate biological dosimeter for early assessment of absorbed γ-dose in human blood. PMID:27218292

  15. Dose level of occupational exposure in China.

    PubMed

    Tian, Yuan; Zhang, Liang'an; Ju, Yongjian

    2008-01-01

    This paper discusses the dose level of Chinese occupational exposures during 1986-2000. Data on occupational exposures from the main categories in nuclear fuel cycle (uranium enrichment and conversion, fuel fabrication, reactor operation, waste management and research activity, except for uranium mining and milling because of the lack of data), medical uses of radiation (diagnostic radiation, nuclear medicine and radiotherapy) and industrial uses of radiation (industrial radiography and radioisotope production) are presented and summarised in detail. These are the main components of occupational exposures in China. In general, the average annual effective doses show a steady decreasing trend over periods: from 2.16 to 1.16 mSv in medical uses of radiation during 1990-2000; from 1.92 to 1.18 mSv in industrial radiography during 1990-2000; from 8.79 to 2.05 mSv in radioisotope production during the period 1980-2000. Almost all the average annual effective doses in discussed occupations were lower than 5 mSv in recent years (except for well-logging: 6.86 mSv in 1999) and no monitored workers were found to have received the occupational exposure exceeding 50 mSv in a single year or 100 mSv in a five-year period. So the Chinese protection status of occupation exposure has been improved in recent years. However, the average annual effective doses in some occupations, such as diagnostic radiology and coal mining, were still much higher than that of the whole world. There are still needs for further improvement and careful monitoring of occupational exposure to protect every worker from excessive occupational exposure, especially for the workers who were neglected before.

  16. Technical basis for dose reconstruction

    SciTech Connect

    Anspaugh, L.R.

    1996-01-31

    The purpose of this paper is to consider two general topics: technical considerations of why dose-reconstruction studies should or should not be performed and methods of dose reconstruction. The first topic is of general and growing interest as the number of dose-reconstruction studies increases, and one asks the question whether it is necessary to perform a dose reconstruction for virtually every site at which, for example, the Department of Energy (DOE) has operated a nuclear-related facility. And there is the broader question of how one might logically draw the line at performing or not performing dose-reconstruction (radiological and chemical) studies for virtually every industrial complex in the entire country. The second question is also of general interest. There is no single correct way to perform a dose-reconstruction study, and it is important not to follow blindly a single method to the point that cheaper, faster, more accurate, and more transparent methods might not be developed and applied.

  17. Ultraviolet radiation cataract: dose dependence

    NASA Astrophysics Data System (ADS)

    Soderberg, Per G.; Loefgren, Stefan

    1994-07-01

    Current safety limits for cataract development after acute exposure to ultraviolet radiation (UVR) are based on experiments analyzing experimental data with a quantal, effect-no effect, dose-response model. The present study showed that intensity of forward light scattering is better described with a continuous dose-response model. It was found that 3, 30 and 300 kJ/m2UVR300nm induces increased light scattering within 6 h. For all three doses the intensity of forward light scattering was constant after 6 h. The intensity of forward light scattering was proportional to the log dose of UVR300nm. There was a slight increase of the intensity of forward light scattering on the contralateral side in animals that received 300 kJ/m2. Altogether 72 Sprague-Dawley male rats were included. Half of the rats were exposed in vivo on one side to UVR300nm. The other half was kept as a control group, receiving the same treatment as exposed rats but without delivery of UVR300nm to the eye. Subgroups of the rats received either of the three doses. Rats were sacrificed at varying intervals after the exposure. The lenses were extracted and the forward light scattering was estimated. It is concluded that intensity of forward light scattering in the lens after exposure to UVR300nm should be described with a continuous dose-reponse model.

  18. Weldon Spring historical dose estimate

    SciTech Connect

    Meshkov, N.; Benioff, P.; Wang, J.; Yuan, Y.

    1986-07-01

    This study was conducted to determine the estimated radiation doses that individuals in five nearby population groups and the general population in the surrounding area may have received as a consequence of activities at a uranium processing plant in Weldon Spring, Missouri. The study is retrospective and encompasses plant operations (1957-1966), cleanup (1967-1969), and maintenance (1969-1982). The dose estimates for members of the nearby population groups are as follows. Of the three periods considered, the largest doses to the general population in the surrounding area would have occurred during the plant operations period (1957-1966). Dose estimates for the cleanup (1967-1969) and maintenance (1969-1982) periods are negligible in comparison. Based on the monitoring data, if there was a person residing continually in a dwelling 1.2 km (0.75 mi) north of the plant, this person is estimated to have received an average of about 96 mrem/yr (ranging from 50 to 160 mrem/yr) above background during plant operations, whereas the dose to a nearby resident during later years is estimated to have been about 0.4 mrem/yr during cleanup and about 0.2 mrem/yr during the maintenance period. These values may be compared with the background dose in Missouri of 120 mrem/yr.

  19. Correction of the nonlinear dose response improves the viability of adenoviral vectors for gene therapy of Fabry disease.

    PubMed

    Ziegler, Robin J; Li, Chester; Cherry, Maribeth; Zhu, Yunxiang; Hempel, Donna; van Rooijen, Nico; Ioannou, Yiannis A; Desnick, Robert J; Goldberg, Mark A; Yew, Nelson S; Cheng, Seng H

    2002-05-20

    Systemic administration of recombinant adenoviral vectors for gene therapy of chronic diseases such as Fabry disease can be limited by dose-dependent toxicity. Because administration of a high dose of Ad2/CMVHI-alpha gal encoding human alpha-galactosidase A results in expression of supraphysiological levels of the enzyme, we sought to determine whether lower doses would suffice to correct the enzyme deficiency and lysosomal storage abnormality observed in Fabry mice. Reducing the dose of Ad2/CMVHI-alpha gal by 10-fold (from 10(11) to 10(10) particles/mouse) resulted in a greater than 200-fold loss in transgene expression. In Fabry mice, the reduced expression of alpha-galactosidase A, using the lower dose of Ad2/CMVHI-alpha gal, was associated with less than optimal clearance of the accumulated glycosphingolipid (GL-3) from the affected lysosomes. It was determined that this lack of linearity in dose response was not due to an inability to deliver the recombinant viral vectors to the liver but rather to sequestration, at least in part, of the viral vectors by the Kupffer cells. This lack of correlation between dose and expression levels could be obviated by supplementing the low dose of Ad2/CMVHI-alpha gal with an unrelated adenoviral vector or by depleting the Kupffer cells before administration of Ad2/CMVHI-alpha gal. Prior removal of the Kupffer cells, using clodronate liposomes, facilitated the use of a 100-fold lower dose of Ad2/CMVHI-alpha gal (10(9) particles/mouse) to effect the nearly complete clearance of GL-3 from the affected organs of Fabry mice. These results suggest that practical strategies that minimize the interaction between the recombinant adenoviral vectors and the reticuloendothelial system (RES) may improve the therapeutic window of this vector system. In this regard, we showed that pretreatment of mice with gamma globulins also resulted in significantly enhanced adenovirus-mediated transduction and expression of alpha-galactosidase A in the

  20. Monte Carlo Study of Radiation Dose Enhancement by Gadolinium in Megavoltage and High Dose Rate Radiotherapy

    PubMed Central

    Zhang, Daniel G.; Feygelman, Vladimir; Moros, Eduardo G.; Latifi, Kujtim; Zhang, Geoffrey G.

    2014-01-01

    MRI is often used in tumor localization for radiotherapy treatment planning, with gadolinium (Gd)-containing materials often introduced as a contrast agent. Motexafin gadolinium is a novel radiosensitizer currently being studied in clinical trials. The nanoparticle technologies can target tumors with high concentration of high-Z materials. This Monte Carlo study is the first detailed quantitative investigation of high-Z material Gd-induced dose enhancement in megavoltage external beam photon therapy. BEAMnrc, a radiotherapy Monte Carlo simulation package, was used to calculate dose enhancement as a function of Gd concentration. Published phase space files for the TrueBeam flattening filter free (FFF) and conventional flattened 6MV photon beams were used. High dose rate (HDR) brachytherapy with Ir-192 source was also investigated as a reference. The energy spectra difference caused a dose enhancement difference between the two beams. Since the Ir-192 photons have lower energy yet, the photoelectric effect in the presence of Gd leads to even higher dose enhancement in HDR. At depth of 1.8 cm, the percent mean dose enhancement for the FFF beam was 0.38±0.12, 1.39±0.21, 2.51±0.34, 3.59±0.26, and 4.59±0.34 for Gd concentrations of 1, 5, 10, 15, and 20 mg/mL, respectively. The corresponding values for the flattened beam were 0.09±0.14, 0.50±0.28, 1.19±0.29, 1.68±0.39, and 2.34±0.24. For Ir-192 with direct contact, the enhanced were 0.50±0.14, 2.79±0.17, 5.49±0.12, 8.19±0.14, and 10.80±0.13. Gd-containing materials used in MRI as contrast agents can also potentially serve as radiosensitizers in radiotherapy. This study demonstrates that Gd can be used to enhance radiation dose in target volumes not only in HDR brachytherapy, but also in 6 MV FFF external beam radiotherapy, but higher than the currently used clinical concentration (>5 mg/mL) would be needed. PMID:25275550

  1. Monte Carlo study of radiation dose enhancement by gadolinium in megavoltage and high dose rate radiotherapy.

    PubMed

    Zhang, Daniel G; Feygelman, Vladimir; Moros, Eduardo G; Latifi, Kujtim; Zhang, Geoffrey G

    2014-01-01

    MRI is often used in tumor localization for radiotherapy treatment planning, with gadolinium (Gd)-containing materials often introduced as a contrast agent. Motexafin gadolinium is a novel radiosensitizer currently being studied in clinical trials. The nanoparticle technologies can target tumors with high concentration of high-Z materials. This Monte Carlo study is the first detailed quantitative investigation of high-Z material Gd-induced dose enhancement in megavoltage external beam photon therapy. BEAMnrc, a radiotherapy Monte Carlo simulation package, was used to calculate dose enhancement as a function of Gd concentration. Published phase space files for the TrueBeam flattening filter free (FFF) and conventional flattened 6MV photon beams were used. High dose rate (HDR) brachytherapy with Ir-192 source was also investigated as a reference. The energy spectra difference caused a dose enhancement difference between the two beams. Since the Ir-192 photons have lower energy yet, the photoelectric effect in the presence of Gd leads to even higher dose enhancement in HDR. At depth of 1.8 cm, the percent mean dose enhancement for the FFF beam was 0.38±0.12, 1.39±0.21, 2.51±0.34, 3.59±0.26, and 4.59±0.34 for Gd concentrations of 1, 5, 10, 15, and 20 mg/mL, respectively. The corresponding values for the flattened beam were 0.09±0.14, 0.50±0.28, 1.19±0.29, 1.68±0.39, and 2.34±0.24. For Ir-192 with direct contact, the enhanced were 0.50±0.14, 2.79±0.17, 5.49±0.12, 8.19±0.14, and 10.80±0.13. Gd-containing materials used in MRI as contrast agents can also potentially serve as radiosensitizers in radiotherapy. This study demonstrates that Gd can be used to enhance radiation dose in target volumes not only in HDR brachytherapy, but also in 6 MV FFF external beam radiotherapy, but higher than the currently used clinical concentration (>5 mg/mL) would be needed.

  2. Hepatotoxicity of High Oral Dose (-)-Epigallocatechin-3-Gallate in Mice

    PubMed Central

    Lambert, Joshua D.; Kennett, Mary J.; Sang, Shengmin; Reuhl, Kenneth R.; Ju, Jihyeung; Yang, Chung S.

    2009-01-01

    The tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) has been studied for chronic disease preventive effects, and is marketed as part of many dietary supplements. However, case reports have associated the use of green tea-based supplements with liver toxicity. We studied the hepatotoxic effects of high dose EGCG in male CF-1 mice. A single dose of EGCG (1500 mg/kg, i.g.) increased plasma alanine aminotransferase (ALT) by 138-fold and reduced survival by 85%. Once-daily dosing with EGCG increased hepatotoxic response. Plasma ALT levels were increased 184-fold following two once-daily doses of 750 mg/kg, i.g. EGCG. Moderate to severe hepatic necrosis was observed following treatment with EGCG. EGCG hepatotoxicity was associated with oxidative stress including increased hepatic lipid peroxidation (5-fold increase), plasma 8-isoprostane (9.5-fold increase) and increased hepatic metallothionein and γ-histone 2AX protein expression. EGCG also increased plasma interleukin-6 and monocyte chemoattractant protein 1. Our results indicate that higher bolus doses of EGCG are hepatotoxic to mice. Further studies on the dose-dependent hepatotoxic effects of EGCG and the underlying mechanisms are important given the increasing use of green tea dietary supplements, which may deliver much higher plasma and tissue concentrations of EGCG than tea beverages. PMID:19883714

  3. TEAMS: Toxicity- and Efficacy-based Dose Insertion Design with Adaptive Model Selection for Phase I/II Dose-Escalation Trials in Oncology

    PubMed Central

    Guo, Wentian; Ni, Yang; Ji, Yuan

    2015-01-01

    Summary In many oncology clinical trials it is necessary to insert new candidate doses when the prespecified doses are poorly elicited. Formal statistical designs with dose insertion are lacking. We propose a dose insertion design for phase I/II clinical trials in oncology based on both efficacy and toxicity outcomes. We also implement Bayesian model selection during the course of the trial so that better models can be adaptively chosen to achieve more accurate inference. The new design, TEAMS, achieves great operating characteristics in extensive simulation studies due to its ability to adaptively insert new doses as well as perform model selection. As a result, appropriate doses are inserted when necessary and desirable doses are selected with higher probabilities at the end of the trial. PMID:26528377

  4. Effect of Admission Oral Diuretic Dose on Response to Continuous versus Bolus Intravenous Diuretics in Acute Heart Failure: An Analysis from DOSE-AHF

    PubMed Central

    Shah, Ravi V.; McNulty, Steven; O'Connor, Christopher M.; Felker, G. Michael; Braunwald, Eugene; Givertz, Michael M.

    2014-01-01

    Background Results from the Diuretic Optimization Strategies in Acute Heart Failure (DOSE-AHF) study suggest that an initial continuous infusion of loop diuretics is not superior to bolus dosing with regard to clinical endpoints in AHF. We hypothesized that outpatient furosemide dose was associated with congestion and poorer renal function, and explored the hypothesis that a continuous infusion may be more effective in patients on higher outpatient diuretic doses. Methods DOSE-AHF randomized 308 patients within 24 hours of admission to high vs. low initial intravenous diuretic dose given as either a continuous infusion or bolus. We compared baseline characteristics and assessed associations between mode of administration (bolus vs. continuous) and outcomes in patients receiving high-dose (≥120 mg furosemide equivalent, n=177) versus low-dose (<120 mg furosemide equivalent, n=131) outpatient diuretics. Results Patients on higher doses of furosemide were less frequently on renin-angiotensin system inhibitors (P=.01), and had worse renal function and more advanced symptoms. There was a significant interaction between outpatient dose and mode of therapy (P=0.01) with respect to net fluid loss at 72 hours after adjusting for creatinine and intensification strategy. Admission diuretic dose was associated with an increased risk of death or rehospitalization at 60 days (adjusted HR=1.08 per 20-mg increment in dose, 95% CI 1.01–1.16, P=.03). Conclusions In acute HF, patients on higher diuretic doses have greater disease severity, and may benefit from an initial bolus strategy. PMID:23194486

  5. Electrolyte interactions with vapor dosed and solution dosed carbon monoxide on platinum (111)

    NASA Astrophysics Data System (ADS)

    Borup, R. L.; Sauer, D. E.; Stuve, E. M.

    1997-03-01

    Carbon monoxide adsorption and interactions with electrolyte species were examined for a Pt(111) electrode in 0.1M HClO 4. The experiments were conducted with an ex situ ultrahigh vacuum (UHV)-electrochemical system, with CO being adsorbed either from the vapor phase in the vacuum chamber or from solution. CO oxidation coulometry and cyclic voltammetry were used to characterize CO coverage in solution, and thermal desorption spectroscopy was used to measure CO coverage in vacuum, desorption kinetics and to detect coadsorbed electrolyte species. In agreement with earlier studies, the saturation coverage of 0.68 ML of CO from solution dosing is nearly 40% greater than the saturation coverage of 0.50 ML in vacuum at room temperature. The higher saturation coverages survive transfer to vacuum, but only in the presence of coadsorbed electrolyte species (H 2O and ClO 4) retained after removal of the electrode from the electrolyte. In the absence of coadsorbed electrolyte species, saturated, solution dosed CO transferred to vacuum exhibits the same coverage as vapor dosed CO. Interaction between CO and electrolyte species was confirmed through detection of both in thermal desorption following immersion of a vapor dosed CO adlayer into solution and back-transfer to vacuum. Kinetic modeling of CO thermal desorption showed that, regardless of whether CO is adsorbed from solution or from vapor, the COCO repulsive interactions are approximately 40% less when electrolyte species are retained than when they are absent.

  6. Gut microbiota and tacrolimus dosing in kidney transplantation.

    PubMed

    Lee, John R; Muthukumar, Thangamani; Dadhania, Darshana; Taur, Ying; Jenq, Robert R; Toussaint, Nora C; Ling, Lilan; Pamer, Eric; Suthanthiran, Manikkam

    2015-01-01

    Tacrolimus dosing to establish therapeutic levels in recipients of organ transplants is a challenging task because of much interpatient and intrapatient variability in drug absorption, metabolism, and disposition. In view of the reported impact of gut microbial species on drug metabolism, we investigated the relationship between the gut microbiota and tacrolimus dosing requirements in this pilot study of adult kidney transplant recipients. Serial fecal specimens were collected during the first month of transplantation from 19 kidney transplant recipients who either required a 50% increase from initial tacrolimus dosing during the first month of transplantation (Dose Escalation Group, n=5) or did not require such an increase (Dose Stable Group, n=14). We characterized bacterial composition in the fecal specimens by deep sequencing of the PCR amplified 16S rRNA V4-V5 region and we investigated the hypothesis that gut microbial composition is associated with tacrolimus dosing requirements. Initial tacrolimus dosing was similar in the Dose Escalation Group and in the Stable Group (4.2 ± 1.1 mg/day vs. 3.8 ± 0.8 mg/day, respectively, P=0.61, two-way between-group ANOVA using contrasts) but became higher in the Dose Escalation Group than in the Dose Stable Group by the end of the first transplantation month (9.6 ± 2.4 mg/day vs. 3.3 ± 1.5 mg/day, respectively, P<0.001). Our systematic characterization of the gut microbial composition identified that fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was 11.8% in the Dose Escalation Group and 0.8% in the Dose Stable Group (P=0.002, Wilcoxon Rank Sum test, P<0.05 after Benjamini-Hochberg correction for multiple hypotheses). Fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was positively correlated with future tacrolimus dosing at 1 month (R=0.57, P=0.01) and had a coefficient ± standard error of 1.0 ± 0.6 (P=0.08) after multivariable linear regression

  7. Effect of reducing the paediatric stavudine dose by half: a physiologically-based pharmacokinetic model.

    PubMed

    Sy, Sherwin K B; Malmberg, Ruben; Matsushima, Aoi; Asin-Prieto, Eduardo; Rosenkranz, Bernd; Cotton, Mark F; Derendorf, Hartmut; Innes, Steve

    2015-04-01

    Owing to significant dose-related toxicity, the adult stavudine dose was reduced in 2007. The paediatric dose, however, has not been reduced. Although the intended paediatric dose is 1 mg/kg twice daily (b.i.d.), the current weight-band dosing approach results in a mean actual dose of 1.23±0.47 mg/kg. Both efficacy and mitochondrial toxicity depend on the concentration of the intracellular metabolite stavudine triphosphate (d4T-TP). We simulated the effect of reducing the paediatric dose to 0.5 mg/kg. A physiologically-based pharmacokinetic model consisting of 13 tissue compartments plus a full ADAM model was used to describe the elimination of stavudine. The volume of distribution at steady-state and apparent oral clearance were simulated and the resulting AUC profile was compared with literature data in adult and paediatric populations. A biochemical reaction model was utilised to simulate intracellular d4T-TP levels for both the standard and proposed reduced paediatric doses. Simulated and observed exposure after oral dosing showed adequate agreement. Mean steady-state d4T-TP for 1.23 mg/kg b.i.d. was 27.9 (90% CI 27.0-28.9) fmol/10(6) cells, 25% higher than that achieved by the 40 mg adult dose. The 0.5 mg/kg dose resulted in d4T-TP of 13.2 (12.7-13.7) fmol/10(6) cells, slightly higher than the adult dose of 20 mg b.i.d. [11.5 (11.2-11.9) fmol/10(6) cells], which has excellent antiviral efficacy and substantially less toxicity. Current paediatric dosing may result in even higher d4T-TP than the original 40 mg adult dose. Halving the paediatric dose would significantly reduce the risk of mitochondrial toxicity without compromising antiviral efficacy.

  8. Influence of the dosing interval on prolactin release after remoxipride.

    PubMed Central

    Movin-Osswald, G; Hammarlund-Udenaes, M; Von Bahr, C; Eneroth, P; Walton-Bowen, K

    1995-01-01

    1. The prolactin response following administration of the D2-dopamine receptor antagonist remoxipride was studied in eight healthy male volunteers. The purpose of the study was to investigate the duration of a refractory period of prolactin release following two doses of remoxipride. A further aim was to compare the prolactin response following remoxipride and thyrotropin release hormone (TRH) during the refractory period. The subjects received two 30 min intravenous (i.v.) infusions of remoxipride 50 mg with different time intervals between the two doses, in a randomized six period crossover design. The time intervals between the two remoxipride doses were 2, 8, 12, 24 and 48 h. On one occasion the remoxipride dose was followed by an i.v. injection of TRH after 2 h. 2. The plasma peak prolactin concentrations obtained after the first remoxipride dose correspond to a maximal release of prolactin according to earlier studies. A small second peak of prolactin was observed after 2 h. The release was gradually increased with longer time intervals between the consecutive doses. The refractory period for a second prolactin release similar to the first one after remoxipride was found to be 24 h for most of the subjects. 3. TRH resulted in a faster and higher increase in prolactin response of a shorter duration than after remoxipride administered 2 h after the first dose. PMID:7669486

  9. Absorbed dose simulations in near-surface regions using high dose rate Iridium-192 sources applied for brachytherapy

    NASA Astrophysics Data System (ADS)

    Moura, E. S.; Zeituni, C. A.; Sakuraba, R. K.; Gonçalves, V. D.; Cruz, J. C.; Júnior, D. K.; Souza, C. D.; Rostelato, M. E. C. M.

    2014-02-01

    Brachytherapy treatment with Iridium-192 high dose rate (HDR) sources is widely used for various tumours and it could be developed in many anatomic regions. Iridium-192 sources are inserted inside or close to the region that will be treated. Usually, the treatment is performed in prostate, gynaecological, lung, breast and oral cavity regions for a better clinical dose coverage compared with other techniques, such as, high energy photons and Cobalt-60 machines. This work will evaluate absorbed dose distributions in near-surface regions around Ir-192 HDR sources. Near-surface dose measurements are a complex task, due to the contribution of beta particles in the near-surface regions. These dose distributions should be useful for non-tumour treatments, such as keloids, and other non-intracavitary technique. For the absorbed dose distribution simulations the Monte Carlo code PENELOPE with the general code penEasy was used. Ir-192 source geometry and a Polymethylmethacrylate (PMMA) tube, for beta particles shield were modelled to yield the percentage depth dose (PDD) on a cubic water phantom. Absorbed dose simulations were realized at the central axis to yield the Ir-192 dose fall-off along central axis. The results showed that more than 99.2% of the absorbed doses (relative to the surface) are deposited in 5 cm depth but with slower rate at higher distances. Near-surface treatments with Ir-192 HDR sources yields achievable measurements and with proper clinical technique and accessories should apply as an alternative for treatment of lesions where only beta sources were used.

  10. Total dose responses and reliability issues of 65 nm NMOSFETs

    NASA Astrophysics Data System (ADS)

    Dezhao, Yu; Qiwen, Zheng; Jiangwei, Cui; Hang, Zhou; Xuefeng, Yu; Qi, Guo

    2016-06-01

    In this paper, total dose responses and reliability issues of MOSFETs fabricated by 65 nm CMOS technology were examined. “Radiation-induced narrow channel effect” is observed in a narrow channel device. Similar to total dose responses of NMOSFETs, narrow channel NMOSFEs have larger hot-carrier-induced degradation than wide channel devices. Step Time-Dependent Dielectric Breakdown (TDDB) stresses are applied, and narrow channel devices have higher breakdown voltage than wide channel devices, which agree with “weakest link” theory of TDDB. Experimental results show that linear current, transconductance, saturated drain current and subthreshold swing are superposed degenerated by total dose irradiation and reliability issues, which may result in different lifetime from that considering total dose irradiation reliability issues separately. Project supported by “Light of West China” Program of CAS (No. XBBS201219).

  11. VMATc: VMAT with constant gantry speed and dose rate

    NASA Astrophysics Data System (ADS)

    Peng, Fei; Jiang, Steve B.; Romeijn, H. Edwin; Epelman, Marina A.

    2015-04-01

    This article considers the treatment plan optimization problem for Volumetric Modulated Arc Therapy (VMAT) with constant gantry speed and dose rate (VMATc). In particular, we consider the simultaneous optimization of multi-leaf collimator leaf positions and a constant gantry speed and dose rate. We propose a heuristic framework for (approximately) solving this optimization problem that is based on hierarchical decomposition. Specifically, an iterative algorithm is used to heuristically optimize dose rate and gantry speed selection, where at every iteration a leaf position optimization subproblem is solved, also heuristically, to find a high-quality plan corresponding to a given dose rate and gantry speed. We apply our framework to clinical patient cases, and compare the resulting VMATc plans to idealized IMRT, as well as full VMAT plans. Our results suggest that VMATc is capable of producing treatment plans of comparable quality to VMAT, albeit at the expense of long computation time and generally higher total monitor units.

  12. radir package: an R implementation for cytogenetic biodosimetry dose estimation.

    PubMed

    Moriña, David; Higueras, Manuel; Puig, Pedro; Ainsbury, Elizabeth A; Rothkamm, Kai

    2015-09-01

    The Bayesian framework has been shown to be very useful in cytogenetic dose estimation. This approach allows description of the probability of an event in terms of previous knowledge, e.g. its expectation and/or its uncertainty. A new R package entitled radir (radiation inverse regression) has been implemented with the aim of reproducing a recent Bayesian-type dose estimation methodology. radir adopts the method of dose estimation under the Poisson assumption of the responses (the chromosomal aberrations counts) for the required dose-response curve (typically linear or quadratic). The individual commands are described in detail and relevant examples of the use of the methods and the corresponding radir software tools are given. The suitability of this methodology is highlighted and its application encouraged by providing a user-friendly command-type software interface within the R statistical software (version 3.1.1 or higher), which includes a complete manual.

  13. Fast reconstruction of low dose proton CT by sinogram interpolation

    NASA Astrophysics Data System (ADS)

    Hansen, David C.; Sangild Sørensen, Thomas; Rit, Simon

    2016-08-01

    Proton computed tomography (CT) has been demonstrated as a promising image modality in particle therapy planning. It can reduce errors in particle range calculations and consequently improve dose calculations. Obtaining a high imaging resolution has traditionally required computationally expensive iterative reconstruction techniques to account for the multiple scattering of the protons. Recently, techniques for direct reconstruction have been developed, but these require a higher imaging dose than the iterative methods. No previous work has compared the image quality of the direct and the iterative methods. In this article, we extend the methodology for direct reconstruction to be applicable for low imaging doses and compare the obtained results with three state-of-the-art iterative algorithms. We find that the direct method yields comparable resolution and image quality to the iterative methods, even at 1 mSv dose levels, while yielding a twentyfold speedup in reconstruction time over previously published iterative algorithms.

  14. Low-dose radiation: a cause of breast cancer

    SciTech Connect

    Land, C.E.

    1980-08-15

    It is likely that the breast is the organ most sensitive to radiation carcinogenesis in postpubertal women. Studies of different exposed populations have yielded remarkably consistent results, in spite of wide differences in underlying breast cancer rates and conditions of exposure. Excess risk is approximately proportional to dose, and is relatively independent of ionization density and fractionization of dose. This implies that the risk associated with low-dose exposures to ionizing radiation can be estimated with some confidence from higher-dose data. Excess risk is heavily dependent on age at exposure but relatively independent of population differences in normal risk. The temporal patterns after exposure of both radiation-induced and naturally occurring breast cancer are similar, suggesting a strong influence of factors other than radiation on radiation-induced breast cancer. Uncertainties remain about risks from exposures before puberty and after menopause.

  15. Dose and dose rate effectiveness of space radiation.

    PubMed

    Schimmerling, W; Cucinotta, F A

    2006-01-01

    Dose and dose rate effectiveness factors (DDREF), in conjunction with other weighting factors, are commonly used to scale atomic bomb survivor data in order to establish limits for occupational radiation exposure, including radiation exposure in space. We use some well-known facts about the microscopic pattern of energy deposition of high-energy heavy ions, and about the dose rate dependence of chemical reactions initiated by radiation, to show that DDREF are likely to vary significantly as a function of particle type and energy, cell, tissue, and organ type, and biological end point. As a consequence, we argue that validation of DDREF by conventional methods, e.g. irradiating animal colonies and compiling statistics of cancer mortality, is not appropriate. However, the use of approaches derived from information theory and thermodynamics is a very wide field, and the present work can only be understood as a contribution to an ongoing discussion. PMID:17169950

  16. Radiological dose assessment for vault storage concepts

    SciTech Connect

    Richard, R.F.

    1997-02-25

    This radiological dose assessment presents neutron and photon dose rates in support of project W-460. Dose rates are provided for a single 3013 container, the ``infloor`` storage vault concept, and the ``cubicle`` storage vault concept.

  17. Chronic uranium exposure dose-dependently induces glutathione in rats without any nephrotoxicity.

    PubMed

    Poisson, C; Stefani, J; Manens, L; Delissen, O; Suhard, D; Tessier, C; Dublineau, I; Guéguen, Y

    2014-10-01

    Uranium is a heavy metal naturally found in the earth's crust that can contaminate the general public population when ingested. The acute effect and notably the uranium nephrotoxicity are well known but knowledge about the effect of chronic uranium exposure is less clear. In a dose-response study we sought to determine if a chronic exposure to uranium is toxic to the kidneys and the liver, and what the anti-oxidative system plays in these effects. Rats were contaminated for 3 or 9 months by uranium in drinking water at different concentrations (0, 1, 40, 120, 400, or 600 mg/L). Uranium tissue content in the liver, kidneys, and bones was linear and proportional to uranium intake after 3 and 9 months of contamination; it reached 6 μg per gram of kidney tissues for the highest uranium level in drinking water. Nevertheless, no histological lesions of the kidney were observed, nor any modification of kidney biomarkers such as creatinine or KIM-1. After 9 months of contamination at and above the 120-mg/L concentration of uranium, lipid peroxidation levels decreased in plasma, liver, and kidneys. Glutathione concentration increased in the liver for the 600-mg/L group, in the kidney it increased dose dependently, up to 10-fold, after 9 months of contamination. Conversely, chronic uranium exposure irregularly modified gene expression of antioxidant enzymes and activities in the liver and kidneys. In conclusion, chronic uranium exposure did not induce nephrotoxic effects under our experimental conditions, but instead reinforced the antioxidant system, especially by increasing glutathione levels in the kidneys.

  18. Dose calculation for electron therapy

    NASA Astrophysics Data System (ADS)

    Gebreamlak, Wondesen T.

    The dose delivered by electron beams has a complex dependence on the shape of the field; any field shaping shields, design of collimator systems, and energy of the beam. This complicated dependence is due to multiple scattering of the electron beam as the beam travels from the accelerator head to the patient. The dosimetry of only regular field shapes (circular, square, or rectangular) is well developed. However, most tumors have irregular shapes and their dosimetry is calculated by direct measurement. This is laborious and time consuming. In addition, error can be introduced during measurements. The lateral build up ratio method (LBR), which is based on the Fermi-Eyges multiple scattering theory, calculates the dosimetry of irregular electron beam shapes. The accuracy of this method depends on the function sigma r(r,E) (the mean square radial displacement of the electron beam in the medium) used in the calculation. This research focuses on improving the accuracy of electron dose calculations using lateral build up ratio method by investigating the properties of sigmar(r,E). The percentage depth dose curves of different circular cutouts were measured using four electron beam energies (6, 9, 12, and 15 MeV), four electron applicator sizes (6x6, 10x10, 14x14, and 20x20 cm), three source-surface distance values (100, 105, 110 cm). The measured percentage depth dose curves were normalized at a depth of 0.05 cm. Using the normalized depth dose, the lateral build up ratio curves were determined. Using the cutout radius and the lateral build up ratio values, sigmar(z,E) were determined. It is shown that the sigma value increases linearly with cutout size until the cutout radius reaches the equilibrium range of the electron beam. The sigma value of an arbitrary circular cutout was determined from the interpolation of sigma versus cutout curve. The corresponding LBR value of the circular cutout was determined using its radius and sigma values. The depth dose distribution of

  19. Simulation studies on the effect of absorbers on dose distribution in rotational radiotherapy.

    PubMed

    Ivanova, T; Bliznakova, K; Malatara, G; Kardamakis, D; Kolitsi, Z; Pallikarakis, N

    2009-12-01

    The effect of cylindrical protector dimensions, material and distance from the source on the dose distribution in rotational radiotherapy was studied to assess the potential protection possibilities of small-sized radiosensitive structures, such as spinal cord. The dose distributions were evaluated in terms of dose at the protected region and surface dose, ratio of the dose at the protected region to the maximum dose, and dose gradient. High-density materials, such as lead, tungsten, gold and cerrobend, along with new polymer-metal composite ones were used in simulation studies, performed by an in-house developed Monte Carlo Radiotherapy Simulator. To ensure correct modeling of the composite materials, simulated attenuation data were verified against experimentally measured data. The dependence of the dose at the protected region from the protector diameter and the field size was established. Protectors of higher density and larger diameter provide not only lower dose at the protected region, but also steeper dose gradient and lower ratio of the dose at the protected region to the treatment dose. For the protection of small structures, high-density protectors placed further from the source allow thicker protectors to be used. The surface dose increases insignificantly for the studied protector-surface distances. The results have shown that shielding properties of composite materials are close to those of lead. PMID:19186088

  20. A Bayesian Dose-finding Design for Oncology Clinical Trials of Combinational Biological Agents

    PubMed Central

    Cai, Chunyan; Yuan, Ying; Ji, Yuan

    2013-01-01

    Treating patients with novel biological agents is becoming a leading trend in oncology. Unlike cytotoxic agents, for which efficacy and toxicity monotonically increase with dose, biological agents may exhibit non-monotonic patterns in their dose-response relationships. Using a trial with two biological agents as an example, we propose a dose-finding design to identify the biologically optimal dose combination (BODC), which is defined as the dose combination of the two agents with the highest efficacy and tolerable toxicity. A change-point model is used to reflect the fact that the dose-toxicity surface of the combinational agents may plateau at higher dose levels, and a flexible logistic model is proposed to accommodate the possible non-monotonic pattern for the dose-efficacy relationship. During the trial, we continuously update the posterior estimates of toxicity and efficacy and assign patients to the most appropriate dose combination. We propose a novel dose-finding algorithm to encourage sufficient exploration of untried dose combinations in the two-dimensional space. Extensive simulation studies show that the proposed design has desirable operating characteristics in identifying the BODC under various patterns of dose-toxicity and dose-efficacy relationships. PMID:24511160

  1. A Bayesian Dose-finding Design for Oncology Clinical Trials of Combinational Biological Agents.

    PubMed

    Cai, Chunyan; Yuan, Ying; Ji, Yuan

    2014-01-01

    Treating patients with novel biological agents is becoming a leading trend in oncology. Unlike cytotoxic agents, for which efficacy and toxicity monotonically increase with dose, biological agents may exhibit non-monotonic patterns in their dose-response relationships. Using a trial with two biological agents as an example, we propose a dose-finding design to identify the biologically optimal dose combination (BODC), which is defined as the dose combination of the two agents with the highest efficacy and tolerable toxicity. A change-point model is used to reflect the fact that the dose-toxicity surface of the combinational agents may plateau at higher dose levels, and a flexible logistic model is proposed to accommodate the possible non-monotonic pattern for the dose-efficacy relationship. During the trial, we continuously update the posterior estimates of toxicity and efficacy and assign patients to the most appropriate dose combination. We propose a novel dose-finding algorithm to encourage sufficient exploration of untried dose combinations in the two-dimensional space. Extensive simulation studies show that the proposed design has desirable operating characteristics in identifying the BODC under various patterns of dose-toxicity and dose-efficacy relationships. PMID:24511160

  2. Cord Dose Specification and Validation for Stereotactic Body Radiosurgery of Spine

    SciTech Connect

    Li Shidong Liu Yan; Chen Qing; Jin Jianyue

    2009-01-01

    Effective dose to a portion of the spinal cord in treatment segment, rather than the maximum point dose in the cord surface, was set as the dose limit in stereotactic-body radiosurgery (SBRS) of spine. Such a cord dose specification is sensitive to the volume size and position errors. Thus, we used stereotactic image guidance to minimize phantom positioning errors and compared the results of a 0.6-cm{sup 3} Farmer ionization chamber and a 0.01-cm{sup 3} compact ionization chamber to determine the detector size effect on 9 SBRS cases. The experimental errors ranging from 2% to 7% were estimated by the deviation of the mean dose in plans to the chamber with spatial displacements of 0.5 mm. The mean and measured doses for the large chamber to individual cases were significantly ({approx}17%) higher than the doses with the compact chamber placed at the same point. Our experimental results shown that the mean doses to the volume of interest could represent the measured cord doses. For the 9 patients, the mean doses to 10% of the cord were about 10 Gy, while the maximum cord doses varied from 11.6 to 17.6 Gy. The mean dose, possibly correlated with the cord complication, provided us an alternative and reliable cord dose specification in SBRS of spine.

  3. Hanford Environmental Dose Reconstruction Project

    SciTech Connect

    Finch, S. M.; McMakin, A. H.

    1991-09-01

    The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation dose that individuals and populations could have received from nuclear operations at Hanford since 1944. The project is divided into five technical tasks. These tasks correspond to the path radionuclides followed, from release to impact on humans (i.e., dose estimates). The Source Terms Task develops estimates of radioactive emissions from Hanford facilities since 1944. The Environmental Transport Task reconstructs the movements of radioactive particles from the areas of release to populations. The Environmental Monitoring Data Task assemblies, evaluates and reports historical environmental monitoring data. The Demographics, Agriculture and Food Habits Task develops the data needed to identify the populations that could have been affected by the releases. The Environmental Pathways and Dose Estimates Task used the information derived from the other Tasks to estimate the radiation doses individuals could have received from Hanford radiation. This document lists the progress on this project as of September 1991. 3 figs., 2 tabs.

  4. Hanford Environmental Dose Reconstruction Project

    SciTech Connect

    Finch, S.M.

    1990-01-01

    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 being managed and conducted by the Pacific Northwest Laboratory (PNL) under the direction of an independent Technical Steering Panel (TSP). 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). The Source Terms Task develops estimates of radioactive emissions from Hanford facilities since 1944. The Environmental Transport Task reconstructs the movement of radioactive materials from the areas of release to populations. The Environmental Monitoring Data Task assembles, evaluates, and reports historical environmental monitoring data. The Demographics, Agriculture, Food Habits Task develops the data needed to identify the populations that could have been affected by the releases. In addition to population and demographic data, the food and water resources and consumption patterns for populations are estimated because they provide a primary pathway for the intake of radionuclides. The Environmental Pathways and Dose Estimates Task use the information produced by the other tasks to estimate the radiation doses populations could have received from Hanford radiation. Project progress is documented in this monthly report, which is available to the public. 3 figs., 3 tabs.

  5. AGING FACILITY WORKER DOSE ASSESSMENT

    SciTech Connect

    R.L. Thacker

    2005-03-24

    The purpose of this calculation is to estimate radiation doses received by personnel working in the Aging Facility performing operations to transfer aging casks to the aging pads for thermal and logistical management, stage empty aging casks, and retrieve aging casks from the aging pads for further processing in other site facilities. Doses received by workers due to aging cask surveillance and maintenance operations are also included. 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 from normal operation. There are no Category 1 event sequences associated with the Aging Facility (BSC 2004 [DIRS 167268], Section 7.2.1). The results of this calculation will be used to support the design of the Aging Facility and to provide occupational dose estimates for the License Application. The calculations contained in this document were developed by Environmental and Nuclear Engineering of the Design and Engineering Organization and are intended solely for the use of the Design and Engineering Organization in its work regarding facility operation. Yucca Mountain Project personnel from the Environmental and Nuclear Engineering should be consulted before use of the calculations for purposes other than those stated herein or use by individuals other than authorized personnel in Environmental and Nuclear Engineering.

  6. Biological doses with template distribution patterns

    SciTech Connect

    Harrop, R.; Haymond, H.R.; Nisar, A.; Syed, A.N.M.; Feder, B.H.; Neblett, D.L.

    1981-02-01

    Consideration of radiation dose rate effects emphasizes advantages of the template method for lateral distribution of multiple sources in treatment of laterally infiltrating gynecologic cancer, when compared to a conventional technique with colpostats. Biological doses in time dose fractionation (TDF), ret and reu units are calculated for the two treatment methods. With the template method the lateral dose (point B) is raised without significantly increasing the doses to the rectum and bladder, that is, relatively, the calculated biological doses at point A and B are more nearly equivalent and the doses to the rectum and bladder are significantly lower than the dose to point B.

  7. Dose reconstruction for real-time patient-specific dose estimation in CT

    SciTech Connect

    De Man, Bruno Yin, Zhye; Wu, Mingye; FitzGerald, Paul; Kalra, Mannudeep

    2015-05-15

    Purpose: Many recent computed tomography (CT) dose reduction approaches belong to one of three categories: statistical reconstruction algorithms, efficient x-ray detectors, and optimized CT acquisition schemes with precise control over the x-ray distribution. The latter category could greatly benefit from fast and accurate methods for dose estimation, which would enable real-time patient-specific protocol optimization. Methods: The authors present a new method for volumetrically reconstructing absorbed dose on a per-voxel basis, directly from the actual CT images. The authors’ specific implementation combines a distance-driven pencil-beam approach to model the first-order x-ray interactions with a set of Gaussian convolution kernels to model the higher-order x-ray interactions. The authors performed a number of 3D simulation experiments comparing the proposed method to a Monte Carlo based ground truth. Results: The authors’ results indicate that the proposed approach offers a good trade-off between accuracy and computational efficiency. The images show a good qualitative correspondence to Monte Carlo estimates. Preliminary quantitative results show errors below 10%, except in bone regions, where the authors see a bigger model mismatch. The computational complexity is similar to that of a low-resolution filtered-backprojection algorithm. Conclusions: The authors present a method for analytic dose reconstruction in CT, similar to the techniques used in radiation therapy planning with megavoltage energies. Future work will include refinements of the proposed method to improve the accuracy as well as a more extensive validation study. The proposed method is not intended to replace methods that track individual x-ray photons, but the authors expect that it may prove useful in applications where real-time patient-specific dose estimation is required.

  8. 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).

  9. Radiation dose from reentrant electrons.

    PubMed

    Badhwar, G D; Watts, J; Cleghorn, T E

    2001-06-01

    In estimating the crew exposures during an extra vehicular activity (EVA), the contribution of reentrant electrons has always been neglected. Although the flux of these electrons is small compared to the flux of trapped electrons, their energy spectrum extends to several GeV compared to about 7 MeV for trapped electrons. This is also true of splash electrons. Using the measured reentrant electron energy spectra, it is shown that the dose contribution of these electrons to the blood forming organs (BFO) is more that 10 times greater than that from the trapped electrons. The calculations also show that the dose-depth response is a very slowly changing function of depth, and thus adding reasonable amounts of additional shielding would not significantly lower the dose to BFO. PMID:11855420

  10. Radiation Dose from Reentrant Electrons

    NASA Technical Reports Server (NTRS)

    Badhwar, G.D.; Cleghorn, T. E.; Watts, J.

    2003-01-01

    In estimating the crew exposures during an EVA, the contribution of reentrant electrons has always been neglected. Although the flux of these electrons is small compared to the flux of trapped electrons, their energy spectrum extends to several GeV compared to about 7 MeV for trapped electrons. This is also true of splash electrons. Using the measured reentrant electron energy spectra, it is shown that the dose contribution of these electrons to the blood forming organs (BFO) is more than 10 times greater than that from the trapped electrons. The calculations also show that the dose-depth response is a very slowly changing function of depth, and thus adding reasonable amounts of additional shielding would not significantly lower the dose to BFO.

  11. In vivo and phantom measurements versus Eclipse TPS prediction of near surface dose for SBRT treatments

    NASA Astrophysics Data System (ADS)

    Cho, Gwi A.; Ralston, Anna; Tin, Mo Mo; Martin, Darren; Pickard, Sheila; Kim, J.-H.; Tse, Regina

    2014-03-01

    This study reports on Gafchromic EBT2 film skin dose measurements for lung stereotactic body radiotherapy. These measurements were compared to near surface skin doses predicted by Eclipse treatment planning system (TPS) using the Analytical Anisotropic Algorithm (AAA) for a 6 MV photon beam. The accuracy of the predicted near surface dose for 3×3, 5×5 and 10×10 cm2 fields was assessed using an Attix chamber and EBT2 film in a Virtual Water phantom and compared to Monte Carlo calculation. The maximum near surface dose and its location were identified from the patient's treatment plan. For phantom measurements, the TPS dose (nominal 0 mm depth) was higher than the Attix chamber data by up to 24.0 % but in closer agreement with the EBT2 film measurement, which was up to 10.3 % higher than the Attix data. The MC calculated dose values were higher than the Attix data by up to 3.5% for the depths up to 2 mm. The maximum patient skin dose estimated from in vivo EBT2 film measurements was 7.5 - 19.5 Gy per course and depended on the number of overlapping fields, beam weight and/or contact with immobilisation devices. The TPS predicted dose for patient plans was mostly higher than the in vivo dose, by as much as 69.3%, but in two cases was lower, by as much as -23.1%.

  12. The Effect of Patient Weight and Provider Training and Experience on Dosing of Rocuronium

    PubMed Central

    Rodriguez, L.; Banks, S.; Major, B. T.; Rodriguez, Y.

    2016-01-01

    Introduction. Maintenance dosing of neuromuscular blocking agents is complex and varies with patient, procedure, and clinical situation. With this in mind, we sought to identify factors impacting the maintenance dosing of neuromuscular blockers as a step toward identifying best practice with respect to minimizing residual neuromuscular blockade. Methods. Cases utilizing rocuronium from July 1, 2010, to June 30, 2014, at the sponsoring institution were analyzed. Using a mixed model to account for repeated measures, patients were analyzed by dose and weight category as defined by the World Health Organization (eight categories ranging from very severely underweight to very severely obese) as well as by the administering provider's level of experience. Results. The study included 12,671 patients with a mean age of 49.7 (SD 16.7). Increasing weight category and higher levels of provider experience were associated with higher doses for rocuronium. There were no differences in initial dose or in frequency of maintenance dosing by weight category after controlling for case length. Discussion. The two dosing patterns identified, higher doses for overweight patients and higher doses administered by experienced providers, are modifiable factors that could enhance patient safety. PMID:27429615

  13. The Effect of Patient Weight and Provider Training and Experience on Dosing of Rocuronium.

    PubMed

    Godwin, N C; Rodriguez, L; Banks, S; Major, B T; Rodriguez, Y

    2016-01-01

    Introduction. Maintenance dosing of neuromuscular blocking agents is complex and varies with patient, procedure, and clinical situation. With this in mind, we sought to identify factors impacting the maintenance dosing of neuromuscular blockers as a step toward identifying best practice with respect to minimizing residual neuromuscular blockade. Methods. Cases utilizing rocuronium from July 1, 2010, to June 30, 2014, at the sponsoring institution were analyzed. Using a mixed model to account for repeated measures, patients were analyzed by dose and weight category as defined by the World Health Organization (eight categories ranging from very severely underweight to very severely obese) as well as by the administering provider's level of experience. Results. The study included 12,671 patients with a mean age of 49.7 (SD 16.7). Increasing weight category and higher levels of provider experience were associated with higher doses for rocuronium. There were no differences in initial dose or in frequency of maintenance dosing by weight category after controlling for case length. Discussion. The two dosing patterns identified, higher doses for overweight patients and higher doses administered by experienced providers, are modifiable factors that could enhance patient safety.

  14. A comparison of quantum limited dose and noise equivalent dose

    NASA Astrophysics Data System (ADS)

    Job, Isaias D.; Boyce, Sarah J.; Petrillo, Michael J.; Zhou, Kungang

    2016-03-01

    Quantum-limited-dose (QLD) and noise-equivalent-dose (NED) are performance metrics often used interchangeably. Although the metrics are related, they are not equivalent unless the treatment of electronic noise is carefully considered. These metrics are increasingly important to properly characterize the low-dose performance of flat panel detectors (FPDs). A system can be said to be quantum-limited when the Signal-to-noise-ratio (SNR) is proportional to the square-root of x-ray exposure. Recent experiments utilizing three methods to determine the quantum-limited dose range yielded inconsistent results. To investigate the deviation in results, generalized analytical equations are developed to model the image processing and analysis of each method. We test the generalized expression for both radiographic and fluoroscopic detectors. The resulting analysis shows that total noise content of the images processed by each method are inherently different based on their readout scheme. Finally, it will be shown that the NED is equivalent to the instrumentation-noise-equivalent-exposure (INEE) and furthermore that the NED is derived from the quantum-noise-only method of determining QLD. Future investigations will measure quantum-limited performance of radiographic panels with a modified readout scheme to allow for noise improvements similar to measurements performed with fluoroscopic detectors.

  15. Increasing maximum tumor dose to manage range uncertainties in IMPT treatment planning

    NASA Astrophysics Data System (ADS)

    Petit, Steven; Seco, Joao; Kooy, Hanne

    2013-10-01

    The accuracy of intensity modulated proton therapy (IMPT) is sensitive to range uncertainties. Geometric margins, as dosimetric surrogates, are ineffective and robust optimization strategies are needed. These, however, lead to increased normal tissue dose. We explore here how this dose increase can be reduced by increasing the maximum tumor dose instead. We focus on range uncertainties, modeled by scaling the stopping powers 5% up (undershoot) or down (overshoot) compared to the nominal scenario. Robust optimization optimizes for target dose conformity in the most likely scenario, not the worst, while constraining target coverage for the worst-case scenario. Non-robust plans are also generated. Different maximum target doses are applied (105% versus 120% versus 140%) to investigate the effect on normal tissue dose reduction. The method is tested on a homogeneous and a lung phantom and on a liver patient. Target D99 of the robust plans equals the prescription dose of 60 GyEWe use the symbol GyE for the correct notation of Gy(RBE). for all scenarios, but decreases to 36 GyE for the non-robust plans. The mean normal tissue dose in a 2 cm ring around the target is 11% to 31% higher for the robust plans. This increase can be reduced to -8% and 3% (compared to the non-robust plan) by allowing a maximum tumor dose of 120% instead of 105%. Thus robustness leads to more normal tissue dose, but it can be compensated by allowing a higher maximum tumor dose.

  16. State Intervention in Higher Education.

    ERIC Educational Resources Information Center

    Glenny, Lyman A.; Bowen, Frank M.

    State intervention in higher education is discussed, and state and federal regulations that affect higher education are discussed and contrasted. The structures and procedures by which states intervene in higher education are outlined, and the issue of institutional autonomy is considered. Policy areas through which the state can affect higher…

  17. Advancing Diversity in Higher Education

    ERIC Educational Resources Information Center

    Turner, Caroline S.

    2013-01-01

    This special section of the "Journal of Diversity in Higher Education" ("JDHE") on "Advancing Diversity in Higher Education" emerged from the 2012 Association for the Study of Higher Education Council on Ethnic Participation (ASHE-CEP) Pre-Conference Forum. CEP, a standing committee of ASHE, partnered with the…

  18. Capital Formation in Higher Education.

    ERIC Educational Resources Information Center

    Frances, Carol; Coldren, Sharon L.

    The need for new capital in higher education and major areas where the interests of the business and higher education communities are aligned are considered. Higher education is a major employer and makes a large contribution to the gross national product. Human capital has become the accepted term for referring to the contribution of education,…

  19. Higher Education Finance Manual 1975.

    ERIC Educational Resources Information Center

    Collier, Douglas J.; Mertins, Paul J.

    The Higher Education Finance Manual (HEFM) is intended to serve as a guide to higher education planners and managers in their understanding and use of institutional finance data. It addresses higher education finance data from the layman's perspective. The document includes definitions of accounting terms and descriptions of generally accepted…

  20. A Tax for Higher Education

    ERIC Educational Resources Information Center

    Blumenstyk, Goldie

    2012-01-01

    Higher education pays off handsomely for society. Yet on a nationwide basis, states' support for higher education per full-time-equivalent student has fallen to just $6,290, the lowest in 15 years. A dedicated source of funds for higher education is problematic. But what if state and federal lawmakers applied the impeccable logic of the gas tax to…

  1. Internationalization of Chinese Higher Education

    ERIC Educational Resources Information Center

    Chen, Linhan; Huang, Danyan

    2013-01-01

    This paper probes into the development of internationalization of higher education in China from ancient times to modern times, including the emergence of international connections in Chinese higher education and the subsequent development of such connections, the further development of internationalization of Chinese higher education, and the…

  2. Commitment to Higher Vocational Education.

    ERIC Educational Resources Information Center

    Imrie, Brad; And Others

    This publication is a history of the College of Higher Vocational Studies (CHVS) since it was established in 1991 and provides commentary on developments in higher vocational education in Hong Kong during a period of unprecedented change and development in the provision of the Higher Diploma. "Principal's Diary" (Bradford Imrie) describes the…

  3. Higher Education Studies in Japan

    ERIC Educational Resources Information Center

    Kaneko, Motohisa

    2010-01-01

    The rapid development of higher education in the postwar period has given rise to various problems, and higher education studies in Japan have developed in response to them. What have been the major issues, and how did academic research respond to them, in postwar Japan? This article delineates an outline of higher education studies in general,…

  4. Higher Education and Public Good

    ERIC Educational Resources Information Center

    Marginson, Simon

    2011-01-01

    Policy debate about whether to maintain public subsidies for higher education has stimulated reconsideration of the public mission of higher education institutions, especially those that provide student places conferring private benefits. If the work of higher education institutions is defined simply as the aggregation of private interests, this…

  5. People Who Study Higher Education

    ERIC Educational Resources Information Center

    Harland, Tony

    2009-01-01

    The study of higher education can seem extraordinarily complex because what counts as knowledge is contestable and the higher education research community is, like Hemingway's Paris, a moveable feast. A lack of epistemological precision and field uncertainty is partly due to the fact that those who study higher education tend to work in higher…

  6. Emerging Trends in Higher Education.

    ERIC Educational Resources Information Center

    Fife, Jonathan D.; Barnett, Lynn

    Trends and projections for higher education are identified. Increased public concern about the purposes and standards of higher education has followed the publication of four major publications about higher education in the United States. Changing demographics are projected for 1983-1993, including fewer 18- to 22-year-olds, decreased full-time…

  7. Higher Education in the Eighties.

    ERIC Educational Resources Information Center

    McComas, James D.

    Events and conditions over the last 20 years that have altered the course of higher education are briefly noted, and trends in higher education for the early eighties are examined. Among the past influences on higher education that illustrate the wisdom of planning for a realistic period of time, such as five years, are the following: the massive…

  8. History of Higher Education, 1992.

    ERIC Educational Resources Information Center

    History of Higher Education, 1992

    1992-01-01

    This annual compilation offers six articles on the history of higher education. In the first article, "The Historical Matrix of American Higher Education," Roger L. Geiger provides an overview of the history of American higher education. Following it, E. D. Duryea, Jurgen Herbst, and W. Bruce Leslie comment on his hypothesis which identifies eight…

  9. Survey of clinical doses from computed tomography examinations in the Canadian province of Manitoba.

    PubMed

    A Elbakri, Idris; D C Kirkpatrick, Iain

    2013-12-01

    The purpose of this study was to document CT doses for common CT examinations performed throughout the province of Manitoba. Survey forms were sent out to all provincial CT sites. Thirteen out of sixteen (81 %) sites participated. The authors assessed scans of the brain, routine abdomen-pelvis, routine chest, sinuses, lumbar spine, low-dose lung nodule studies, CT pulmonary angiograms, CT KUBs, CT colonographies and combination chest-abdomen-pelvis exams. Sites recorded scanner model, protocol techniques and patient and dose data for 100 consecutive patients who were scanned with any of the aforementioned examinations. Mean effective doses and standard deviations for the province and for individual scanners were computed. The Kruskal-Wallis test was used to compare the variability of effective doses amongst scanners. The t test was used to compare doses and their provincial ranges between newer and older scanners and scanners that used dose saving tools and those that did not. Abdomen-pelvis, chest and brain scans accounted for over 70 % of scans. Their mean effective doses were 18.0 ± 6.7, 13.2 ± 6.4 and 3.0 ± 1.0 mSv, respectively. Variations in doses amongst scanners were statistically significant. Most examinations were performed at 120 kVp, and no lower kVp was used. Dose variations due to scanner age and use of dose saving tools were not statistically significant. Clinical CT doses in Manitoba are broadly similar to but higher than those reported in other Canadian provinces. Results suggest that further dose reduction can be achieved by modifying scanning techniques, such as using lower kVp. Wide variation in doses amongst different scanners suggests that standardisation of scanning protocols can reduce patient dose. New technological advances, such as dose-reduction software algorithms, can be adopted to reduce patient dose.

  10. Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

    SciTech Connect

    Chung, Eugene; Corbett, James R.; Moran, Jean M.; Griffith, Kent A.; Marsh, Robin B.; Feng, Mary; Jagsi, Reshma; Kessler, Marc L.; Ficaro, Edward C.; Pierce, Lori J.

    2013-03-15

    Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses to the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was −0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF.

  11. Maintenance eculizumab dose adjustment in the treatment of atypical hemolytic uremic syndrome: a case report and review of the literature.

    PubMed

    Thomson, Nick; Ulrickson, Matthew

    2016-08-01

    Atypical hemolytic uremic syndrome (aHUS) patients treated with eculizumab may require higher doses to achieve and maintain optimal clinical response. Further studies are warranted to elucidate optimal dosing regimens of eculizumab in aHUS patients, and whether dosing regimens can be predicted based on mutational status, eculizumab levels, or other testing. PMID:27525082

  12. Bladder dose-surface maps and urinary toxicity: Robustness with respect to motion in assessing local dose effects.

    PubMed

    Palorini, F; Botti, A; Carillo, V; Gianolini, S; Improta, I; Iotti, C; Rancati, T; Cozzarini, C; Fiorino, C

    2016-03-01

    The purpose of this study was to quantify the impact of inter-fraction modifications of bladder during RT of prostate cancer on bladder dose surface maps (DSM). Eighteen patients treated with daily image-guided Tomotherapy and moderate hypofractionation (70-72.8Gy at 2.5-2.6Gy/fr in 28 fractions and full bladder) were considered. Bladder contours were delineated on co-registered daily Megavoltage CT (MVCT) by a single observer and copied on the planning CT to generate dose-volume/surface histograms (DVH/DSH) and bladder DSMs. Discrepancies between planned and daily absorbed doses were analyzed through the average of individual systematic errors, the population systematic errors and the population random errors for the DVH/DSHs and DSMs. In total, 477 DVH/DSH and 472 DSM were available. DSH and DVH showed small population systematic errors of absolute surfaces (<3.4cm(2)) and volumes (<8.4cm(3)) at the highest doses. The dose to the posterior bladder base assessed on DSMs showed a mean systematic error below 1Gy, with population systematic and random errors within 4 and 3Gy, respectively. The region surrounding this area shows higher mean systematic errors (1-3Gy), population systematic (8-11Gy) and random (5-7Gy) errors. In conclusion, DVH/DSH and DSMs are quite stable with respect to inter-fraction variations in the high-dose region, within about 2cm from bladder base. Larger systematic variations occur in the anterior portion and cranially 2.5-3.5cm from the base. Results suggest that dose predictors related to the high dose area (including the trigone dose) are likely to be sufficiently reliable with respect to the expected variations due to variable bladder filling.

  13. A randomized controlled trial of increased dose and frequency of albendazole with standard dose DEC for treatment of Wuchereria bancrofti microfilaremics in Odisha, India.

    PubMed

    Kar, Shantanu Kumar; Dwibedi, Bhagirathi; Kerketa, Anna Salomi; Maharana, Antaryami; Panda, Sudanshu S; Mohanty, Prafulla Chandra; Horton, John; Ramachandran, Cherubala P

    2015-03-01

    Although current programmes to eliminate lymphatic filariasis have made significant progress it may be necessary to use different approaches to achieve the global goal, especially where compliance has been poor and 'hot spots' of continued infection exist. In the absence of alternative drugs, the use of higher or more frequent dosing with the existing drugs needs to be explored. We examined the effect of higher and/or more frequent dosing with albendazole with a fixed 300 mg dose of diethylcarbamazine in a Wuchereria bancrofti endemic area in Odisha, India. Following screening, 104 consenting adults were randomly assigned to treatment with the standard regimen annually for 24 months (S1), or annually with increased dose (800 mg albendazole)(H1) or with increased frequency (6 monthly) with either standard (S2) or increased (H2) dose. Pre-treatment microfilaria counts (GM) ranged from 348 to 459 mf/ml. Subjects were followed using microfilaria counts, OG4C3 antigen levels and ultrasound scanning for adult worm nests. Microfilarial counts tended to decrease more rapidly with higher or more frequent dosing at all time points. At 12 months, Mf clearance was marginally greater with the high dose regimens, while by 24 months, there was a trend to higher Mf clearance in the arm with increased frequency and 800 mg of albendazole (76.9%) compared to other arms, (S1:64%, S2:69.2% & H1:73.1%). Although higher and/or more frequent dosing showed a trend towards a greater decline in antigenemia and clearance of "nests", all regimens demonstrated the potential macrofilaricidal effect of the combination. The higher doses of albendazole did not result in a greater number or more severe side effects. The alternative regimens could be useful in the later stages of existing elimination programmes or achieving elimination more rapidly in areas where programmes have yet to start. PMID:25781977

  14. A Randomized Controlled Trial of Increased Dose and Frequency of Albendazole with Standard Dose DEC for Treatment of Wuchereria bancrofti Microfilaremics in Odisha, India

    PubMed Central

    Kerketa, Anna Salomi; Maharana, Antaryami; Panda, Sudanshu S; Mohanty, Prafulla Chandra; Horton, John; Ramachandran, Cherubala P

    2015-01-01

    Although current programmes to eliminate lymphatic filariasis have made significant progress it may be necessary to use different approaches to achieve the global goal, especially where compliance has been poor and ‘hot spots’ of continued infection exist. In the absence of alternative drugs, the use of higher or more frequent dosing with the existing drugs needs to be explored. We examined the effect of higher and/or more frequent dosing with albendazole with a fixed 300mg dose of diethylcarbamazine in a Wuchereria bancrofti endemic area in Odisha, India. Following screening, 104 consenting adults were randomly assigned to treatment with the standard regimen annually for 24 months (S1), or annually with increased dose (800mg albendazole)(H1) or with increased frequency (6 monthly) with either standard (S2) or increased (H2) dose. Pre-treatment microfilaria counts (GM) ranged from 348 to 459 mf/ml. Subjects were followed using microfilaria counts, OG4C3 antigen levels and ultrasound scanning for adult worm nests. Microfilarial counts tended to decrease more rapidly with higher or more frequent dosing at all time points. At 12 months, Mf clearance was marginally greater with the high dose regimens, while by 24 months, there was a trend to higher Mf clearance in the arm with increased frequency and 800mg of albendazole (76.9%) compared to other arms, (S1:64%, S2:69.2% & H1:73.1%). Although higher and/or more frequent dosing showed a trend towards a greater decline in antigenemia and clearance of “nests”, all regimens demonstrated the potential macrofilaricidal effect of the combination. The higher doses of albendazole did not result in a greater number or more severe side effects. The alternative regimens could be useful in the later stages of existing elimination programmes or achieving elimination more rapidly in areas where programmes have yet to start. PMID:25781977

  15. Investigation of dose-related effects of carnosine on anxiety with sympathetic skin response and T-maze.

    PubMed

    Dolu, Nazan; Acer, Hale; Kara, Ali Yucel

    2014-01-01

    Carnosine is a dipeptide formed of the amino acids β-alanine and histidine. Only a limited number of studies have examined the effects of carnosine on sympathetic nerve activation and anxiety. The present study was undertaken to determine the dose-related effects of carnosine on anxiety in the elevated T-maze test (ETM) with electrodermal activity (EDA). Carnosine was injected in three groups of rats with doses of 10 (low dose), 100 (medium dose) and 1000 (high dose) mg/kg i.p. Physiological saline was injected in the sham group. The anxiety scores of the rats were measured with ETM 20 minutes after injection. Then, SCL was measured. The decreased number of entries into the open arm (NEOA), the percentage of time spent in the open arm (% TSOA) and higher EDA [shown by skin conductance level (SCL)] indicate higher anxiety. The NEOA and % TSOA were lower in the high-dose group than in the other groups. SCL was lower in the medium-dose carnosine group than in the high-dose carnosine and sham groups. SCL was higher in the high-dose group than in the medium-dose and sham groups. Our results suggest that high-dose carnosine produced anxiety-like effects as assessed in the SCL and ETM. Medium-dose carnosine acted as an anxiolytic. The anxiety-related responses of carnosine depend on its dose-related effect. PMID:25649366

  16. Assessment of individual dose utilization vs. physician prescribing recommendations for recombinant activated factor VII (rFVIIa) in paediatric and adult patients with congenital haemophilia and alloantibody inhibitors (CHwI): the Dosing Observational Study in Hemophilia (DOSE).

    PubMed

    Gruppo, R A; Kessler, C M; Neufeld, E J; Cooper, D L

    2013-07-01

    Recent data from the Dosing Observational Study in Hemophilia diary study has described home treatment with recombinant activated factor VII (rFVIIa) in congenital haemophilia with inhibitors (CHwI). The current analysis compares prescribed and patient/caregiver-reported rFVIIa administration in paediatric and adult CHwI patients in this study. Patients with ≥ 4 bleeding episodes within a 3-month period prescribed rFVIIa as first-line therapy for bleeding episodes were eligible. Patients/caregivers completed a diary for ≥ 90 days or until the patient experienced four bleeds. Initial, total and mean rFVIIa doses reported for each bleeding episode were calculated and compared with the physician-prescribed doses. Of 52 enrolled patients (25 children; 27 adults), 39 (75%) completed the study. Children and adults had similar mean durations of bleeding episodes. Both patient groups were administered higher initial rFVIIa doses for joint bleeds than prescribed: median (range) 215.2 (74.1-400.0) mcg kg(-1) vs. 200.0 (61.0-270.0) mcg kg(-1) for children, and 231.3 (59.3-379.7) mcg kg(-1) vs. 123.0 (81.0-289.0) mcg kg(-1) for adults. The median infused dose for joint bleeds was higher in adults than children (175.2 vs. 148.0 mcg kg(-1) ), but children received significantly more doses per joint bleed than adults (median 6.5 vs. 3.0). The median total dose per joint bleed was higher in children than adults (1248.7 vs. 441.6). For children and adults, both initial and additional doses administered for bleeds were higher than prescribed. Children received higher total doses per bleed due to an increased number of infusions per bleed.

  17. WE-A-17A-12: The Influence of Eye Plaque Design On Dose Distributions and Dose- Volume Histograms

    SciTech Connect

    Aryal, P; Molloy, JA; Rivard, MJ

    2014-06-15

    Purpose: To investigate the effect of slot design of the model EP917 plaque on dose distributions and dose-volume histograms (DVHs). Methods: The dimensions and orientation of the slots in EP917 plaques were measured. In the MCNP5 radiation simulation geometry, dose distributions on orthogonal planes and DVHs for a tumor and sclera were generated for comparisons. 27 slot designs and 13 plaques were evaluated and compared with the published literature and the Plaque Simulator clinical treatment planning system. Results: The dosimetric effect of the gold backing composition and mass density was < 3%. Slot depth, width, and length changed the central axis (CAX) dose distributions by < 1% per 0.1 mm in design variation. Seed shifts in the slot towards the eye and shifts of the {sup 125} I-coated Ag rod within the capsule had the greatest impact on CAX dose distribution, increasing by 14%, 9%, 4%, and 2.5% at 1, 2, 5, and 10 mm, respectively, from the inner sclera. Along the CAX, dose from the full plaque geometry using the measured slot design was 3.4% ± 2.3% higher than the manufacturer-provided geometry. D{sub 10} for the simulated tumor, inner sclera, and outer sclera for the measured plaque was also higher, but 9%, 10%, and 20%, respectively. In comparison to the measured plaque design, a theoretical plaque having narrow and deep slots delivered 30%, 37%, and 62% lower D{sub 10} doses to the tumor, inner sclera, and outer sclera, respectively. CAX doses at −1, 0, 1, and 2 mm were also lower by a factor of 2.6, 1.4, 1.23, and 1.13, respectively. Conclusion: The study identified substantial sensitivity of the EP917 plaque dose distributions to slot design. However, it did not identify substantial dosimetric variations based on radionuclide choice ({sup 125}I, {sup 103}Pd, or {sup 131}Cs). COMS plaques provided lower scleral doses with similar tumor dose coverage.

  18. Peritoneal Dialysis Dose and Adequacy

    MedlinePlus

    ... Organizations​​ . (PDF, 345 KB)​​​​​ Alternate Language URL Peritoneal Dialysis Dose and Adequacy Page Content On this page: ... from the abdominal cavity. [ Top ] Types of Peritoneal Dialysis The two types of peritoneal dialysis differ mainly ...

  19. Energetic dose: Beyond fire and flint?

    USGS Publications Warehouse

    Linder, G.; Rattner, B.; Cohen, J.

    2000-01-01

    Nutritional and bioenergetic interactions influence exposure to environmental chemicals and may affect the risk realized when wildlife are exposed in the field. Here, food-chain analysis focuses on prairie voles (Microtus ochrogaster) and the evaluation of chemical risks associated with paraquat following 10-d dietary exposures. Reproductive effects were measured in 60-d trials that followed exposures to paraquat-tainted feed: control (untainted feed); 21 mg paraquat/kg feed; 63 mg paraquat/kg feed; and feed-restricted control (untainted feed restricted to 60% baseline consumption). Reproductive success was evaluated in control and treated breeding pairs, and a preliminary bioenergetics analysis was completed in parallel to derive exposure dose. Although reproductive performance differed among groups, feed-restriction appeared to be the dominant treatment effect observed in these 10-d feeding exposure/limited reproductive trials. Exposure dose ranged from 3.70-3.76 to 9.41-11.51 mg parquat/kg BW/day at 21 and 63 mg paraquat/kg feed stock exposures, respectively. Energetic doses as ug paraquat/kcal yielded preliminary estimates of energetic costs associated with paraquat exposure, and were similar within treatments for both sexes, ranging from 4.2-5.5 and 13.1-15.0 ug paraquat/kcal for voles exposed to 21 mg/kg feed stock and 63 mg/kg feed stock, respectively. Given the increasing likelihood that environmental chemicals will be found in wildlife habitat at 'acceptable levels', the critical role that wildlife nutrition plays in evaluating ecological risks should be fully integrated into the assessment process. Tools applied to the analysis of risk must gain higher resolution than the relatively crude methods we currently bring to the process.

  20. Higher: Setting a Higher Bar for Higher Ed. 2013 Annual Report

    ERIC Educational Resources Information Center

    American Council of Trustees and Alumni, 2014

    2014-01-01

    The American Council of Trustees and Alumni (ACTA) is leading the charge to return "higher" to higher education. We are challenging the status quo to restore academic freedom, academic rigor, and real accountability to higher education. And, we are doing so with an ever-widening network of supporters and partners.

  1. A simplified technique for delivering total body irradiation (TBI) with improved dose homogeneity

    SciTech Connect

    Yao Rui; Bernard, Damian; Turian, Julius; Abrams, Ross A.; Sensakovic, William; Fung, Henry C.; Chu, James C. H.

    2012-04-15

    Purpose: Total body irradiation (TBI) with megavoltage photon beams has been accepted as an important component of management for a number of hematologic malignancies, generally as part of bone marrow conditioning regimens. The purpose of this paper is to present and discuss the authors' TBI technique, which both simplifies the treatment process and improves the treatment quality. Methods: An AP/PA TBI treatment technique to produce uniform dose distributions using sequential collimator reductions during each fraction was implemented, and a sample calculation worksheet is presented. Using this methodology, the dosimetric characteristics of both 6 and 18 MV photon beams, including lung dose under cerrobend blocks was investigated. A method of estimating midplane lung doses based on measured entrance and exit doses was proposed, and the estimated results were compared with measurements. Results: Whole body midplane dose uniformity of {+-}10% was achieved with no more than two collimator-based beam modulations. The proposed model predicted midplane lung doses 5% to 10% higher than the measured doses for 6 and 18 MV beams. The estimated total midplane doses were within {+-}5% of the prescribed midplane dose on average except for the lungs where the doses were 6% to 10% lower than the prescribed dose on average. Conclusions: The proposed TBI technique can achieve dose uniformity within {+-}10%. This technique is easy to implement and does not require complicated dosimetry and/or compensators.

  2. Pediatric organ dose measurements in axial and helical multislice CT

    SciTech Connect

    McDermott, Alanna; White, R. Allen; Mc-Nitt-Gray, Mike; Angel, Erin; Cody, Dianna

    2009-05-15

    An anthropomorphic pediatric phantom (5-yr-old equivalent) was used to determine organ doses at specific surface and internal locations resulting from computed tomography (CT) scans. This phantom contains four different tissue-equivalent materials: Soft tissue, bone, brain, and lung. It was imaged on a 64-channel CT scanner with three head protocols (one contiguous axial scan and two helical scans [pitch=0.516 and 0.984]) and four chest protocols (one contiguous axial scan and three helical scans [pitch=0.516, 0.984, and 1.375]). Effective mA s [=(tube currentxrotation time)/pitch] was kept nearly constant at 200 effective mA s for head and 290 effective mA s for chest protocols. Dose measurements were acquired using thermoluminescent dosimeter powder in capsules placed at locations internal to the phantom and on the phantom surface. The organs of interest were the brain, both eyes, thyroid, sternum, both breasts, and both lungs. The organ dose measurements from helical scans were lower than for contiguous axial scans by 0% to 25% even after adjusting for equivalent effective mA s. There was no significant difference (p>0.05) in organ dose values between the 0.516 and 0.984 pitch values for both head and chest scans. The chest organ dose measurements obtained at a pitch of 1.375 were significantly higher than the dose values obtained at the other helical pitches used for chest scans (p<0.05). This difference was attributed to the automatic selection of the large focal spot due to a higher tube current value. These findings suggest that there may be a previously unsuspected radiation dose benefit associated with the use of helical scan mode during computed tomography scanning.

  3. Verification of Internal Dose Calculations.

    NASA Astrophysics Data System (ADS)

    Aissi, Abdelmadjid

    The MIRD internal dose calculations have been in use for more than 15 years, but their accuracy has always been questionable. There have been attempts to verify these calculations; however, these attempts had various shortcomings which kept the question of verification of the MIRD data still unanswered. The purpose of this research was to develop techniques and methods to verify the MIRD calculations in a more systematic and scientific manner. The research consisted of improving a volumetric dosimeter, developing molding techniques, and adapting the Monte Carlo computer code ALGAM to the experimental conditions and vice versa. The organic dosimetric system contained TLD-100 powder and could be shaped to represent human organs. The dosimeter possessed excellent characteristics for the measurement of internal absorbed doses, even in the case of the lungs. The molding techniques are inexpensive and were used in the fabrication of dosimetric and radioactive source organs. The adaptation of the computer program provided useful theoretical data with which the experimental measurements were compared. The experimental data and the theoretical calculations were compared for 6 source organ-7 target organ configurations. The results of the comparison indicated the existence of an agreement between measured and calculated absorbed doses, when taking into consideration the average uncertainty (16%) of the measurements, and the average coefficient of variation (10%) of the Monte Carlo calculations. However, analysis of the data gave also an indication that the Monte Carlo method might overestimate the internal absorbed doses. Even if the overestimate exists, at least it could be said that the use of the MIRD method in internal dosimetry was shown to lead to no unnecessary exposure to radiation that could be caused by underestimating the absorbed dose. The experimental and the theoretical data were also used to test the validity of the Reciprocity Theorem for heterogeneous

  4. SU-E-T-313: The Accuracy of the Acuros XB Advanced Dose Calculation Algorithm for IMRT Dose Distributions in Head and Neck

    SciTech Connect

    Araki, F; Onizuka, R; Ohno, T; Tomiyama, Y; Hioki, K

    2014-06-01

    Purpose: To investigate the accuracy of the Acuros XB version 11 (AXB11) advanced dose calculation algorithm by comparing with Monte Caro (MC) calculations. The comparisons were performed with dose distributions for a virtual inhomogeneity phantom and intensity-modulated radiotherapy (IMRT) in head and neck. Methods: Recently, AXB based on Linear Boltzmann Transport Equation has been installed in the Eclipse treatment planning system (Varian Medical Oncology System, USA). The dose calculation accuracy of AXB11 was tested by the EGSnrc-MC calculations. In additions, AXB version 10 (AXB10) and Analytical Anisotropic Algorithm (AAA) were also used. First the accuracy of an inhomogeneity correction for AXB and AAA algorithms was evaluated by comparing with MC-calculated dose distributions for a virtual inhomogeneity phantom that includes water, bone, air, adipose, muscle, and aluminum. Next the IMRT dose distributions for head and neck were compared with the AXB and AAA algorithms and MC by means of dose volume histograms and three dimensional gamma analysis for each structure (CTV, OAR, etc.). Results: For dose distributions with the virtual inhomogeneity phantom, AXB was in good agreement with those of MC, except the dose in air region. The dose in air region decreased in order of MCdose kernel of water, the doses in regions for air, bone, and aluminum considerably became higher than those of AXB and MC. The pass rates of the gamma analysis for IMRT dose distributions in head and neck were similar to those of MC in order of AXB11dose calculation accuracy of AXB11 was almost equivalent to the MC dose calculation.

  5. NIRS external dose estimation system for Fukushima residents after the Fukushima Dai-ichi NPP accident

    NASA Astrophysics Data System (ADS)

    Akahane, Keiichi; Yonai, Shunsuke; Fukuda, Shigekazu; Miyahara, Nobuyuki; Yasuda, Hiroshi; Iwaoka, Kazuki; Matsumoto, Masaki; Fukumura, Akifumi; Akashi, Makoto

    2013-04-01

    The great east Japan earthquake and subsequent tsunamis caused Fukushima Dai-ichi Nuclear Power Plant (NPP) accident. National Institute of Radiological Sciences (NIRS) developed the external dose estimation system for Fukushima residents. The system is being used in the Fukushima health management survey. The doses can be obtained by superimposing the behavior data of the residents on the dose rate maps. For grasping the doses, 18 evacuation patterns of the residents were assumed by considering the actual evacuation information before using the survey data. The doses of the residents from the deliberate evacuation area were relatively higher than those from the area within 20 km radius. The estimated doses varied from around 1 to 6 mSv for the residents evacuated from the representative places in the deliberate evacuation area. The maximum dose in 18 evacuation patterns was estimated to be 19 mSv.

  6. NIRS external dose estimation system for Fukushima residents after the Fukushima Dai-ichi NPP accident.

    PubMed

    Akahane, Keiichi; Yonai, Shunsuke; Fukuda, Shigekazu; Miyahara, Nobuyuki; Yasuda, Hiroshi; Iwaoka, Kazuki; Matsumoto, Masaki; Fukumura, Akifumi; Akashi, Makoto

    2013-01-01

    The great east Japan earthquake and subsequent tsunamis caused Fukushima Dai-ichi Nuclear Power Plant (NPP) accident. National Institute of Radiological Sciences (NIRS) developed the external dose estimation system for Fukushima residents. The system is being used in the Fukushima health management survey. The doses can be obtained by superimposing the behavior data of the residents on the dose rate maps. For grasping the doses, 18 evacuation patterns of the residents were assumed by considering the actual evacuation information before using the survey data. The doses of the residents from the deliberate evacuation area were relatively higher than those from the area within 20 km radius. The estimated doses varied from around 1 to 6 mSv for the residents evacuated from the representative places in the deliberate evacuation area. The maximum dose in 18 evacuation patterns was estimated to be 19 mSv.

  7. Evaluation of radiation dose to neonates in a special care baby unit

    NASA Astrophysics Data System (ADS)

    Alzimami, K.; Sulieman, A.; Yousif, A.; Babikir, E.; Salih, I.

    2014-11-01

    The purpose of this study was to evaluate the patient entrance surface dose (ESD), organ dose and effective dose for neonates in the special care baby unit (SCBU) up to 28 days after birth. A total of 135 patients were examined during 4 months. ESDs were calculated from patient exposure parameters using DosCal software. Effective doses were calculated using software from the National Radiological Protection Board (NRPB). The mean patient ESD per procedure was 80±0.02 μGy. The mean and range of the effective dose per procedure were 0.02 (0.01-0.3) mSv. The radiation dose in this study was higher compared to previous studies. A dedicated X-ray machine with additional filtration is recommended for patient dose reductions.

  8. Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure

    PubMed Central

    Johnston, Sara C.; Lin, Kenny L.; Twenhafel, Nancy A.; Raymond, Jo Lynne W.; Shamblin, Joshua D.; Wollen, Suzanne E.; Wlazlowski, Carly B.; Wilkinson, Eric R.; Botto, Miriam A.; Goff, Arthur J.

    2015-01-01

    Marburg virus infection in humans causes a hemorrhagic disease with a high case fatality rate. Countermeasure development requires the use of well-characterized animal models that mimic human disease. To further characterize the cynomolgus macaque model of MARV/Angola, two independent dose response studies were performed using the intramuscular or aerosol routes of exposure. All animals succumbed at the lowest target dose; therefore, a dose effect could not be determined. For intramuscular-exposed animals, 100 PFU was the first target dose that was not significantly different than higher target doses in terms of time to disposition, clinical pathology, and histopathology. Although a significant difference was not observed between aerosol-exposed animals in the 10 PFU and 100 PFU target dose groups, 100 PFU was determined to be the lowest target dose that could be consistently obtained and accurately titrated in aerosol studies. PMID:26413900

  9. Alabama Commission on Higher Education. Occasional Papers on Higher Education.

    ERIC Educational Resources Information Center

    Alabama State Commission on Higher Education, Montgomery.

    Two papers on the funding formula of the Alabama Commission for Higher Education are presented. The first paper, by John F. Porter, Jr., "The Origins and Evolutions of the Funding Formula Model Utilized by the Alabama Commission on Higher Education, 1973-82," presents the historical antecedents for the existing formula elements and notes…

  10. On higher holonomy invariants in higher gauge theory I

    NASA Astrophysics Data System (ADS)

    Zucchini, Roberto

    2016-05-01

    This is the first of a series of two technical papers devoted to the analysis of holonomy invariants in strict higher gauge theory with end applications in higher Chern-Simons theory. For a flat 2-connection, we define the 2-holonomy of surface knots of arbitrary genus and determine its covariance properties under 1-gauge transformation and change of base data.

  11. Prediction of 10-fold coordinated TiO2 and SiO2 structures at multimegabar pressures

    PubMed Central

    Lyle, Matthew J.; Pickard, Chris J.; Needs, Richard J.

    2015-01-01

    We predict by first-principles methods a phase transition in TiO2 at 6.5 Mbar from the Fe2P-type polymorph to a ten-coordinated structure with space group I4/mmm. This is the first report, to our knowledge, of the pressure-induced phase transition to the I4/mmm structure among all dioxide compounds. The I4/mmm structure was found to be up to 3.3% denser across all pressures investigated. Significant differences were found in the electronic properties of the two structures, and the metallization of TiO2 was calculated to occur concomitantly with the phase transition to I4/mmm. The implications of our findings were extended to SiO2, and an analogous Fe2P-type to I4/mmm transition was found to occur at 10 TPa. This is consistent with the lower-pressure phase transitions of TiO2, which are well-established models for the phase transitions in other AX2 compounds, including SiO2. As in TiO2, the transition to I4/mmm corresponds to the metallization of SiO2. This transformation is in the pressure range reached in the interiors of recently discovered extrasolar planets and calls for a reformulation of the equations of state used to model them. PMID:25991859

  12. Prediction of 10-fold coordinated TiO2 and SiO2 structures at multimegabar pressures.

    PubMed

    Lyle, Matthew J; Pickard, Chris J; Needs, Richard J

    2015-06-01

    We predict by first-principles methods a phase transition in TiO2 at 6.5 Mbar from the Fe2P-type polymorph to a ten-coordinated structure with space group I4/mmm. This is the first report, to our knowledge, of the pressure-induced phase transition to the I4/mmm structure among all dioxide compounds. The I4/mmm structure was found to be up to 3.3% denser across all pressures investigated. Significant differences were found in the electronic properties of the two structures, and the metallization of TiO2 was calculated to occur concomitantly with the phase transition to I4/mmm. The implications of our findings were extended to SiO2, and an analogous Fe2P-type to I4/mmm transition was found to occur at 10 TPa. This is consistent with the lower-pressure phase transitions of TiO2, which are well-established models for the phase transitions in other AX2 compounds, including SiO2. As in TiO2, the transition to I4/mmm corresponds to the metallization of SiO2. This transformation is in the pressure range reached in the interiors of recently discovered extrasolar planets and calls for a reformulation of the equations of state used to model them. PMID:25991859

  13. 13 Years of TOPEX/POSEIDON Precision Orbit Determination and the 10-fold Improvement in Expected Orbit Accuracy

    NASA Technical Reports Server (NTRS)

    Lemoine, F. G.; Zelensky, N. P.; Luthcke, S. B.; Rowlands, D. D.; Beckley, B. D.; Klosko, S. M.

    2006-01-01

    Launched in the summer of 1992, TOPEX/POSEIDON (T/P) was a joint mission between NASA and the Centre National d Etudes Spatiales (CNES), the French Space Agency, to make precise radar altimeter measurements of the ocean surface. After the remarkably successful 13-years of mapping the ocean surface T/P lost its ability to maneuver and was de-commissioned January 2006. T/P revolutionized the study of the Earth s oceans by vastly exceeding pre-launch estimates of surface height accuracy recoverable from radar altimeter measurements. The precision orbit lies at the heart of the altimeter measurement providing the reference frame from which the radar altimeter measurements are made. The expected quality of orbit knowledge had limited the measurement accuracy expectations of past altimeter missions, and still remains a major component in the error budget of all altimeter missions. This paper describes critical improvements made to the T/P orbit time series over the 13-years of precise orbit determination (POD) provided by the GSFC Space Geodesy Laboratory. The POD improvements from the pre-launch T/P expectation of radial orbit accuracy and Mission requirement of 13-cm to an expected accuracy of about 1.5-cm with today s latest orbits will be discussed. The latest orbits with 1.5 cm RMS radial accuracy represent a significant improvement to the 2.0-cm accuracy orbits currently available on the T/P Geophysical Data Record (GDR) altimeter product.

  14. Reagents for astatination of biomolecules. 6. An intact antibody conjugated with a maleimido-closo-decaborate(2-) reagent via sulfhydryl groups had considerably higher kidney concentrations than the same antibody conjugated with an isothiocyanato-closo-decaborate(2-) reagent via lysine amines.

    PubMed

    Wilbur, D Scott; Chyan, Ming-Kuan; Nakamae, Hirohisa; Chen, Yun; Hamlin, Donald K; Santos, Erlinda B; Kornblit, Brian T; Sandmaier, Brenda M

    2012-03-21

    We are investigating the use of an (211)At-labeled anti-CD45 monoclonal antibody (mAb) as a replacement of total body irradiation in conditioning regimens designed to decrease the toxicity of hematopoietic cell transplantation (HCT). As part of that investigation, dose-escalation studies were conducted in dogs using (211)At-labeled anticanine CD45 mAb, CA12.10C12, conjugated with a maleimido-closo-decaborate(2-) derivative, 4. Unacceptable renal toxicity was noted in the dogs receiving doses in the 0.27-0.62 mCi/kg range. This result was not anticipated, as no toxicity had been noted in prior biodistribution and toxicity studies conducted in mice. Studies were conducted to understand the cause of the renal toxicity and to find a way to circumvent it. A dog biodistribution study was conducted with (123)I-labeled CA12.10C12 that had been conjugated with 4. The biodistribution data showed that 10-fold higher kidney concentrations were obtained with the maleimido-conjugate than had been obtained in a previous biodistribution study with (123)I-labeled CA12.10C12 conjugated with an amine-reactive phenylisothiocyanato-CHX-A″ derivative. The difference in kidney concentrations observed in dogs for the two conjugation approaches led to an investigation of the reagents. SE-HPLC analyses showed that the purity of the CA12.10C12 conjugated via reduced disulfides was lower than that obtained with amine-reactive conjugation reagents, and nonreducing SDS-PAGE analyses indicated protein fragments were present in the disulfide reduced conjugate. Although we had previously prepared closo-decaborate(2-) derivatives with amine-reactive functional groups (e.g., 6 and 8), a new, easily synthesized, amine-reactive (phenylisothiocyanate) derivative, 10, was prepared for use in the current studies. A biodistribution was conducted with coadministered (125)I- and (211)At-labeled CA12.10C10 conjugated with 10. In that study, lower kidney concentrations were obtained for both radionuclides

  15. Reagents for astatination of biomolecules. 6. An intact antibody conjugated with a maleimido-closo-decaborate(2-) reagent via sulfhydryl groups had considerably higher kidney concentrations than the same antibody conjugated with an isothiocyanato-closo-decaborate(2-) reagent via lysine amines.

    PubMed

    Wilbur, D Scott; Chyan, Ming-Kuan; Nakamae, Hirohisa; Chen, Yun; Hamlin, Donald K; Santos, Erlinda B; Kornblit, Brian T; Sandmaier, Brenda M

    2012-03-21

    We are investigating the use of an (211)At-labeled anti-CD45 monoclonal antibody (mAb) as a replacement of total body irradiation in conditioning regimens designed to decrease the toxicity of hematopoietic cell transplantation (HCT). As part of that investigation, dose-escalation studies were conducted in dogs using (211)At-labeled anticanine CD45 mAb, CA12.10C12, conjugated with a maleimido-closo-decaborate(2-) derivative, 4. Unacceptable renal toxicity was noted in the dogs receiving doses in the 0.27-0.62 mCi/kg range. This result was not anticipated, as no toxicity had been noted in prior biodistribution and toxicity studies conducted in mice. Studies were conducted to understand the cause of the renal toxicity and to find a way to circumvent it. A dog biodistribution study was conducted with (123)I-labeled CA12.10C12 that had been conjugated with 4. The biodistribution data showed that 10-fold higher kidney concentrations were obtained with the maleimido-conjugate than had been obtained in a previous biodistribution study with (123)I-labeled CA12.10C12 conjugated with an amine-reactive phenylisothiocyanato-CHX-A″ derivative. The difference in kidney concentrations observed in dogs for the two conjugation approaches led to an investigation of the reagents. SE-HPLC analyses showed that the purity of the CA12.10C12 conjugated via reduced disulfides was lower than that obtained with amine-reactive conjugation reagents, and nonreducing SDS-PAGE analyses indicated protein fragments were present in the disulfide reduced conjugate. Although we had previously prepared closo-decaborate(2-) derivatives with amine-reactive functional groups (e.g., 6 and 8), a new, easily synthesized, amine-reactive (phenylisothiocyanate) derivative, 10, was prepared for use in the current studies. A biodistribution was conducted with coadministered (125)I- and (211)At-labeled CA12.10C10 conjugated with 10. In that study, lower kidney concentrations were obtained for both radionuclides

  16. Reagents for astatination of biomolecules. 6. An intact antibody conjugated with a maleimido-closo-decaborate(2-) reagent via sulfhydryl groups had considerably higher kidney concentrations than the same antibody conjugated with an isothiocyanato-closo-decaborate(2-) reagent via lysine amines

    PubMed Central

    Wilbur, D. Scott; Chyan, Ming-Kuan; Nakamae, Hirohisa; Chen, Yun; Hamlin, Donald K.; Santos, Erlinda B.; Kornblit, Brian T.; Sandmaier, Brenda M.

    2012-01-01

    We are investigating the use of an 211At-labeled anti-CD45 monoclonal antibody (mAb) as a replacement of total body irradiation in conditioning regimens designed to decrease the toxicity of hematopoietic cell transplantation (HCT). As part of that investigation, dose-escalation studies were conducted in dogs using 211At-labeled anti-canine CD45 mAb, CA12.10C12, conjugated with a maleimido-closo-decaborate(2-) derivative, 4. Unacceptable renal toxicity was noted in the dogs receiving doses in the 0.27 – 0.62 mCi/kg range. This result was not anticipated, as no toxicity had been noted in prior biodistribution and toxicity studies conducted in mice. Studies were conducted to understand the cause of the renal toxicity and to find a way to circumvent it. A dog biodistribution study was conducted with 123Ilabeled CA12.10C12 that had been conjugated with 4. The biodistribution data showed that 10-fold higher kidney concentrations were obtained with the maleimido-conjugate than had been obtained in a previous biodistribution study with 123I-labeled CA12.10C12 conjugated with an amine-reactive phenylisothiocyanato-CHX-A” derivative. The difference in kidney concentrations observed in dogs for the two conjugation approaches led to an investigation of the reagents. SE-HPLC analyses showed that the purity of the CA12.10C12 conjugated via reduced disulfides was lower than that obtained with amine-reactive conjugation reagents, and non-reducing SDS-PAGE analyses indicated protein fragments were present in the disulfide reduced conjugate. Although we had previously prepared closo-decaborate(2-) derivatives with amine-reactive functional groups (e.g. 6 & 8), a new easily synthesized, amine-reactive (phenylisothiocyanate) derivative, 10, was prepared for use in the current studies. A biodistribution was conducted with co-administered 125I- and 211At-labeled CA12.10C10 conjugated with 10. In that study, lower kidney concentrations were obtained for both radionuclides than had

  17. [Epilepsy with higher brain dysfunction].

    PubMed

    Sugimoto, Azusa; Midorikawa, Akira; Koyama, Shinichi; Futamura, Akinori; Kuroda, Takeshi; Fujita, Kazuhisa; Itaya, Kazuhiro; Ishigaki, Seiichiro; Kawamura, Mitsuru

    2013-02-01

    Acquired higher brain dysfunction is for the most part due to cerebral vascular disease, but epilepsy may also be a cause. In this study with five patients, we discuss the advantages of anti-epileptic drugs (AEDs) for persistent higher brain dysfunction. The patients showed chronic amnesia or acute aphasia, with associated symptoms like personality change. All five cases affected automatism or convulsive attack, though only after the emergence of higher brain dysfunction and administration of AEDs. There were underlying diseases like cerebral arteriovenous malformation in four cases, but the other patient had none. Electroencephalogram and single photon emission computed tomography revealed one case of aphasia epilepsy with higher brain dysfunction. These results suggest the potential therapeutic efficacy of AEDs for persistent higher brain dysfunction, and we must differentiate epilepsy with higher brain dysfunction from dementia or cerebral vascular disease. PMID:23399676

  18. Busulfan dosing in children with BMIs ≥ 85% undergoing HSCT: a new optimal strategy.

    PubMed

    Browning, Brittan; Thormann, Kimberly; Donaldson, Amy; Halverson, Terri; Shinkle, Marie; Kletzel, Morris

    2011-09-01

    Childhood obesity has more than tripled in the past 30 years. The prevalence of overweight and obese children has also increased in the pediatric cancer setting, causing substantial concern over proper chemotherapeutic dosing in this population. The purpose of this study was to determine if children with an increased body mass index (BMI) have an alteration in busulfan pharmacokinetics during hematopoietic stem cell transplant (HSCT) conditioning. We retrospectively reviewed data on busulfan pharmacokinetics (PK) on HSCT subjects (subjects were part of a prospective study previously reported by our group at Children's Memorial Hospital) to determine appropriateness of dosing. Subjects were divided into appropriate BMI categories (<25th percentile, 25th-85th percentile, ≥ 85th percentile) and busulfan PK dosing was analyzed (test dose, regimen dose, area under the curve [AUC], and clearance). The dosing based on PK test dose data of children with BMI ≥ 85% was compared against the package insert dosing recommendations of using adjusted ideal body weight (AIBW) in obese patients to determine which dosing schema was most accurate. Children with high BMIs had higher AUCs when dosing on actual weight then their normal or low BMI counterparts. This indicates that children with a high BMI require less drug (2.9 mg/kg using actual body weight) to achieve the same AUC as children with normal BMI (4.0 mg/kg) or low BMI (3.6 mg/kg). Using the recommended AIBW dosing schema, 53% of the patients with high BMIs would have had regimen dose AUCs ≥ 20% over/under the target; whereas with the PK test dose method, only 16% of the patients with high BMIs had regimen dose AUCs ≥ 20% over/under the target. PK testing continues to be the gold standard for busulfan dosing in children. Particular vigilance should be paid to PK monitoring in high BMI categories because of the potential risk of imprecise dosing when using the AIBW schema.

  19. 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.

  20. Justification of permissible doses of radiation during prolonged space flights

    NASA Technical Reports Server (NTRS)

    Grigoryev, Y. G.; Abel, K.; Varteres, V.; Nilolov, N.; Karpfel, Z.; Prislichka, M.

    1974-01-01

    Maximum permissible radiation doses for astronauts are reported based on chronic radiation experiments with dogs and actual measurements during space flights. Observed were clinical conditions, peripheral blood and marrow, the state of the cardiovascular system, higher nervous activity, the state of the vestibular analyzer, the organ of vision, spermatogenic function and the ability to reproduce, the state of immunity and a number of biological indices in blood and tissues. The following maximum permissible doses are determined as preliminary values: 1 year of flight - 200 rem; 2 years of flight - 250 rem; 3 years of flight - 275 rem.

  1. Life span of C57 mice as influenced by radiation dose, dose rate, and age at exposure

    SciTech Connect

    Spalding, J.F.; Thomas, R.G.; Tietjen, G.L.

    1982-10-01

    This study was designed to measure the life shortening of C57BL/6J male mice as a result of exposure to five external doses from /sup 60/Co gamma radiation delivered at six different dose rates. Total doses ranged from 20 to 1620 rad at exposure rates ranging from 0.7 to 36,000 R/day. The ages of the mice at exposure were newborn, 2, 6, or 15 months. Two replications were completed. Although death was the primary endpoint, we did perform gross necropsies. The life span findings are variable, but we found no consistent shortening compared to control life spans. Therefore, we cannot logically extrapolate life shortening to lower doses, from the data we have obtained. In general, the younger the animals were at the beginning of exposure, the longer their life spans were compared to those of controls. This relationship weakened at the higher doses and dose rates, as mice in these categories tended not to have significantly different life spans from controls. Using life span as a criterion, we find this study suggests that some threshold dosage may exist beyond which effects of external irradiation may be manifested. Up to this threshold, there is no shortening effect on life span compared to that of control mice. Our results are in general agreement with the results of other researchers investigating human and other animal life span effects on irradiation.

  2. The cytokinesis-blocked micronucleus assay: dose-response calibration curve, background frequency in the population and dose estimation.

    PubMed

    Rastkhah, E; Zakeri, F; Ghoranneviss, M; Rajabpour, M R; Farshidpour, M R; Mianji, F; Bayat, M

    2016-03-01

    An in vitro study of the dose responses of human peripheral blood lymphocytes was conducted with the aim of creating calibrated dose-response curves for biodosimetry measuring up to 4 Gy (0.25-4 Gy) of gamma radiation. The cytokinesis-blocked micronucleus (CBMN) assay was employed to obtain the frequencies of micronuclei (MN) per binucleated cell in blood samples from 16 healthy donors (eight males and eight females) in two age ranges of 20-34 and 35-50 years. The data were used to construct the calibration curves for men and women in two age groups, separately. An increase in micronuclei yield with the dose in a linear-quadratic way was observed in all groups. To verify the applicability of the constructed calibration curve, MN yields were measured in peripheral blood lymphocytes of two real overexposed subjects and three irradiated samples with unknown dose, and the results were compared with dose values obtained from measuring dicentric chromosomes. The comparison of the results obtained by the two techniques indicated a good agreement between dose estimates. The average baseline frequency of MN for the 130 healthy non-exposed donors (77 men and 55 women, 20-60 years old divided into four age groups) ranged from 6 to 21 micronuclei per 1000 binucleated cells. Baseline MN frequencies were higher for women and for the older age group. The results presented in this study point out that the CBMN assay is a reliable, easier and valuable alternative method for biological dosimetry.

  3. Chromosome aberrations in human lymphocytes induced by 250 MeV protons: effects of dose, dose rate and shielding

    NASA Technical Reports Server (NTRS)

    George, K.; Willingham, V.; Wu, H.; Gridley, D.; Nelson, G.; Cucinotta, F. A.

    2002-01-01

    Although the space radiation environment consists predominantly of energetic protons, astronauts inside a spacecraft are chronically exposed to both primary particles as well as secondary particles that are generated when the primary particles penetrate the spacecraft shielding. Secondary neutrons and secondary charged particles can have an LET value that is greater than the primary protons and, therefore, produce a higher relative biological effectiveness (RBE). Using the accelerator facility at Loma Linda University, we exposed human lymphocytes in vitro to 250 MeV protons with doses ranging from 0 to 60 cGy at three different dose rates: a low dose rate of 7.5 cGy/h, an intermediate dose rate of 30 cGy/h and a high dose rate of 70 cGy/min. The effect of 15 g/cm2 aluminum shielding on the induction of chromosome aberrations was investigated for each dose rate. After exposure, lymphocytes were incubated in growth medium containing phytohemagglutinin (PHA) and chromosome spreads were collected using a chemical-induced premature chromosome condensation (PCC) technique. Aberrations were analyzed using the fluorescence in situ hybridization (FISH) technique with three different colored chromosome-painting probes. The frequency of reciprocal and complex-type chromosome exchanges were compared in shielded and unshielded samples. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

  4. Improving Low-Dose Blood-Brain Barrier Permeability Quantification Using Sparse High-Dose Induced Prior for Patlak Model

    PubMed Central

    Fang, Ruogu; Karlsson, Kolbeinn; Chen, Tsuhan; Sanelli, Pina C.

    2014-01-01

    Blood-brain-barrier permeability (BBBP) measurements extracted from the perfusion computed tomography (PCT) using the Patlak model can be a valuable indicator to predict hemorrhagic transformation in patients with acute stroke. Unfortunately, the standard Patlak model based PCT requires excessive radiation exposure, which raised attention on radiation safety. Minimizing radiation dose is of high value in clinical practice but can degrade the image quality due to the introduced severe noise. The purpose of this work is to construct high quality BBBP maps from low-dose PCT data by using the brain structural similarity between different individuals and the relations between the high- and low-dose maps. The proposed sparse high-dose induced (shd-Patlak) model performs by building a high-dose induced prior for the Patlak model with a set of location adaptive dictionaries, followed by an optimized estimation of BBBP map with the prior regularized Patlak model. Evaluation with the simulated low-dose clinical brain PCT datasets clearly demonstrate that the shd-Patlak model can achieve more significant gains than the standard Patlak model with improved visual quality, higher fidelity to the gold standard and more accurate details for clinical analysis. PMID:24200529

  5. Effects of acute low doses of gamma-radiation on erythrocytes membrane.

    PubMed

    Mahmoud, Sherif S; El-Sakhawy, Eman; Abdel-Fatah, Eman S; Kelany, Adel M; Rizk, Rizk M

    2011-03-01

    It is believed that any dose of ionizing radiation may damage cells and that the mutated cells could develop into cancer cells. Additionally, results of research performed over the past century on the effects of low doses of ionizing radiation on biological organisms show beneficial health effects, called hormesis. Much less is known about the cellular response to low doses of ionizing radiation, such as those typical for medical diagnostic procedures, normal occupational exposures or cosmic-ray exposures at flight altitudes. Extrapolating from the effects observed at higher doses to predict changes in cells after low-dose exposure is problematic. We examined the biological effects of low doses (0.01-0.3 Gy) of γ-radiation on the membrane characteristics of erythrocytes of albino rats and carried out osmotic fragility tests and Fourier transform infrared spectroscopy (FTIR). Our results indicate that the lowest three doses in the investigated radiation range, i.e., 0.01, 0.025 and 0.05 Gy, resulted in positive effects on the erythrocyte membranes, while a dose of 0.1 Gy appeared to represent the limiting threshold dose of those positive effects. Doses higher than 0.1 Gy were associated with the denaturation of erythrocyte proteins. PMID:20865271

  6. Methotrexate Dosing Regimen for Plaque-type Psoriasis: A Systematic Review of the Use of Test-dose, Start-dose, Dosing Scheme, Dose Adjustments, Maximum Dose and Folic Acid Supplementation.

    PubMed

    Menting, Stef P; Dekker, Paul M; Limpens, Jacqueline; Hooft, Lotty; Spuls, Phyllis I

    2016-01-01

    There is a range of methotrexate dosing regimens for psoriasis. This review summarizes the evidence for test-dose, start-dose, dosing scheme, dose adjustments, maximum dose and use of folic acid. A literature search for randomized controlled trials and guidelines was performed. Twenty-three randomized controlled trials (29 treatment groups) and 10 guidelines were included. Two treatment groups used a test-dose, 5 guidelines recommend it. The methotrexate start-dose in randomized controlled trials varied from 5 to 25 mg/week, most commonly being either 7.5 mg or 15 mg. Guidelines vary from 5 to 15 mg/week. Methotrexate was administered as a single dose or in a Weinstein schedule in 15 and 11 treatment-groups, respectively; both recommended equally in guidelines. A fixed dose (n = 18), predefined dose (n = 3), or dose adjusted on clinical improvement (n = 8) was used, the last also being recommended in guidelines. Ten treatment groups used folic acid; in 2 it was allowed, in 14 not mentioned, and in 3 no folic acid was used. Most guidelines recommend the use of folic acid. Authors' suggestions for methotrexate dosing are given.

  7. Pharmacokinetics of zidovudine dosed twice daily according to World Health Organization weight bands in Ugandan HIV-infected children.

    PubMed

    Fillekes, Quirine; Kendall, Lindsay; Kitaka, Sabrina; Mugyenyi, Peter; Musoke, Philippa; Ndigendawani, Milly; Bwakura-Dangarembizi, Mutsa; Gibb, Diana M; Burger, David; Walker, Ann Sarah

    2014-05-01

    Data on zidovudine pharmacokinetics in children dosed using World Health Organization weight bands are limited. About 45 HIV-infected, Ugandan children, 3.4 (2.6-6.2) years, had intensive pharmacokinetic sampling. Geometric mean zidovudine AUC0-12h was 3.0 h.mg/L, which is higher than previously observed in adults, and was independently higher in those receiving higher doses, younger and underweight children. Higher exposure was also marginally associated with lower hemoglobin.

  8. New Labour and Higher Education

    ERIC Educational Resources Information Center

    Watson, David

    2006-01-01

    This paper, the first part of an edited version of a Keynote Presentation delivered at the AUA Annual Conference, Queen's University Belfast, on April 11, 2006, describes the fate of UK higher education during the course of the last parliament and identifies New Labour's two successive and contradictory higher education policies. The author…

  9. The Higher Education Research Archipelago

    ERIC Educational Resources Information Center

    Macfarlane, Bruce

    2012-01-01

    Ever since he stumbled into doing higher education research as a young academic in the 1980s, the author has been trying to understand it as a "field" of study. His career, as a former business lecturer, then an academic developer and now an associate professor for higher education working in an Education Faculty has given him opportunities to see…

  10. The Economy and Higher Education.

    ERIC Educational Resources Information Center

    Anderson, Richard E.

    1988-01-01

    The macroeconomic trends shaping the United States economy and the effects of those trends on higher education are considered. Warning institutions of higher education about possible problems in the economy will place them in a better position to react if necessary. The economic environment is discussed in terms of productivity (goods and services…

  11. "Accessions": Researching, Designing Higher Education

    ERIC Educational Resources Information Center

    Taylor, Yvette

    2011-01-01

    This brief viewpoint piece depicts educational (dis)engagements apparent in researching and (re)designing higher education in and through "Accessions". "Accessions", a collaborative research-design project, probed at how cultures, climates and conditions of higher education may be reproducing or reshaping social inequalities and divisions. Here,…

  12. Theorising Quality in Higher Education

    ERIC Educational Resources Information Center

    Morley, Louise

    2004-01-01

    Britain now has the most heavily regulated higher education system in the world and institutions must deliver best educational value. This book explores the political and psychic economy of quality assurance in higher education and interrogates the discourse and practices associated with the audit culture in Britain. Following Acknowledgements and…

  13. Disability Discrimination in Higher Education.

    ERIC Educational Resources Information Center

    Weber, Mark C.

    1999-01-01

    Reviewed 1998 and early 1999 court decisions related to disability discrimination in higher education. This period witnessed major developments in the law of disability discrimination as it relates to higher education. A major focus was on whether persons whose impairments are ameliorated by treatment are individuals with disabilities covered by…

  14. Asian Americans and Higher Education.

    ERIC Educational Resources Information Center

    Endo, Russell

    Unfortunately the story of Asian Americans and higher education is not one of unqualified success. This paper attempts to overview the historical significance and present the problems of Asian Americans in higher education. The first problem is the lack of oral and writing skills among Asian Americans. Part of this problem is cultural, referring…

  15. Disruptive Technologies in Higher Education

    ERIC Educational Resources Information Center

    Flavin, Michael

    2012-01-01

    This paper analyses the role of "disruptive" innovative technologies in higher education. In this country and elsewhere, Higher Education Institutions (HEIs) have invested significant sums in learning technologies, with Virtual Learning Environments (VLEs) being more or less universal, but these technologies have not been universally adopted and…

  16. Funding Higher Education: Student Perspectives.

    ERIC Educational Resources Information Center

    Mason, Selena; Harvey, Lee

    This report documents the results of a survey of 1,139 students at the University of Central England (UCE) in Birmingham in regard to their financial circumstances and their views on the funding of higher education. The report also examines the advantages and disadvantages of six specific higher education funding proposals put forth in recent…

  17. Higher Education, Poverty and Development

    ERIC Educational Resources Information Center

    Tilak, Jandhyala B. G.

    2010-01-01

    There is a presumption among many policy makers that higher education is not necessary for economic growth and development; it is literacy and basic education and at best secondary education that are argued to be important. Estimates of internal rate of return contributed to strengthening of such a presumption. Accordingly, higher education has…

  18. History of American Higher Education

    ERIC Educational Resources Information Center

    McCarthy, Margaret Cain

    2011-01-01

    "History of American Higher Education" documents the fascinating evolution of American colleges and universities, touching on the historical events that shaped them, from the colonial era through the early twenty-first century. Throughout history, higher education has played an important role in the transmission of cultural identity from one…

  19. Personnel Management in Higher Education.

    ERIC Educational Resources Information Center

    Millett, John D.; And Others

    This document on personnel management in higher education contains three papers that are designed to be used as guidelines for educational administrators. The first two papers, by John D. Millett, discuss the scope and problems of higher education administration and the problems associated with collective bargaining and tenure on college campuses.…

  20. Fact Book on Higher Education

    ERIC Educational Resources Information Center

    Marks, Joseph L.; Diaz, Alicia A.

    2009-01-01

    The "Southern Regional Education Board (SREB) Fact Book on Higher Education" is one of the nation's most comprehensive collections of comparative data on higher education. For decades, state leaders, policy-makers, researchers and journalists have used the "Fact Book" to find useful data quickly--and to learn more about long-term trends and…

  1. Alternative Models for Higher Education.

    ERIC Educational Resources Information Center

    Caffrey, John G.

    Higher education is beset from all sides by criticism, fear, doubt, uncertainty, and prophecies of doom. While the young call for change, the faculty often resist anything that might reduce their privileges and prerogatives. Before alternative models to the present system of higher education can be considered, it is useful to question present…

  2. Exploring Higher Education Financing Options

    ERIC Educational Resources Information Center

    Nkrumah-Young, Kofi K.; Powell, Philip

    2011-01-01

    Higher education can be financed privately, financed by governments, or shared. Given that the benefits of education accrue to the individual and the state, many governments opt for shared financing. This article examines the underpinnings of different options for financing higher education and develops a model to compare conditions to choices and…

  3. Sexual Harassment in Higher Education.

    ERIC Educational Resources Information Center

    Truax, Anne; And Others

    1989-01-01

    An article and three responses on sexual harassment in higher education are presented: "Sexual Harassment in Higher Education: What We've Learned" (Anne Truax); "Who Is Responsible for Sexual Harassment?" (Barbara G. Taylor); "The Feminist-Unionist Dilemma" (Sherna Berger Gluck); and "Sexual Harassment and Academic Power" (Loralee MacPike). (MLW)

  4. Postmodernism in Higher Educational Administration

    ERIC Educational Resources Information Center

    Demaris, Michalyn C.; Kritsonis, William Allan

    2007-01-01

    Postmodernism has many inferences that can be applied to the theory and practice of higher educational administration. Today, in higher education administrators are continuously focused on strategies that will ensure the future of minority educational institutions. As a result postmodernism is an important factor in the future of higher…

  5. Queering Transformation in Higher Education

    ERIC Educational Resources Information Center

    Msibi, Thabo

    2013-01-01

    Transformation in higher education has tended to focus on race and sex, at the expense of other forms of discrimination. This article addresses the silencing of "queer" issues in higher education. Using queer theory as a framework, and drawing on current literature, popular media reports, two personal critical incidents and a project…

  6. Effective Communication in Higher Education

    ERIC Educational Resources Information Center

    Howard, Melissa

    2014-01-01

    The intent for this paper is to show that communication within the higher education field is a current problem. By looking first at the different styles, forms, and audiences for communication, the reader will hopefully gain perspective as to why this is such a problem in higher education today. Since the Millennial generation is the newest set of…

  7. Higher Education, Employability and Competitiveness

    ERIC Educational Resources Information Center

    Pavlin, Samo; Svetlicic, Marjan

    2012-01-01

    This paper studies the relationship between competitiveness and higher education systems in Europe. It explores whether more competitive countries have developed more labour-market-oriented systems of higher education (HE) that thereby give their graduates greater short term employability potential. Based on and a large-scale survey among 45.000…

  8. Strategic Planning for Higher Education.

    ERIC Educational Resources Information Center

    Kotler, Philip; Murphy, Patrick E.

    1981-01-01

    The framework necessary for achieving a strategic planning posture in higher education is outlined. The most important benefit of strategic planning for higher education decision makers is that it forces them to undertake a more market-oriented and systematic approach to long- range planning. (Author/MLW)

  9. The Marketing of Higher Education.

    ERIC Educational Resources Information Center

    Brooker, George; Noble, Michael

    1985-01-01

    Formal college and university marketing programs are challenging to develop and implement because of the complexity of the marketing mix, the perceived inappropriateness of a traditional marketing officer, the number of diverse groups with input, the uniqueness of higher education institutions, and the difficulty in identifying higher education…

  10. Higher Education: Open for Business

    ERIC Educational Resources Information Center

    Gilde, Christian, Ed.

    2007-01-01

    This book addresses a problem in higher learning, which is newly recognized in the academic spotlight: the overcommercialization of higher education. The book asks that you, the reader, think about the following: Did you go to a Coke or Pepsi school? Do your children attend a Nike or Adidas school? Is the college in your town a Dell or Gateway…

  11. Women in Higher Education, 1994.

    ERIC Educational Resources Information Center

    Wenninger, Mary Dee, Ed.

    1994-01-01

    This document consists of the 12 monthly issues of a newsletter on women students, teachers, and administrators in higher education, issued in 1994. Each issue includes feature articles, news on higher education, profiles of significant people in the field, and job announcements. The issues' main article topics are: (1) campuses's changing…

  12. Empowering Women in Higher Education.

    ERIC Educational Resources Information Center

    Wisker, Gina

    This book focuses on enabling and empowering women in higher education, and it draws both on research and experience with women-centered teaching and learning practices and professional development and training of women staff. The first section of the book concentrates on women students in higher education. Chapters include: "Women Students and…

  13. THE ECONOMICS OF HIGHER EDUCATION.

    ERIC Educational Resources Information Center

    CARTTER, ALLAN M.; AND OTHERS

    THIS PUBLICATION CONTAINS PAPERS PRESENTED AT A COLLOQUIUM HELD BY THE COLLEGE SCHOLARSHIP SERVICE IN 1965. THE PAPERS DEAL BROADLY WITH THE QUESTION OF THE MOST EFFECTIVE METHODS OF FINANCING HIGHER EDUCATION, AND WITH THE ROLE AND PROBLEMS OF THE EDUCATIONAL CONSUMER. THE PAPERS DEAL WITH--(1) THE ECONOMICS OF HIGHER EDUCATION, (2) PRICING…

  14. Higher Education in New York.

    ERIC Educational Resources Information Center

    Lane, Frederick, Ed.

    1983-01-01

    New York State higher education policy and finance are discussed in four articles. In "Higher Education and Public Policy in New York," Frederick S. Lane considers the state's institutions, policymakers and politics, financing of colleges, enrollment patterns, links to economic development, and the changing educational environment. Paul T.…

  15. Higher Education and Social Commitment.

    ERIC Educational Resources Information Center

    Nasution, S.; Virasai, Banphot, Eds.

    The proceedings of the Regional Institute of Higher Education and Development's seminar and the meaning and implications of social commitment in higher education are reported. The welcoming address (S. Nasution) and the opening address (Y. B. Dato' Murad bin Mohd. Noor) welcome the participants and set the tone for the discussions to follow. The…

  16. Learning Entrepreneurship in Higher Education

    ERIC Educational Resources Information Center

    Taatila, Vesa P.

    2010-01-01

    Purpose: There is a constant need to produce more entrepreneurial graduates from higher education institutions. This paper aims to present and discuss several successful cases of entrepreneurial learning environments in order to suggest some important aspects that higher education institutions should consider. Design/methodology/approach: The…

  17. The Higher Learning in America.

    ERIC Educational Resources Information Center

    Hutchins, Robert M.

    1999-01-01

    Analysis of the state of public higher education in the United States focuses on government financing of higher education, the high costs of both government and good education, and student attitudes toward their education. A new general education curriculum design at the University of Chicago (Illinois), designed to alleviate some of these…

  18. Innovations in Higher Education? Hah!

    ERIC Educational Resources Information Center

    Kirschner, Ann

    2012-01-01

    One can hardly mention higher education today without hearing the word "innovation," or its understudies "change," "reinvention," "transformation." Last summer the National Governors Association opened its meeting with a plenary session on higher education, innovation, and economic growth. But there is nothing funny about the need for innovation…

  19. Econometric Studies of Higher Education.

    ERIC Educational Resources Information Center

    Ehrenberg, Ronald G.

    The econometrics of higher education emerged from the development of human capital theory and efforts to estimate rates of return to education in the 1960s and 1970s. This paper surveys the various strands of the literature on the econometrics of higher education that have developed during the last 40 years and indicates how a collection of papers…

  20. Higher Education Funding in Missouri

    ERIC Educational Resources Information Center

    Mueller, Lori

    2011-01-01

    The purpose of this qualitative case study was to examine perceptions of state legislators regarding funding of public higher education in the State of Missouri. To this end, I sought to determine how Missouri legislators perceive the purpose of higher education and the role the state government should play in funding it. The concept that higher…

  1. Unexploited Efficiencies in Higher Education

    ERIC Educational Resources Information Center

    Eyring, Henry C.

    2011-01-01

    In "Unexploited Efficiencies in Higher Education," Henry C. Eyring, a junior majoring in Economics at Brigham Young University-Idaho, argues that one way that the U.S. can compete globally in college attainment is to decrease cost-per-graduate. He explains how many stakeholders in higher education stand to benefit from unexploited…

  2. Assessment Issues in Higher Education.

    ERIC Educational Resources Information Center

    Atkins, M. J.; And Others

    This report reviews assessment issues from a British perspective with particular regard to the implications that the National Vocational Qualification (NVQ) Framework will have for assessment in higher education. It considers assessment in relation to the various purposes of higher education and puts forward a number of practical suggestions for…

  3. Higher Education: An International Perspective.

    ERIC Educational Resources Information Center

    Phelps, Richard P.; Dietrich, Greta L.; Phillips, Gabriele; McCormack, Kevin A.

    This report provides a review of higher education systems in selected developed countries and compares higher education in the United States and other countries. The report draws on data from the Indicators of National Education Systems Project of the Centre for Educational Research and Innovation (CERI) of the Organisation for Economic…

  4. Strategy Process in Higher Education

    ERIC Educational Resources Information Center

    Kettunen, Juha

    2010-01-01

    Higher education institutions educate those who are the most talented and best able to secure the future for the next generation. This study examines an efficient strategy process in higher education and emphasises the importance of sufficient dialogue during the process. The study describes the strategy process of the Turku University of Applied…

  5. Higher Education in the Netherlands.

    ERIC Educational Resources Information Center

    de Moor, R. A.

    There are two sectors of higher education in the Netherlands: the universities covered by the University Education Act and the vocationally-oriented colleges covered by the Further Education Act. Following a summary of the main elements of secondary education, higher or tertiary education is defined. Thirteen universities and non-university…

  6. Minority Access to Higher Education

    ERIC Educational Resources Information Center

    Jackson, Nathaniel

    2012-01-01

    Blacks, Hispanics, Native Americans, and Asian Americans are entitled to equal access to all institutions of higher education. Ensuring greater access and participation by minorities in higher education is one of the most practical ways of moving America closer to the ideal of equal opportunity, which is the actualization of the American dream.…

  7. Does Higher Education Need Deschooling?

    ERIC Educational Resources Information Center

    Butson, Russell

    2011-01-01

    This paper presents an attempt to overcome the contemporary obsession with "learning" and proposes that current practices in higher education are aligned too closely with the educational theories and practices developed within pre-university compulsory education. The author takes the position that higher education is substantially different from…

  8. Feminist Research in Higher Education

    ERIC Educational Resources Information Center

    Ropers-Huilman, Rebecca; Winters, Kelly T.

    2011-01-01

    This essay provides an overview of feminist methodology and its potential to enhance the study of higher education. Foregrounding the multiple purposes and research relationships developed through feminist research, the essay urges higher education scholars to engage feminist theories, epistemologies, and methods to inform policy, research, and…

  9. Confectionery-based dose forms.

    PubMed

    Tangso, Kristian J; Ho, Quy Phuong; Boyd, Ben J

    2015-01-01

    Conventional dosage forms such as tablets, capsules and syrups are prescribed in the normal course of practice. However, concerns about patient preferences and market demands have given rise to the exploration of novel unconventional dosage forms. Among these, confectionery-based dose forms have strong potential to overcome compliance problems. This report will review the availability of these unconventional dose forms used in treating the oral cavity and for systemic drug delivery, with a focus on medicated chewing gums, medicated lollipops, and oral bioadhesive devices. The aim is to stimulate increased interest in the opportunities for innovative new products that are available to formulators in this field, particularly for atypical patient populations. PMID:25146440

  10. Organ doses to adult patients for chest CT

    SciTech Connect

    Huda, Walter; Sterzik, Alexander; Tipnis, Sameer; Schoepf, U. Joseph

    2010-02-15

    {approx}20 cm for a 50 kg patient and {approx}28 cm for a 100 kg patient. At constant x-ray techniques, a 50 kg patient is expected to have doses that are {approx}18% higher than those in a 70 kg adult, whereas a 100 kg patient will have doses that are {approx}18% lower. Conclusions: We describe a practical method to use CTDI data provided by commercial CT scanners to obtain patient and examination specific estimates of organ dose for chest CT examinations.

  11. Hypoxia Dose Painting by Numbers: A Planning Study

    SciTech Connect

    Thorwarth, Daniela . E-mail: daniela.thorwarth@med.uni-tuebingen.de; Eschmann, Susanne-Martina; Paulsen, Frank; Alber, Markus

    2007-05-01

    Purpose: To investigate the feasibility of different hypoxia dose painting strategies in head-and-neck radiotherapy; the potential benefit was limited by the stipulation of isotoxicity with respect to the conventional intensity-modulated radiotherapy (IMRT) treatment. Methods and Materials: Thirteen head-and-neck cancer patients were included into the planning study. For each patient, three different treatment plans were created: a conventional IMRT plan, an additional uniform dose escalation (uniDE) of 10% to the fluorodeoxyglucose (FDG)-positive volume, and a plan in which dose painting by numbers (DPBN) was implemented. Dose painting by numbers was realized according to a map of dose-escalation factors calculated from dynamic [{sup 18}F]-fluoromisonidazole (FMISO) positron emission tomography data. Results: Both dose-escalation approaches were shown to be feasible under the constraint of limiting normal tissue doses to the level of conventional IMRT. For DPBN, the prescriptions could be fulfilled in larger regions of the target than for uniDE. Fluorodeoxyglucose-positive volumes had sizes up to 94 cm{sup 3}. In contrast, regions receiving comparable dose levels with DPBN presented volumes in the range of 0-2.7 cm{sup 3}. Overtreatment of the target was observed with uniDE in most of the cases, whereas some regions did not receive the required dose to overcome hypoxia-induced radiation insensitivity. Tumor control probability increased from 55.9% with conventional IMRT to 57.7% for the uniDE method in the patient group. For DPBN, a potential increase in tumor control probability from 55.9% to 70.2% was determined. Therefore, DPBN seems to result in higher benefits for the patients. Conclusion: Dose painting by numbers delivers the dose more effectively than an additional uniform boost to the FDG-positive area. If hypoxia could be adequately quantified with a simple imaging technique like FMISO positron emission tomography, DPBN in head-and-neck cancer could

  12. Atmospheric radiation flight dose rates

    NASA Astrophysics Data System (ADS)

    Tobiska, W. K.

    2015-12-01

    Space weather's effects upon the near-Earth environment are due to dynamic changes in the energy transfer processes from the Sun's photons, particles, and fields. Of the domains that are affected by space weather, the coupling between the solar and galactic high-energy particles, the magnetosphere, and atmospheric regions can significantly affect humans and our technology as a result of radiation exposure. Space Environment Technologies (SET) has been conducting space weather observations of the atmospheric radiation environment at aviation altitudes that will eventually be transitioned into air traffic management operations. The Automated Radiation Measurements for Aerospace Safety (ARMAS) system and Upper-atmospheric Space and Earth Weather eXperiment (USEWX) both are providing dose rate measurements. Both activities are under the ARMAS goal of providing the "weather" of the radiation environment to improve aircraft crew and passenger safety. Over 5-dozen ARMAS and USEWX flights have successfully demonstrated the operation of a micro dosimeter on commercial aviation altitude aircraft that captures the real-time radiation environment resulting from Galactic Cosmic Rays and Solar Energetic Particles. The real-time radiation exposure is computed as an effective dose rate (body-averaged over the radiative-sensitive organs and tissues in units of microsieverts per hour); total ionizing dose is captured on the aircraft, downlinked in real-time, processed on the ground into effective dose rates, compared with NASA's Langley Research Center (LaRC) most recent Nowcast of Atmospheric Ionizing Radiation System (NAIRAS) global radiation climatology model runs, and then made available to end users via the web and smart phone apps. Flight altitudes now exceed 60,000 ft. and extend above commercial aviation altitudes into the stratosphere. In this presentation we describe recent ARMAS and USEWX results.

  13. Radiation dose from cigarette tobacco

    SciTech Connect

    Papastefanou, C.

    2008-08-07

    The radioactivity in tobacco leaves collected from 15 different regions of Greece before cigarette production was studied in order to estimate the effective dose from cigarette tobacco due to the naturally occurring primordial radionuclides, such as {sup 226}Ra and {sup 210}Pb of the uranium series and {sup 228}Ra of the thorium series and/or man-made produced radionuclides, such as {sup 137}Cs of Chernobyl origin. Gamma-ray spectrometry was applied using Ge planar and coaxial type detectors of high resolution and high efficiency. It was concluded that the annual effective dose due to inhalation for adults (smokers) for {sup 226}Ra varied from 42.5 to 178.6 {mu}Sv y{sup -1} (average 79.7 {mu}Sv y{sup -1}), while for {sup 228}Ra from 19.3 to 116.0 {mu}Sv y{sup -1} (average 67.1 {mu}Sv y{sup -1}) and for {sup 210}Pb from 47.0 to 134.9 {mu}Sv y{sup -1} (average 104.7 {mu}Sv y{sup -1}), that is the same order of magnitude for each radionuclide. The sum of the effective dose of the three natural radionuclides varied from 151.9 to 401.3 {mu}Sv y{sup -1} (average 251.5 {mu}Sv y{sup -1}). The annual effective dose from {sup 137}Cs of Chernobyl origin was three orders of magnitude lower as it varied from 70.4 to 410.4 nSv y{sup -1} (average 199.3 nSv y{sup -1})

  14. Dosing dilemmas in obese children.

    PubMed

    Mulla, H; Johnson, T N

    2010-08-01

    With the epidemic of childhood obesity, it is not uncommon for prescribers to puzzle over an appropriate drug dose for an obese child. Defining the optimum therapeutic dose of a drug relies on an understanding of pharmacokinetics and pharmacodynamics. Both these processes can be affected by body composition and the physiological changes that occur in obese children. As a rule of thumb, 75% of excess weight in obese subjects is fat mass, and the remainder lean mass. Although it is reasonable to assume that increases in fat mass alter the distribution of lipophilic drugs and increases in lean mass alter drug clearance, good quality and consistent clinical data supporting these assumptions are lacking for the majority of drugs. The relatively few clinical studies that have evaluated the impact of obesity have often been limited by poor design and insufficient sample size. Moreover, clinical studies conducted during drug development rarely include (or are required to include) obese subjects. Guidance on dosing obese children ought to be provided by drug manufacturers. This could be achieved by including obese patients in studies where possible, enabling the effect of body size on pharmacotherapy to be evaluated. This approach could be further augmented by the use of physiologically based-pharmacokinetic models during early (preclinical) development to predict the impact of obesity on drug disposition, and subsequent clinical studies later in development to provide confirmatory proof. In the meantime, for the majority of drugs already prescribed in children, particularly those where the therapeutic range is narrow or there is significant toxicity, the lack of a validated body size descriptor to use at the bedside means the choice of dose will rely on empirical experience and application of the precautionary principle. PMID:20585055

  15. 5-ASA Dose-Response

    PubMed Central

    Katz, Seymour; Lichtenstein, Gary R; Safdi, Michael A

    2010-01-01

    Mesalamine (5-aminosalicylic acid; 5-ASA) represents the cornerstone of first-line therapy for mild-to-moderate ulcerative colitis (UC). Current guidelines suggest that the combination of oral and rectal therapies provide optimal symptom resolution and effectively maintain remission in the majority of these patients. Although effective, most oral 5-ASA formulations have a high pill burden and rectal therapies are associated with low adherence. Recent research has examined patterns of compliance, as well as the efficacy of different dose levels of 5-ASA in terms of symptom resolution, the maintenance of remission, and improvements in quality of life. The ASCEND I, II, and III trials found that doses of 4.8 g/day are more effective than 2.4 g/day doses in patients with moderate disease, those with previous steroid use, and those with a history of multiple medications. The benefits of effective long-term 5-ASA therapy include the avoidance of more costly and potentially toxic drugs (such as corticosteroids and biologic therapies), as well as improvements in quality of life, reductions in the need for future colectomy, and a lower risk of developing colorectal cancer. PMID:20567558

  16. Tolerance doses for treatment planning

    SciTech Connect

    Lyman, J.T.

    1985-10-01

    Data for the tolerance of normal tissues or organs to (low-LET) radiation has been compiled from a number of sources which are referenced at the end of this document. This tolerance dose data are ostensibly for uniform irradiation of all or part of an organ, and are for either 5% (TD/sub 5/) or 50% (TD/sub 50/) complication probability. The ''size'' of the irradiated organ is variously stated in terms of the absolute volume or the fraction of the organ volume irradiated, or the area or the length of the treatment field. The accuracy of these data is questionable. Much of the data represents doses that one or several experienced therapists have estimated could be safely given rather than quantitative analyses of clinical observations. Because these data have been obtained from multiple sources with possible different criteria for the definition of a complication, there are sometimes different values for what is apparently the same endpoint. The data from some sources shows a tendancy to be quantized in 5 Gy increments. This reflects the size of possible round off errors. It is believed that all these data have been accumulated without the benefit of 3-D dose distributions and therefore the estimates of the size of the volume and/or the uniformity of the irradiation may be less accurate than is now possible. 19 refs., 4 figs.

  17. On higher holonomy invariants in higher gauge theory II

    NASA Astrophysics Data System (ADS)

    Zucchini, Roberto

    2016-06-01

    This is the second of a series of two technical papers devoted to the analysis of holonomy invariants in strict higher gauge theory with end applications in higher Chern-Simons theory. We provide a definition of trace over a crossed module to yield surface knot invariants upon application to 2-holonomies. We show further that the properties of the trace are best described using the theory quandle crossed modules.

  18. Dose rate mapping of VMAT treatments

    NASA Astrophysics Data System (ADS)

    Podesta, Mark; Antoniu Popescu, I.; Verhaegen, Frank

    2016-06-01

    Human tissues exhibit a varying response to radiation dose depending on the dose rate and fractionation scheme used. Dose rate effects have been reported for different radiations, and tissue types. The literature indicates that there is not a significant difference in response for low-LET radiation when using dose rates between 1 Gy min‑1 and 12 Gy min‑1 but lower dose rates have an observable sparing effect on tissues and a differential effect between tissues. In intensity-modulated radiotherapy such as volumetric modulated arc therapy (VMAT) the dose can be delivered with a wide range of dose rates. In this work we developed a method based on time-resolved Monte Carlo simulations to quantify the dose rate frequency distribution for clinical VMAT treatments for three cancer sites, head and neck, lung, and pelvis within both planning target volumes (PTV) and normal tissues. The results show a wide range of dose rates are used to deliver dose in VMAT and up to 75% of the PTV can have its dose delivered with dose rates  <1 Gy min‑1. Pelvic plans on average have a lower mean dose rate within the PTV than lung or head and neck plans but a comparable mean dose rate within the organs at risk. Two VMAT plans that fulfil the same dose objectives and constraints may be delivered with different dose rate distributions, particularly when comparing single arcs to multiple arc plans. It is concluded that for dynamic plans, the dose rate range used varies to a larger degree than previously assumed. The effect of the dose rate range in VMAT on clinical outcome is unknown.

  19. Dose rate mapping of VMAT treatments

    NASA Astrophysics Data System (ADS)

    Podesta, Mark; Antoniu Popescu, I.; Verhaegen, Frank

    2016-06-01

    Human tissues exhibit a varying response to radiation dose depending on the dose rate and fractionation scheme used. Dose rate effects have been reported for different radiations, and tissue types. The literature indicates that there is not a significant difference in response for low-LET radiation when using dose rates between 1 Gy min-1 and 12 Gy min-1 but lower dose rates have an observable sparing effect on tissues and a differential effect between tissues. In intensity-modulated radiotherapy such as volumetric modulated arc therapy (VMAT) the dose can be delivered with a wide range of dose rates. In this work we developed a method based on time-resolved Monte Carlo simulations to quantify the dose rate frequency distribution for clinical VMAT treatments for three cancer sites, head and neck, lung, and pelvis within both planning target volumes (PTV) and normal tissues. The results show a wide range of dose rates are used to deliver dose in VMAT and up to 75% of the PTV can have its dose delivered with dose rates  <1 Gy min-1. Pelvic plans on average have a lower mean dose rate within the PTV than lung or head and neck plans but a comparable mean dose rate within the organs at risk. Two VMAT plans that fulfil the same dose objectives and constraints may be delivered with different dose rate distributions, particularly when comparing single arcs to multiple arc plans. It is concluded that for dynamic plans, the dose rate range used varies to a larger degree than previously assumed. The effect of the dose rate range in VMAT on clinical outcome is unknown.

  20. Dose rate mapping of VMAT treatments.

    PubMed

    Podesta, Mark; Popescu, I Antoniu; Verhaegen, Frank

    2016-06-01

    Human tissues exhibit a varying response to radiation dose depending on the dose rate and fractionation scheme used. Dose rate effects have been reported for different radiations, and tissue types. The literature indicates that there is not a significant difference in response for low-LET radiation when using dose rates between 1 Gy min(-1) and 12 Gy min(-1) but lower dose rates have an observable sparing effect on tissues and a differential effect between tissues. In intensity-modulated radiotherapy such as volumetric modulated arc therapy (VMAT) the dose can be delivered with a wide range of dose rates. In this work we developed a method based on time-resolved Monte Carlo simulations to quantify the dose rate frequency distribution for clinical VMAT treatments for three cancer sites, head and neck, lung, and pelvis within both planning target volumes (PTV) and normal tissues. The results show a wide range of dose rates are used to deliver dose in VMAT and up to 75% of the PTV can have its dose delivered with dose rates  <1 Gy min(-1). Pelvic plans on average have a lower mean dose rate within the PTV than lung or head and neck plans but a comparable mean dose rate within the organs at risk. Two VMAT plans that fulfil the same dose objectives and constraints may be delivered with different dose rate distributions, particularly when comparing single arcs to multiple arc plans. It is concluded that for dynamic plans, the dose rate range used varies to a larger degree than previously assumed. The effect of the dose rate range in VMAT on clinical outcome is unknown.

  1. Methaqualone metabolites in human urine after therapeutic doses.

    PubMed

    Kazyak, L; Kelley, J A; Cella, J A; Droege, R E; Hilpert, L R; Permisohn, R C

    1977-11-01

    We measured five principal metabolites of methaqualone in the urine of seven volunteers after single and multiple doses of the drug. Urine, collected for up to 72 hours after the last dose, was analyzed for methaqualone and its principal metabolites by high-resolution capillary-column gas chromatography. The major biotransformation of methaqualone under therapeutic conditions occurred through benzylic and para-hydroxylation of the o-tolyl moiety. Methaqualone itself was present in concentrations of no more than 1 mg/liter, if it could be detected at all. The observed physiological effects ant total urinary excretion of metabolites reflected the cumulative nature of the parent drug when it was administered in multiple doses. No clear relationship was found between appearance of a specific metabolite and time after ingestion of the drug, although higher amounts of 2-methyl-3-(2'-hydroxymethylphenyl)-4(3H)-quinazolinone were noted in those individuals who tolerated the drug less well.

  2. Deformable Dose Reconstruction to Optimize the Planning and Delivery of Liver Cancer Radiotherapy

    NASA Astrophysics Data System (ADS)

    Velec, Michael

    The precise delivery of radiation to liver cancer patients results in improved control with higher tumor doses and minimized normal tissues doses. A margin of normal tissue around the tumor requires irradiation however to account for treatment delivery uncertainties. Daily image-guidance allows targeting of the liver, a surrogate for the tumor, to reduce geometric errors. However poor direct tumor visualization, anatomical deformation and breathing motion introduce uncertainties between the planned dose, calculated on a single pre-treatment computed tomography image, and the dose that is delivered. A novel deformable image registration algorithm based on tissue biomechanics was applied to previous liver cancer patients to track targets and surrounding organs during radiotherapy. Modeling these daily anatomic variations permitted dose accumulation, thereby improving calculations of the delivered doses. The accuracy of the algorithm to track dose was validated using imaging from a deformable, 3-dimensional dosimeter able to optically track absorbed dose. Reconstructing the delivered dose revealed that 70% of patients had substantial deviations from the initial planned dose. An alternative image-guidance technique using respiratory-correlated imaging was simulated, which reduced both the residual tumor targeting errors and the magnitude of the delivered dose deviations. A planning and delivery strategy for liver radiotherapy was then developed that minimizes the impact of breathing motion, and applied a margin to account for the impact of liver deformation during treatment. This margin is 38% smaller on average than the margin used clinically, and permitted an average dose-escalation to liver tumors of 9% for the same risk of toxicity. Simulating the delivered dose with deformable dose reconstruction demonstrated the plans with smaller margins were robust as 90% of patients' tumors received the intended dose. This strategy can be readily implemented with widely

  3. Energy deposition in the breast during CT scanning: quantification and implications for dose reduction

    NASA Astrophysics Data System (ADS)

    Rupcich, Franco; Kyprianou, Iacovos; Badal, Andreu; Schmidt, Taly G.

    2011-03-01

    Studies suggest that dose to the breast leads to a higher lifetime attributable cancer incidence risk from a chest CT scan for women compared to men. Numerous methods have been proposed for reducing dose to the breast during CT scanning, including bismuth shielding, tube current modulation, partial-angular scanning, and reduced kVp. These methods differ in how they alter the spectrum and fluence across projection angle. This study used Monte Carlo CT simulations of a voxelized female phantom to investigate the energy (dose) deposition in the breast as a function of both photon energy and projection angle. The resulting dose deposition matrix was then used to investigate several questions regarding dose reduction to the breast: (1) Which photon energies deposit the most dose in the breast, (2) How does increased filtration compare to tube current reduction in reducing breast dose, and (3) Do reduced kVp scans reduce dose to breast, and if so, by what mechanism? The results demonstrate that while high-energy photons deposit more dose per emitted photon, the low-energy photons deposit more dose to the breast for a 120 kVp acquisition. The results also demonstrate that decreasing the tube current for the AP views to match the fluence exiting a shield deposits nearly the same dose to the breast as when using a shield (within ~1%). Finally, results suggest that the dose reduction observed during lower kVp scans is caused by reduced photon fluence rather than the elimination of high-energy photons from the beam. Overall, understanding the mechanisms of dose deposition in the breast as a function of photon energy and projection angle enables comparisons of dose reduction methods and facilitates further development of optimized dose reduction schemes.

  4. Calculation of dose profiles in stereotactic synchrotron microplanar beam radiotherapy in a tissue-lung phantom.

    PubMed

    Company, F Z

    2007-03-01

    Synchrotron x-ray beams with high fluence rate and highly collimated may be used in stereotactic radiotherapy of lung tumours. A bundle of converging monochromatic x-ray beams having uniform microscopic thickness i.e. (microplanar beams) are directed to the center of the tumour, delivering lethal dose to the target volume while sparing normal cells. The proposed technique takes advantage of the hypothesised repair mechanism of capillary cells between alternate microbeam zones, which regenerate the lethally irradiated endothelial cells. The sharply dropping lateral dose of a microbeam provides low scattered dose to the off-target interbeam volume. In the target volume the converging bundle of beams are closely spaced, and relatively high primary and secondary electron doses overlap and produce a high dose region between the beams. This higher and lower dose margins in the target volume allows precise targeting. The advantages of stereotactic microbeam radiotherapy will be lost as the dose between microbeams exceeds the tolerance dose of the dose limiting tissues. Therefore, it is essential to optimize the interbeam doses in off-target volume. The lateral and depth doses of 100 keV microplanar beams are investigated for a single beam and an array of converging microplanar beams in a tissue, lung and tissue-lung phantoms. The EGS5 Monte Carlo code is used to calculate dose profiles at different depths and bundles of beams. The maximum dose on the beam axis (peak) and the minimum interbeam dose (valley) are compared at different energies, depths, bundle sizes, heights, widths and beam spacings. The interbeam dose is calculated at different depths and an isodose map of the phantom is obtained. An acceptable energy region is found for tissue and lung microbeam radiotherapy and a stereotactic microbeam radiotherapy model is proposed for a 4 cm diameter and 1 cm thick tumour on the lung phantom.

  5. Personalised dosing: Printing a dose of one's own medicine.

    PubMed

    Alomari, Mustafa; Mohamed, Fatima H; Basit, Abdul W; Gaisford, Simon

    2015-10-30

    Ink-jet printing is a versatile, precise and relatively inexpensive method of depositing small volumes of solutions with remarkable accuracy and repeatability. Although developed primarily as a technology for image reproduction, its areas of application have expanded significantly in recent years. It is particularly suited to the manufacture of low dose medicines or to short production runs and so offers a potential manufacturing solution for the paradigm of personalised medicines. This review discusses the technical and clinical aspects of ink-jet printing that must be considered in order for the technology to become widely adopted in the pharmaceutical arena and considers applications in the literature.

  6. Colistin: how should it be dosed for the critically ill?

    PubMed

    Landersdorfer, Cornelia B; Nation, Roger L

    2015-02-01

    Colistin, an "old" polymyxin antibiotic, is increasingly being used as last-line treatment against infections caused by multidrug-resistant gram-negative bacteria. It is administered in patients, parenterally or by inhalation, as its inactive prodrug colistin methanesulfonate (CMS). Scientifically based recommendations on how to optimally dose colistin in critically ill patients have become available over the last decade and are extremely important as colistin has a narrow therapeutic window. A dosing algorithm has been developed to achieve desired plasma colistin concentrations in critically ill patients. This includes the necessary dose adjustments for patients with impaired kidney function and those on renal replacement therapy. Due to the slow conversion of CMS to colistin, a loading dose is needed to generate effective concentrations within a reasonable time period. Therapeutic drug monitoring is warranted, where available; because of the observed high interpatient variability in plasma colistin concentrations. Combination therapy should be considered when the infecting pathogen has a colistin minimum inhibitory concentration above 1 mg/L, as increasing the dose may not be feasible due to the risk for nephrotoxicity. Inhalation of CMS achieves considerably higher colistin concentrations in lung fluids than is possible with intravenous administration, with negligible plasma exposure. Similarly, for central nervous system infections, dosing CMS directly into the cerebrospinal fluid generates significantly higher colistin concentrations at the infection site compared with what can be achieved with systemic administration. While questions remain to be addressed via ongoing research, this article reviews the significant advances that have been made toward optimizing the clinical use of colistin.

  7. Fewer Doses of HPV Vaccine Result in Immune Response Similar to Three-Dose Regimen

    MedlinePlus

    ... Releases NCI News Note Fewer doses of HPV vaccine result in immune response similar to three-dose ... that two doses of a human papillomavirus (HPV) vaccine, trademarked as Cervarix, resulted in similar serum antibody ...

  8. Higher blood flow and circulating NO products offset high-altitude hypoxia among Tibetans.

    PubMed

    Erzurum, S C; Ghosh, S; Janocha, A J; Xu, W; Bauer, S; Bryan, N S; Tejero, J; Hemann, C; Hille, R; Stuehr, D J; Feelisch, M; Beall, C M

    2007-11-01

    The low barometric pressure at high altitude causes lower arterial oxygen content among Tibetan highlanders, who maintain normal levels of oxygen use as indicated by basal and maximal oxygen consumption levels that are consistent with sea level predictions. This study tested the hypothesis that Tibetans resident at 4,200 m offset physiological hypoxia and achieve normal oxygen delivery by means of higher blood flow enabled by higher levels of bioactive forms of NO, the main endothelial factor regulating blood flow and vascular resistance. The natural experimental study design compared Tibetans at 4,200 m and U.S. residents at 206 m. Eighty-eight Tibetan and 50 U.S. resident volunteers (18-56 years of age, healthy, nonsmoking, nonhypertensive, not pregnant, with normal pulmonary function) participated. Forearm blood flow, an indicator of systemic blood flow, was measured noninvasively by using plethysmography at rest, after breathing supplemental oxygen, and after exercise. The Tibetans had more than double the forearm blood flow of low-altitude residents, resulting in greater than sea level oxygen delivery to tissues. In comparison to sea level controls, Tibetans had >10-fold-higher circulating concentrations of bioactive NO products, including plasma and red blood cell nitrate and nitroso proteins and plasma nitrite, but lower concentrations of iron nitrosyl complexes (HbFeIINO) in red blood cells. This suggests that NO production is increased and that metabolic pathways controlling formation of NO products are regulated differently among Tibetans. These findings shift attention from the traditional focus on pulmonary and hematological systems to vascular factors contributing to adaptation to high-altitude hypoxia. PMID:17971439

  9. The impact of inter-fraction dose variations on biological equivalent dose (BED): the concept of equivalent constant dose

    NASA Astrophysics Data System (ADS)

    Zavgorodni, S.

    2004-12-01

    Inter-fraction dose fluctuations, which appear as a result of setup errors, organ motion and treatment machine output variations, may influence the radiobiological effect of the treatment even when the total delivered physical dose remains constant. The effect of these inter-fraction dose fluctuations on the biological effective dose (BED) has been investigated. Analytical expressions for the BED accounting for the dose fluctuations have been derived. The concept of biological effective constant dose (BECD) has been introduced. The equivalent constant dose (ECD), representing the constant physical dose that provides the same cell survival fraction as the fluctuating dose, has also been introduced. The dose fluctuations with Gaussian as well as exponential probability density functions were investigated. The values of BECD and ECD calculated analytically were compared with those derived from Monte Carlo modelling. The agreement between Monte Carlo modelled and analytical values was excellent (within 1%) for a range of dose standard deviations (0-100% of the dose) and the number of fractions (2 to 37) used in the comparison. The ECDs have also been calculated for conventional radiotherapy fields. The analytical expression for the BECD shows that BECD increases linearly with the variance of the dose. The effect is relatively small, and in the flat regions of the field it results in less than 1% increase of ECD. In the penumbra region of the 6 MV single radiotherapy beam the ECD exceeded the physical dose by up to 35%, when the standard deviation of combined patient setup/organ motion uncertainty was 5 mm. Equivalently, the ECD field was ~2 mm wider than the physical dose field. The difference between ECD and the physical dose is greater for normal tissues than for tumours.

  10. Thatcherism and British Higher Education.

    ERIC Educational Resources Information Center

    Shattock, Michael

    1989-01-01

    A discussion of the influence of Britain's prime minister, Margaret Thatcher, on higher education looks at the relationship between the administrator's 10 years in office and the fiscal, educational, and public policy issues currently under debate. (MSE)

  11. Synthesis of higher monocarboxylic acids

    SciTech Connect

    Taikov, B.F.; Novakovskii, E.M.; Zhelkovskaya, V.P.; Shadrova, V.N.; Shcherbik, P.K.

    1981-01-01

    Brown-coal and peat waxes contain higher monocarboxylic acids, alcohols and esters of them as their main components. In view of this, considerable interest is presented by the preparation of individual compounds among those mentioned above, which is particularly important in the study of the composition and development of the optimum variants of the chemical processing of the waxes. In laboratory practice, to obtain higher monocarboxylic acids use is generally made of electrosynthesis according to Kolbe which permits unbranched higher aliphatic acids with given lengths of the hydrocarbon chain to be obtained. The aim of the present work was to synthesize higher monocarboxylic acids: arachidic, behenic, lignoceric, pentacosanoic, erotic, heptacosanoic, montanic, nonacosanoic, melissic, dotriacontanoic and tetratriacontanoic, which are present in waxes. Characteristics of synthesized acids are tabulated. 20 refs.

  12. Solving higher curvature gravity theories

    NASA Astrophysics Data System (ADS)

    Chakraborty, Sumanta; SenGupta, Soumitra

    2016-10-01

    Solving field equations in the context of higher curvature gravity theories is a formidable task. However, in many situations, e.g., in the context of f( R) theories, the higher curvature gravity action can be written as an Einstein-Hilbert action plus a scalar field action. We show that not only the action but the field equations derived from the action are also equivalent, provided the spacetime is regular. We also demonstrate that such an equivalence continues to hold even when the gravitational field equations are projected on a lower-dimensional hypersurface. We have further addressed explicit examples in which the solutions for Einstein-Hilbert and a scalar field system lead to solutions of the equivalent higher curvature theory. The same, but on the lower-dimensional hypersurface, has been illustrated in the reverse order as well. We conclude with a brief discussion on this technique of solving higher curvature field equations.

  13. Higher Education: Labor Market Linkage.

    ERIC Educational Resources Information Center

    Asayeghn, Desta

    1982-01-01

    Examines the methodology of three case studies investigating the linkage between higher education and the world of work in the Sudan, Zambia, and Tanzania. Summarizes 12 main findings. Suggests the studies remain traditional human resources planning efforts. (NEC)

  14. Staff Radiation Doses to the Lower Extremities in Interventional Radiology

    SciTech Connect

    Shortt, C. P.; Al-Hashimi, H.; Malone, L.; Lee, M. J.

    2007-11-15

    The purpose of this study was to investigate the radiation doses to the lower extremities in interventional radiology suites and evaluate the benefit of installation of protective lead shielding. After an alarmingly increased dose to the lower extremity in a preliminary study, nine interventional radiologists wore thermoluminescent dosimeters (TLDs) just above the ankle, over a 4-week period. Two different interventional suites were used with Siemens undercouch fluoroscopy systems. A range of procedures was carried out including angiography, embolization, venous access, drainages, and biopsies. A second identical 4-week study was then performed after the installation of a 0.25-mm lead curtain on the working side of each interventional table. Equivalent doses for all nine radiologists were calculated. One radiologist exceeded the monthly dose limit for a Category B worker (12.5 mSv) for both lower extremities before lead shield placement but not afterward. The averages of both lower extremities showed a statistically significant dose reduction of 64% (p < 0.004) after shield placement. The left lower extremity received a higher dose than the right, 6.49 vs. 4.57 mSv, an increase by a factor of 1.42. Interventional radiology is here to stay but the benefits of interventional radiology should never distract us from the important issue of radiation protection. All possible measures should be taken to optimize working conditions for staff. This study showed a significant lower limb extremity dose reduction with the use of a protective lead curtain. This curtain should be used routinely on all C-arm interventional radiologic equipment.

  15. Microsieving in primary treatment: effect of chemical dosing.

    PubMed

    Väänänen, J; Cimbritz, M; la Cour Jansen, J

    2016-01-01

    Primary and chemically enhanced primary wastewater treatment with microsieving (disc or drum filtration) was studied at the large pilot scale at seven municipal wastewater treatment plants in Europe. Without chemical dosing, the reduction of suspended solids (SS) was (on average) 50% (20-65%). By introducing chemically enhanced primary treatment and dosing with cationic polymer only, SS removal could be controlled and increased to >80%. A maximum SS removal of >90% was achieved with a chemical dosing of >0.007 mg polymer/mg influent SS and 20 mg Al(3+)/L or 30 mg Fe(3+)/L. When comparing sieve pore sizes of 30-40 μm with 100 μm, the effluent SS was comparable, indicating that the larger sieve pore size could be used due to the higher loading capacity for the solids. Phosphorus removal was adjusted with the coagulant dose, and a removal of 95-97% was achieved. Moreover, microsieving offers favourable conditions for automated dosing control due to the low retention time in the filter. PMID:27438249

  16. Fast convolution-superposition dose calculation on graphics hardware.

    PubMed

    Hissoiny, Sami; Ozell, Benoît; Després, Philippe

    2009-06-01

    The numerical calculation of dose is central to treatment planning in radiation therapy and is at the core of optimization strategies for modern delivery techniques. In a clinical environment, dose calculation algorithms are required to be accurate and fast. The accuracy is typically achieved through the integration of patient-specific data and extensive beam modeling, which generally results in slower algorithms. In order to alleviate execution speed problems, the authors have implemented a modern dose calculation algorithm on a massively parallel hardware architecture. More specifically, they have implemented a convolution-superposition photon beam dose calculation algorithm on a commodity graphics processing unit (GPU). They have investigated a simple porting scenario as well as slightly more complex GPU optimization strategies. They have achieved speed improvement factors ranging from 10 to 20 times with GPU implementations compared to central processing unit (CPU) implementations, with higher values corresponding to larger kernel and calculation grid sizes. In all cases, they preserved the numerical accuracy of the GPU calculations with respect to the CPU calculations. These results show that streaming architectures such as GPUs can significantly accelerate dose calculation algorithms and let envision benefits for numerically intensive processes such as optimizing strategies, in particular, for complex delivery techniques such as IMRT and are therapy.

  17. Thermoluminescent dosimeters for low dose X-ray measurements.

    PubMed

    Fernández, S Del Sol; García-Salcedo, R; Sánchez-Guzmán, D; Ramírez-Rodríguez, G; Gaona, E; de León-Alfaro, M A; Rivera-Montalvo, T

    2016-01-01

    The response of TLD-100, CaSO4:Dy and LiF:Mg,Cu,P for a range of X-ray low dose was measured. For calibration, the TLDs were arranged at the center of the X-ray field. The dose output of the X-ray machine was determined using an ACCU-Gold. All dosimeters were exposed at the available air kerma values of 14.69 mGy within a field 10×10 cm(2) at 80 cm of SSD. Results of LiF:Mg,Cu,P X-ray irradiated showed 4.8 times higher sensitivity than TLD-100. Meanwhile, TL response of CaSO4:Dy exposed at the same dose was 5.6 time higher than TLD-100. Experimental results show for low dose X-ray measurements a better linearity for LiF:Mg,Cu,P compared with that of TLD-100. CaSO4:Dy showed a linearity from 0.1 to 60 mGy.

  18. Thermoluminescent dosimeters for low dose X-ray measurements.

    PubMed

    Fernández, S Del Sol; García-Salcedo, R; Sánchez-Guzmán, D; Ramírez-Rodríguez, G; Gaona, E; de León-Alfaro, M A; Rivera-Montalvo, T

    2016-01-01

    The response of TLD-100, CaSO4:Dy and LiF:Mg,Cu,P for a range of X-ray low dose was measured. For calibration, the TLDs were arranged at the center of the X-ray field. The dose output of the X-ray machine was determined using an ACCU-Gold. All dosimeters were exposed at the available air kerma values of 14.69 mGy within a field 10×10 cm(2) at 80 cm of SSD. Results of LiF:Mg,Cu,P X-ray irradiated showed 4.8 times higher sensitivity than TLD-100. Meanwhile, TL response of CaSO4:Dy exposed at the same dose was 5.6 time higher than TLD-100. Experimental results show for low dose X-ray measurements a better linearity for LiF:Mg,Cu,P compared with that of TLD-100. CaSO4:Dy showed a linearity from 0.1 to 60 mGy. PMID:26609683

  19. Mechanisms of Low Dose Radio-Suppression of Genomic Instability

    SciTech Connect

    Engelward, Bevin P

    2009-09-16

    The major goal of this project is to contribute toward the elucidation of the impact of long term low dose radiation on genomic stability. We have created and characterized novel technologies for delivering long term low dose radiation to animals, and we have studied genomic stability by applying cutting edge molecular analysis technologies. Remarkably, we have found that a dose rate that is 300X higher than background radiation does not lead to any detectable genomic damage, nor is there any significant change in gene expression for genes pertinent to the DNA damage response. These results point to the critical importance of dose rate, rather than just total dose, when evaluating public health risks and when creating regulatory guidelines. In addition to these studies, we have also further developed a mouse model for quantifying cells that have undergone a large scale DNA sequence rearrangement via homologous recombination, and we have applied these mice in studies of both low dose radiation and space radiation. In addition to more traditional approaches for assessing genomic stability, we have also explored radiation and possible beneficial effects (adaptive response), long term effects (persistent effects) and effects on communication among cells (bystander effects), both in vitro and in vivo. In terms of the adaptive response, we have not observed any significant induction of an adaptive response following long term low dose radiation in vivo, delivered at 300X background. In terms of persistent and bystander effects, we have revealed evidence of a bystander effect in vivo and with researchers at and demonstrated for the first time the molecular mechanism by which cells “remember” radiation exposure. Understanding the underlying molecular mechanisms by which radiation can induce genomic instability is fundamental to our ability to assess the biological impact of low dose radiation. Finally, in a parallel set of studies we have explored the effects of heavy

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

    SciTech Connect

    Soehn, Matthias . E-mail: Matthias.Soehn@med.uni-tuebingen.de; Yan Di; Liang Jian; Meldolesi, Elisa; Vargas, Carlos; Alber, Markus

    2007-03-15

    Purpose: Accurate modeling of rectal complications based on dose-volume histogram (DVH) data are necessary to allow safe dose escalation in radiotherapy of prostate cancer. We applied different equivalent uniform dose (EUD)-based and dose-volume-based normal tissue complication probability (NTCP) models to rectal wall DVHs and follow-up data for 319 prostate cancer patients to identify the dosimetric factors most predictive for Grade {>=} 2 rectal bleeding. Methods and Materials: Data for 319 patients treated at the William Beaumont Hospital with three-dimensional conformal radiotherapy (3D-CRT) under an adaptive radiotherapy protocol were used for this study. The following models were considered: (1) Lyman model and (2) logit-formula with DVH reduced to generalized EUD (3) serial reconstruction unit (RU) model (4) Poisson-EUD model, and (5) mean dose- and (6) cutoff dose-logistic regression model. The parameters and their confidence intervals were determined using maximum likelihood estimation. Results: Of the patients, 51 (16.0%) showed Grade 2 or higher bleeding. As assessed qualitatively and quantitatively, the Lyman- and Logit-EUD, serial RU, and Poisson-EUD model fitted the data very well. Rectal wall mean dose did not correlate to Grade 2 or higher bleeding. For the cutoff dose model, the volume receiving > 73.7 Gy showed most significant correlation to bleeding. However, this model fitted the data more poorly than the EUD-based models. Conclusions: Our study clearly confirms a volume effect for late rectal bleeding. This can be described very well by the EUD-like models, of which the serial RU- and Poisson-EUD model can describe the data with only two parameters. Dose-volume-based cutoff-dose models performed wor0008.

  1. Poster — Thur Eve — 27: Flattening Filter Free VMAT Quality Assurance: Dose Rate Considerations for Detector Response

    SciTech Connect

    Viel, Francis; Duzenli, Cheryl; Camborde, Marie-Laure; Strgar, Vincent; Horwood, Ron; Atwal, Parmveer; Gete, Ermias; Karan, Tania

    2014-08-15

    Introduction: Radiation detector responses can be affected by dose rate. Due to higher dose per pulse and wider range of mu rates in FFF beams, detector responses should be characterized prior to implementation of QA protocols for FFF beams. During VMAT delivery, the MU rate may also vary dramatically within a treatment fraction. This study looks at the dose per pulse variation throughout a 3D volume for typical VMAT plans and the response characteristics for a variety of detectors, and makes recommendations on the design of QA protocols for FFF VMAT QA. Materials and Methods: Linac log file data and a simplified dose calculation algorithm are used to calculate dose per pulse for a variety of clinical VMAT plans, on a voxel by voxel basis, as a function of time in a cylindrical phantom. Diode and ion chamber array responses are characterized over the relevant range of dose per pulse and dose rate. Results: Dose per pulse ranges from <0.1 mGy/pulse to 1.5 mGy/pulse in a typical VMAT treatment delivery using the 10XFFF beam. Diode detector arrays demonstrate increased sensitivity to dose (+./− 3%) with increasing dose per pulse over this range. Ion chamber arrays demonstrate decreased sensitivity to dose (+/− 1%) with increasing dose rate over this range. Conclusions: QA protocols should be designed taking into consideration inherent changes in detector sensitivity with dose rate. Neglecting to account for changes in detector response with dose per pulse can lead to skewed QA results.

  2. Exploring the dose response of radiochromic dosimeters

    NASA Astrophysics Data System (ADS)

    Skyt, P. S.; Wahlstedt, I.; Yates, E. S.; Muren, L. P.; Petersen, J. B. B.; Balling, P.

    2013-06-01

    The aim of this study was to explore the dose response of a newly developed radio-chromic hydrogel dosimeter based on leuco malachite green dye in a gelatine matrix. The original dosimeter composition was first investigated in terms of dose response and dose-rate dependence. In addition, the initiating compounds producing chlorine radicals were substituted with compounds producing fluorine radicals, oxygen-centered radicals, carbon-centered radicals and bromine radicals. Also the surfactant was substituted by other compounds of different molecular size and charge. The original composition gave a dose response of 3.5·10-3 Gy-1cm-1 at 6 Gy/min with a dose rate dependence giving a 27 % increase when decreasing the dose rate to 1 Gy/min. None of the substituted initiating components contributed to an increase in dose response while only one surfactant increased the dose response slightly.

  3. Fetal dexamethasone exposure accelerates development of renal function: relationship to dose, cell differentiation and growth inhibition.

    PubMed

    Slotkin, T A; Seidler, F J; Kavlock, R J; Gray, J A

    1992-02-01

    Fetal exposure to high doses of glucocorticoids slows cellular development and impairs organ performance, in association with growth retardation. Nevertheless, low doses of glucocorticoids may enhance cell differentiation and accelerate specific functions. The current study examined this apparent paradox in the developing rat kidney, using doses of dexamethasone that span the threshold for growth impairment: 0.05 or 0.2 mg/kg given on gestational days 17, 18 and 19. At the lower dose, which did not significantly retard body growth, the postnatal development of tubular reabsorptive capabilities for sodium, potassium, osmotic particles, water and urea was accelerated. These effects were less notable at the higher dose, which caused initial body growth impairment. The selectivity toward promotion of tubular function was evidenced by the absence of effect of either dose of dexamethasone on development of glomerular filtration rate. Because of the wide spectrum of dexamethasone's effects on tubular function, we also assessed fetal kidney adenylate cyclase as a means of detecting altered cell differentiation in the prenatal period during which dexamethasone was given. Either glucocorticoid dose increased the total adenylate cyclase catalytic activity (assessed with forskolin). Thus, the net effect of fetal dexamethasone exposure on development of renal excretory capabilities probably represents the summation of promoted cell differentiation and slowed development consequent to growth retardation. At low dose levels, the former effect predominates, leading to enhanced functional development, whereas higher doses that interfere with general growth and development can offset the direct promotional effect.

  4. Pediatric patient and staff dose measurements in barium meal fluoroscopic procedures

    NASA Astrophysics Data System (ADS)

    Filipov, D.; Schelin, H. R.; Denyak, V.; Paschuk, S. A.; Porto, L. E.; Ledesma, J. A.; Nascimento, E. X.; Legnani, A.; Andrade, M. E. A.; Khoury, H. J.

    2015-11-01

    This study investigates patient and staff dose measurements in pediatric barium meal series fluoroscopic procedures. It aims to analyze radiographic techniques, measure the air kerma-area product (PKA), and estimate the staff's eye lens, thyroid and hands equivalent doses. The procedures of 41 patients were studied, and PKA values were calculated using LiF:Mg,Ti thermoluminescent dosimeters (TLDs) positioned at the center of the patient's upper chest. Furthermore, LiF:Mg,Cu,P TLDs were used to estimate the equivalent doses. The results showed a discrepancy in the radiographic techniques when compared to the European Commission recommendations. Half of the results of the analyzed literature presented lower PKA and dose reference level values than the present study. The staff's equivalent doses strongly depends on the distance from the beam. A 55-cm distance can be considered satisfactory. However, a distance decrease of ~20% leads to, at least, two times higher equivalent doses. For eye lenses this dose is significantly greater than the annual limit set by the International Commission on Radiological Protection. In addition, the occupational doses were found to be much higher than in the literature. Changing the used radiographic techniques to the ones recommended by the European Communities, it is expected to achieve lower PKA values ​​and occupational doses.

  5. Antimicrobial Dose in Obese Patient

    PubMed Central

    Kassab, Sawsan; Syed Sulaiman, Syed Azhar; Abdul Aziz, Noorizan

    2007-01-01

    Introduction Obesity is a chronic disease that has become one of major public health issue in Malaysia because of its association with other disease states including cardiovascular disease and diabetes. Despite continuous efforts to educate the public about the health risks associated with obesity, prevalence of the disease continues to increase. Dosing of many medications are based on weight, limited data are available on how antimicrobial agents should be dosed in obesity. The aim of this case presentation is to discuss dose of antibiotic in obese patient. Case report: Patient: GMN, Malay, Female, 45 year old, 150kg, transferred from medical ward to ICU with problems of fever, orthopnea, sepsis secondary to nosocomial pneumonia. She was admitted to hospital a week ago for SOB on exertion, cyanosis, mildly dyspneic, somasthenia, bilateral ankle swelling. There was no fever, cough, chest pain, clubbing, flapping tremor. Her grand father has pre-morbid history of obesity, HPT, DM and asthma. She was non alcoholic, smoker, and not on diet control. The diagnosis Pickwickian syndrome was made. Patient was treated with IV Dopamine 11mcg/kg/min, IV Morphine 4mg/h. IV GTN 15mcg/min, IV Ca gluconate 10g/24h for 3/7, IV Zantac 50mg tds, IV Augmentin 1.2g tds, IV Lasix 40mg od, IV Plasil 10mg tds, S.c heparin 5000IU bd. patient become stable and moved to medical ward to continue her treatment. Discussion: The altered physiologic function seen in obese patients is a concern in patients receiving antimicrobial agents because therapeutic outcomes depend on achieving a minimum inhibitory concentration (MIC). The therapeutic effect of any drug can be altered when any of the 4 pharmacokinetic processes (absorption, distribution, metabolism, or elimination) are altered. Decreased blood flow rates and increased renal clearance in obese patients can affect drug distribution and elimination. Changes in serum protein levels can change the metabolism and distribution of drugs that are

  6. Oligodendroglial response to ionizing radiation: Dose and dose-rate response

    SciTech Connect

    Levy, R.P.

    1991-01-01

    An in vitro system using neuroglia from neonatal rat brain was developed to examining the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute [gamma]-radiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DIC 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. It was concluded that oligodendrocytes in irradiated cultures had significantly lower functional capacity than did unirradiated controls. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. At DIC 14, the group irradiated in a single fraction had significantly lower oligodendrocyte counts than any group given split doses; all irradiated cultures had marked depression of MBP synthesis, but to significant differences referable to time interval between doses. At DIC 21, cultures irradiated at intervals of 0 h to 2 h had similar oligodendrocyte counts to one another, but these counts were significantly lower than in cultures irradiated at intervals of 4 h to 6 h; MBP levels remained depressed at DIC 21 for all irradiated cultures. The oligodendrocyte response to dose rate (0.03 to 1.97 Gy/min) was evaluated at DIC 14 and DIC 21. Exposure at 0.03 Gy/min suppressed oligodendrocyte counts at DIC 21 less than did higher dose rates in 5-Gy irradiated cultures.

  7. Hanford Environmental Dose Reconstruction Project. Monthly report

    SciTech Connect

    Finch, S.M.; McMakin, A.H.

    1992-04-01

    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.

  8. Hanford Environmental Dose Reconstruction Project Monthly Report

    SciTech Connect

    Finch, S.M.; McMakin, A.H.

    1992-03-01

    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. Monthly report

    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.

  10. Multiple anatomy optimization of accumulated dose

    SciTech Connect

    Watkins, W. Tyler Siebers, Jeffrey V.; Moore, Joseph A.; Gordon, James; Hugo, Geoffrey D.

    2014-11-01

    Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dose variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated.

  11. Radiation dose measurements in coronary CT angiography

    PubMed Central

    Sabarudin, Akmal; Sun, Zhonghua

    2013-01-01

    Coronary computed tomography (CT) angiography is associated with high radiation dose and this has raised serious concerns in the literature. Awareness of various parameters for dose estimates and measurements of coronary CT angiography plays an important role in increasing our understanding of the radiation exposure to patients, thus, contributing to the implementation of dose-saving strategies. This article provides an overview of the radiation dose quantity and its measurement during coronary CT angiography procedures. PMID:24392190

  12. Multiple anatomy optimization of accumulated dose

    PubMed Central

    Watkins, W. Tyler; Moore, Joseph A.; Gordon, James; Hugo, Geoffrey D.; Siebers, Jeffrey V.

    2014-01-01

    Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dose variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated. PMID:25370619

  13. Hanford Environmental Dose Reconstruction Project. Monthly report

    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.

  14. Impact of Including Higher Actinides in Fast Reactor Transmutation Analyses

    SciTech Connect

    B. Forget; M. Asgari; R. Ferrer; S. Bays

    2007-09-01

    Previous fast reactor transmutation studies generally disregarded higher mass minor actinides beyond Cm-246 due to various considerations including deficiencies in nuclear cross-section data. Although omission of these higher mass actinides does not significantly impact the neutronic calculations and fuel cycle performance parameters follow-on neutron dose calculations related to fuel recycling, transportation and handling are significantly impacted. This report shows that including the minor actinides in the equilibrium fast reactor calculations will increase the predicted neutron emission by about 30%. In addition a sensitivity study was initiated by comparing the impact of different cross-section evaluation file for representing these minor actinides.

  15. The Toxicity and Benefit of Various Dosing Strategies for Interleukin-2 in Metastatic Melanoma and Renal Cell Carcinoma.

    PubMed

    Pachella, Laura A; Madsen, Lydia T; Dains, Joyce E

    2015-01-01

    Interleukin-2 (IL-2) therapy has been used with success in curing meta-static renal cell carcinoma and melanoma in a small minority of patients. However, the benefits can be accompanied by severe toxicity. This review of the literature discusses varying doses of IL-2 and their associated re-sponse rates and the toxicities associated with treatment. The review also explores the maximally beneficial dose with the most tolerable side effects. Although the higher-dose regimens with a more frequent dosing schedule produce higher-grade toxicity, they were found to deliver the most durable and complete responses. It is recommended to use a higher-dose regimen (720,000 IU/kg every 8 hours for a maximum of 15 doses) and provide sup-portive care for toxicity, so patients can have maximal benefit from therapy. PMID:26557408

  16. Higher Education Accounting Manual. Utah Coordinating Council of Higher Education.

    ERIC Educational Resources Information Center

    Utah State Coordinating Council of Higher Education, Salt Lake City.

    Recognition of a critical need for accurate and detailed information to refine the process of budgeting funds for higher education in Utah led to the preparation of this accounting manual for universities and colleges in the state. The manual presents guidelines for the uniform accounting and reporting of financial and statistical data, and is…

  17. The Hesburgh Papers: Higher Values in Higher Education.

    ERIC Educational Resources Information Center

    Hesburgh, Theodore M.

    In this book the president of Notre Dame University responds to the critics who see the teaching of religion and values as a hindrance to institutions of higher learning, suggesting that no university is truly a university unless it is universal and moves every scholar to look to the total universe. The significance of values in education is…

  18. Dose Escalated Liver Stereotactic Body Radiation Therapy at the Mean Respiratory Position

    SciTech Connect

    Velec, Michael; Moseley, Joanne L.; Dawson, Laura A.; Brock, Kristy K.

    2014-08-01

    Purpose: The dosimetric impact of dose probability based planning target volume (PTV) margins for liver cancer patients receiving stereotactic body radiation therapy (SBRT) was compared with standard PTV based on the internal target volume (ITV). Plan robustness was evaluated by accumulating the treatment dose to ensure delivery of the intended plan. Methods and Materials: Twenty patients planned on exhale CT for 27 to 50 Gy in 6 fractions using an ITV-based PTV and treated free-breathing were retrospectively evaluated. Isotoxic, dose escalated plans were created on midposition computed tomography (CT), representing the mean breathing position, using a dose probability PTV. The delivered doses were accumulated using biomechanical deformable registration of the daily cone beam CT based on liver targeting at the exhale or mean breathing position, for the exhale and midposition CT plans, respectively. Results: The dose probability PTVs were on average 38% smaller than the ITV-based PTV, enabling an average ± standard deviation increase in the planned dose to 95% of the PTV of 4.0 ± 2.8 Gy (9 ± 5%) on the midposition CT (P<.01). For both plans, the delivered minimum gross tumor volume (GTV) doses were greater than the planned nominal prescribed dose in all 20 patients and greater than the planned dose to 95% of the PTV in 18 (90%) patients. Nine patients (45%) had 1 or more GTVs with a delivered minimum dose more than 5 Gy higher with the midposition CT plan using dose probability PTV, compared with the delivered dose with the exhale CT plan using ITV-based PTV. Conclusions: For isotoxic liver SBRT planned and delivered at the mean respiratory, reduced dose probability PTV enables a mean escalation of 4 Gy (9%) in 6 fractions over ITV-based PTV. This may potentially improve local control without increasing the risk of tumor underdosing.

  19. On voxel-by-voxel accumulated dose for prostate radiation therapy using deformable image registration

    PubMed Central

    Yu, Jialu; Hardcastle, Nicholas; Jeong, Kyoungkeun; Bender, Edward T.; Ritter, Mark A.; Tomé, Wolfgang A.

    2015-01-01

    Since delivered dose is rarely the same with planned, we calculated the delivered total dose to ten prostate radiotherapy patients treated with rectal balloons using deformable dose accumulation (DDA) and compared it with the planned dose. The patients were treated with TomoTherapy using two rectal balloon designs: five patients had the Radiadyne balloon (balloon A), and five patients had the EZ-EM balloon (balloon B). Prostate and rectal wall contours were outlined on each pre-treatment MVCT for all patients. Delivered fractional doses were calculated using the MVCT taken immediately prior to delivery. Dose grids were accumulated to the last MVCT using DDA tools in Pinnacle3 ™ (v9.100, Philips Radiation Oncology Systems, Fitchburg, USA). Delivered total doses were compared with planned doses using prostate and rectal wall DVHs. The rectal NTCP was calculated based on total delivered and planned doses for all patients using the Lyman model. For 8/10 patients, the rectal wall NTCP calculated using the delivered total dose was less than planned, with seven patients showing a decrease of more than 5% in NTCP. For 2/10 patients studied, the rectal wall NTCP calculated using total delivered dose was 2% higher than planned. This study indicates that for patients receiving hypofractionated radiotherapy for prostate cancer with a rectal balloon, total delivered doses to prostate is similar with planned while delivered dose to rectal walls may be significantly different from planned doses. 8/10 patients show significant correlation between rectal balloon anterior-posterior positions and some VD values. PMID:24354754

  20. Estimation of immunization providers' activities cost, medication cost, and immunization dose errors cost in Iraq.

    PubMed

    Al-lela, Omer Qutaiba B; Bahari, Mohd Baidi; Al-abbassi, Mustafa G; Salih, Muhannad R M; Basher, Amena Y

    2012-06-01

    The immunization status of children is improved by interventions that increase community demand for compulsory and non-compulsory vaccines, one of the most important interventions related to immunization providers. The aim of this study is to evaluate the activities of immunization providers in terms of activities time and cost, to calculate the immunization doses cost, and to determine the immunization dose errors cost. Time-motion and cost analysis study design was used. Five public health clinics in Mosul-Iraq participated in the study. Fifty (50) vaccine doses were required to estimate activities time and cost. Micro-costing method was used; time and cost data were collected for each immunization-related activity performed by the clinic staff. A stopwatch was used to measure the duration of activity interactions between the parents and clinic staff. The immunization service cost was calculated by multiplying the average salary/min by activity time per minute. 528 immunization cards of Iraqi children were scanned to determine the number and the cost of immunization doses errors (extraimmunization doses and invalid doses). The average time for child registration was 6.7 min per each immunization dose, and the physician spent more than 10 min per dose. Nurses needed more than 5 min to complete child vaccination. The total cost of immunization activities was 1.67 US$ per each immunization dose. Measles vaccine (fifth dose) has a lower price (0.42 US$) than all other immunization doses. The cost of a total of 288 invalid doses was 744.55 US$ and the cost of a total of 195 extra immunization doses was 503.85 US$. The time spent on physicians' activities was longer than that spent on registrars' and nurses' activities. Physician total cost was higher than registrar cost and nurse cost. The total immunization cost will increase by about 13.3% owing to dose errors.

  1. Analysis of Dose Distribution in the Heart for Radiosurgical Ablation of Atrial Fibrillation

    PubMed Central

    Weidlich, Georg A.

    2016-01-01

    In a treatment planning study, radiosurgical treatment plans designed to produce lesions on the left atrium were created using two different methodologies. In one, structures in the heart (mitral valve and coronary arteries) were designated as critical structures while this was not done in the second plan. The treatment plans that were created were compared with standards for heart dose used when treating spine tumors. Although the dosage for the whole heart greatly exceeded the dose standards, when only the dose to the ventricles was considered, the plan where the mitral valve was spared was very close to the dose standards. The ventricles received a substantially higher dose in the plan where the mitral valve was not a critical structure. Although neither treatment plan was delivered, this study demonstrated the feasibility of treating the heart while minimizing dose to the ventricles. PMID:27610282

  2. Absorbed dose rate in air in metropolitan Tokyo before the Fukushima Daiichi Nuclear Power Plant accident.

    PubMed

    Inoue, K; Hosoda, M; Fukushi, M; Furukawa, M; Tokonami, S

    2015-11-01

    The monitoring of absorbed dose rate in air has been carried out continually at various locations in metropolitan Tokyo after the accident of the Fukushima Daiichi Nuclear Power Plant. While the data obtained before the accident are needed to more accurately assess the effects of radionuclide contamination from the accident, detailed data for metropolitan Tokyo obtained before the accident have not been reported. A car-borne survey of the absorbed dose rate in air in metropolitan Tokyo was carried out during August to September 2003. The average absorbed dose rate in air in metropolitan Tokyo was 49±6 nGy h(-1). The absorbed dose rate in air in western Tokyo was higher compared with that in central Tokyo. Here, if the absorbed dose rate indoors in Tokyo is equivalent to that outdoors, the annual effective dose would be calculated as 0.32 mSv y(-1).

  3. Analysis of Dose Distribution in the Heart for Radiosurgical Ablation of Atrial Fibrillation.

    PubMed

    Gardner, Edward A; Weidlich, Georg A

    2016-01-01

    In a treatment planning study, radiosurgical treatment plans designed to produce lesions on the left atrium were created using two different methodologies. In one, structures in the heart (mitral valve and coronary arteries) were designated as critical structures while this was not done in the second plan. The treatment plans that were created were compared with standards for heart dose used when treating spine tumors. Although the dosage for the whole heart greatly exceeded the dose standards, when only the dose to the ventricles was considered, the plan where the mitral valve was spared was very close to the dose standards. The ventricles received a substantially higher dose in the plan where the mitral valve was not a critical structure. Although neither treatment plan was delivered, this study demonstrated the feasibility of treating the heart while minimizing dose to the ventricles. PMID:27610282

  4. Changes in ambient dose equivalent rates around roads at Kawamata town after the Fukushima accident.

    PubMed

    Kinase, Sakae; Sato, Satoshi; Sakamoto, Ryuichi; Yamamoto, Hideaki; Saito, Kimiaki

    2015-11-01

    Changes in ambient dose equivalent rates noted through vehicle-borne surveys have elucidated ecological half-lives of radioactive caesium in the environment. To confirm that the ecological half-lives are appropriate for predicting ambient dose equivalent rates within living areas, it is important to ascertain ambient dose equivalent rates on/around roads. In this study, radiation monitoring on/around roads at Kawamata town, located about 37 km northwest of the Fukushima Daiichi Nuclear Power Plant, was performed using monitoring vehicles and survey meters. It was found that the ambient dose equivalent rates around roads were higher than those on roads as of October 2012. And withal the ecological half-lives on roads were essentially consistent with those around roads. With dose predictions using ecological half-lives on roads, it is necessary to make corrections to ambient dose equivalent rates through the vehicle-borne surveys against those within living areas. PMID:25953794

  5. Absorbed dose rate in air in metropolitan Tokyo before the Fukushima Daiichi Nuclear Power Plant accident.

    PubMed

    Inoue, K; Hosoda, M; Fukushi, M; Furukawa, M; Tokonami, S

    2015-11-01

    The monitoring of absorbed dose rate in air has been carried out continually at various locations in metropolitan Tokyo after the accident of the Fukushima Daiichi Nuclear Power Plant. While the data obtained before the accident are needed to more accurately assess the effects of radionuclide contamination from the accident, detailed data for metropolitan Tokyo obtained before the accident have not been reported. A car-borne survey of the absorbed dose rate in air in metropolitan Tokyo was carried out during August to September 2003. The average absorbed dose rate in air in metropolitan Tokyo was 49±6 nGy h(-1). The absorbed dose rate in air in western Tokyo was higher compared with that in central Tokyo. Here, if the absorbed dose rate indoors in Tokyo is equivalent to that outdoors, the annual effective dose would be calculated as 0.32 mSv y(-1). PMID:25944962

  6. Analysis of Dose Distribution in the Heart for Radiosurgical Ablation of Atrial Fibrillation

    PubMed Central

    Weidlich, Georg A.

    2016-01-01

    In a treatment planning study, radiosurgical treatment plans designed to produce lesions on the left atrium were created using two different methodologies. In one, structures in the heart (mitral valve and coronary arteries) were designated as critical structures while this was not done in the second plan. The treatment plans that were created were compared with standards for heart dose used when treating spine tumors. Although the dosage for the whole heart greatly exceeded the dose standards, when only the dose to the ventricles was considered, the plan where the mitral valve was spared was very close to the dose standards. The ventricles received a substantially higher dose in the plan where the mitral valve was not a critical structure. Although neither treatment plan was delivered, this study demonstrated the feasibility of treating the heart while minimizing dose to the ventricles.

  7. Higher education and civic engagement.

    PubMed

    Egerton, Muriel

    2002-12-01

    This paper focuses on the relationship between social engagement, particularly civic engagement, and education. It is well known that more highly educated people are more likely to engage in voluntary work in formalized settings. It has been difficult to disentangle the effect of higher education from that of family origin and occupational socialization. This paper examines the effects of tertiary education on the social and civic engagement of young people, using the British Household Panel Study. The social and civic activity of young people is observed in their late teens, before entering the labour market or tertiary education, and compared with that of the same young people in their early 20s, after completing tertiary education courses or gaining labour market experience. It was found that the social and civic engagement of young people who would enter higher education was higher in their late teens than that of their peers who did not enter. However, higher education had a small additional effect on civic engagement, for both young and mature students. The children of professionals were the social grouping most likely to be involved in civic activities. The relationship of higher education, professional occupations and family socialization is discussed.

  8. A dose monitoring system for dental radiography

    PubMed Central

    Lee, Chena; Kim, Jo-Eun; Symkhampha, Khanthaly; Lee, Woo-Jin; Huh, Kyung-Hoe; Yi, Won-Jin; Heo, Min-Suk; Choi, Soon-Chul; Yeom, Heon-Young

    2016-01-01

    Purpose The current study investigates the feasibility of a platform for a nationwide dose monitoring system for dental radiography. The essential elements for an unerring system are also assessed. Materials and Methods An intraoral radiographic machine with 14 X-ray generators and five sensors, 45 panoramic radiographic machines, and 23 cone-beam computed tomography (CBCT) models used in Korean dental clinics were surveyed to investigate the type of dose report. A main server for storing the dose data from each radiographic machine was prepared. The dose report transfer pathways from the radiographic machine to the main sever were constructed. An effective dose calculation method was created based on the machine specifications and the exposure parameters of three intraoral radiographic machines, five panoramic radiographic machines, and four CBCTs. A viewing system was developed for both dentists and patients to view the calculated effective dose. Each procedure and the main server were integrated into one system. Results The dose data from each type of radiographic machine was successfully transferred to the main server and converted into an effective dose. The effective dose stored in the main server is automatically connected to a viewing program for dentist and patient access. Conclusion A patient radiation dose monitoring system is feasible for dental clinics. Future research in cooperation with clinicians, industry, and radiologists is needed to ensure format convertibility for an efficient dose monitoring system to monitor unexpected radiation dose. PMID:27358817

  9. Chemical Dosing and First-Order Kinetics

    ERIC Educational Resources Information Center

    Hladky, Paul W.

    2011-01-01

    College students encounter a variety of first-order phenomena in their mathematics and science courses. Introductory chemistry textbooks that discuss first-order processes, usually in conjunction with chemical kinetics or radioactive decay, stop at single, discrete dose events. Although single-dose situations are important, multiple-dose events,…

  10. High-dose chromium(III) supplementation has no effects on body mass and composition while altering plasma hormone and triglycerides concentrations.

    PubMed

    Bennett, Randall; Adams, Bobbi; French, Amanda; Neggers, Yasmin; Vincent, John B

    2006-10-01

    Chromium is generally believed to be an essential element and is often claimed to have value as a weight loss or muscle building agent. Recent studies in humans and rats have failed to demonstrate effects on body composition, although recent studies with pharmacological doses of the cation [Cr(III)3O(O2CCH2CH3)6(H2O)3]+ (or Cr3) (< or =1 mg Cr/kg body mass) in rats have noted a trend toward body mass loss and fat mass loss. Thus, the effects of large gavage doses of Cr3 (1-10 mg Cr/kg) on body mass, organ mass, food intake, and blood plasma variables (insulin, glucose, leptin, cholesterol, and triglycerides) were examined over a 10-wk period using male Sprague-Dawley rats. No effects on body composition were noted, although Cr3 administration lowered (p < 0.05) plasma insulin, leptin, and triglycerides concentrations. As Cr3 is absorbed greater than 10-fold better than commercially available nutritional supplements, the lack of an effect of the Cr(III) compound at these levels of administration clearly indicates that Cr(III) supplements do not have an effect on body composition at any reasonable dosage.

  11. High-dose chromium(III) supplementation has no effects on body mass and composition while altering plasma hormone and triglycerides concentrations.

    PubMed

    Bennett, Randall; Adams, Bobbi; French, Amanda; Neggers, Yasmin; Vincent, John B

    2006-10-01

    Chromium is generally believed to be an essential element and is often claimed to have value as a weight loss or muscle building agent. Recent studies in humans and rats have failed to demonstrate effects on body composition, although recent studies with pharmacological doses of the cation [Cr(III)3O(O2CCH2CH3)6(H2O)3]+ (or Cr3) (< or =1 mg Cr/kg body mass) in rats have noted a trend toward body mass loss and fat mass loss. Thus, the effects of large gavage doses of Cr3 (1-10 mg Cr/kg) on body mass, organ mass, food intake, and blood plasma variables (insulin, glucose, leptin, cholesterol, and triglycerides) were examined over a 10-wk period using male Sprague-Dawley rats. No effects on body composition were noted, although Cr3 administration lowered (p < 0.05) plasma insulin, leptin, and triglycerides concentrations. As Cr3 is absorbed greater than 10-fold better than commercially available nutritional supplements, the lack of an effect of the Cr(III) compound at these levels of administration clearly indicates that Cr(III) supplements do not have an effect on body composition at any reasonable dosage. PMID:17114815

  12. Diagnostic Accuracy of CT Enterography for Active Inflammatory Terminal Ileal Crohn Disease: Comparison of Full-Dose and Half-Dose Images Reconstructed with FBP and Half-Dose Images with SAFIRE.

    PubMed

    Gandhi, Namita S; Baker, Mark E; Goenka, Ajit H; Bullen, Jennifer A; Obuchowski, Nancy A; Remer, Erick M; Coppa, Christopher P; Einstein, David; Feldman, Myra K; Kanmaniraja, Devaraju; Purysko, Andrei S; Vahdat, Noushin; Primak, Andrew N; Karim, Wadih; Herts, Brian R

    2016-08-01

    Purpose To compare the diagnostic accuracy and image quality of computed tomographic (CT) enterographic images obtained at half dose and reconstructed with filtered back projection (FBP) and sinogram-affirmed iterative reconstruction (SAFIRE) with those of full-dose CT enterographic images reconstructed with FBP for active inflammatory terminal or neoterminal ileal Crohn disease. Materials and Methods This retrospective study was compliant with HIPAA and approved by the institutional review board. The requirement to obtain informed consent was waived. Ninety subjects (45 with active terminal ileal Crohn disease and 45 without Crohn disease) underwent CT enterography with a dual-source CT unit. The reference standard for confirmation of active Crohn disease was active terminal ileal Crohn disease based on ileocolonoscopy or established Crohn disease and imaging features of active terminal ileal Crohn disease. Data from both tubes were reconstructed with FBP (100% exposure); data from the primary tube (50% exposure) were reconstructed with FBP and SAFIRE strengths 3 and 4, yielding four datasets per CT enterographic examination. The mean volume CT dose index (CTDIvol) and size-specific dose estimate (SSDE) at full dose were 13.1 mGy (median, 7.36 mGy) and 15.9 mGy (median, 13.06 mGy), respectively, and those at half dose were 6.55 mGy (median, 3.68 mGy) and 7.95 mGy (median, 6.5 mGy). Images were subjectively evaluated by eight radiologists for quality and diagnostic confidence for Crohn disease. Areas under the receiver operating characteristic curves (AUCs) were estimated, and the multireader, multicase analysis of variance method was used to compare reconstruction methods on the basis of a noninferiority margin of 0.05. Results The mean AUCs with half-dose scans (FBP, 0.908; SAFIRE 3, 0.935; SAFIRE 4, 0.924) were noninferior to the mean AUC with full-dose FBP scans (0.908; P < .003). The proportion of images with inferior quality was significantly higher with all

  13. Approximate distribution of dose among foetal organs for radioiodine uptake via placenta transfer

    NASA Astrophysics Data System (ADS)

    Millard, R. K.; Saunders, M.; Palmer, A. M.; Preece, A. W.

    2001-11-01

    Absorbed radiation doses to internal foetal organs were calculated according to the medical internal radiation dose (MIRD) technique in this study. Anthropomorphic phantoms of the pregnant female as in MIRDOSE3 enabled estimation of absorbed dose to the whole foetus at two stages of gestation. Some foetal organ self-doses could have been estimated by invoking simple spherical models for thyroid, liver, etc, but we investigated the use of the MIRDOSE3 new-born phantom as a surrogate for the stage 3 foetus, scaled to be compatible with total foetal body mean absorbed dose/cumulated activity. We illustrate the method for obtaining approximate dose distribution in the foetus near term following intake of 1 MBq of 123I, 124I, 125I or 131I as sodium iodide by the mother using in vivo biodistribution data examples from a good model of placenta transfer. Doses to the foetal thyroid of up to 1.85 Gy MBq-1 were predicted from the 131I uptake data. Activity in the foetal thyroid was the largest contributor to absorbed dose in the foetal body, brain, heart and thymus. Average total doses to the whole foetus ranged from 0.16 to 1.2 mGy MBq-1 for stages 1 and 3 of pregnancy using the MIRDOSE3 program, and were considerably higher than those predicted from the maternal contributions alone. Doses to the foetal thymus and stomach were similar, around 2-3 mGy MBq-1. Some foetal organ doses from the radioiodides were ten times higher than to the corresponding organs of the mother, and up to 100 times higher to the thyroid. The fraction of activity uptakes in foetal organs were distributed similarly to the maternal ones.

  14. UGT genotyping in belinostat dosing.

    PubMed

    Goey, Andrew K L; Figg, William D

    2016-03-01

    Certain genetic polymorphisms of UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) can reduce gene expression (*28, *60, *93) or activity (*6), thereby altering the pharmacokinetics, pharmacodynamics, and the risk of toxicities of UGT1A1 substrates, of which irinotecan is a widely-described example. This review presents an overview of the clinical effects of UGT1A1 polymorphisms on the pharmacology of UGT1A1 substrates, with a special focus on the novel histone deacetylase inhibitor belinostat. Belinostat, approved for the treatment of peripheral T-cell lymphoma, is primarily glucuronidated by UGT1A1. Recent preclinical and clinical data showed that UGT1A1*28 was associated with reduced glucuronidation in human liver microsomes, while in a retrospective analysis of a Phase I trial with patients receiving belinostat UGT1A1*60 was predominantly associated with increased belinostat plasma concentrations. Furthermore, both UGT1A1*28 and *60 variants were associated with increased incidence of thrombocytopenia and neutropenia. Using population pharmacokinetic analysis a 33% dose reduction has been proposed for patients carrying UGT1A1 variant alleles. Clinical effects of this genotype-based dosing recommendation is currently prospectively being investigated. Overall, the data suggest that UGT1A1 genotyping is useful for improving belinostat therapy. PMID:26773202

  15. Wildlife toxicity extrapolations: Dose metric

    SciTech Connect

    Fairbrother, A.; Berg, M. van den

    1995-12-31

    Ecotoxicological assessments must rely on the extrapolation of toxicity data from a few indicator species to many species of concern. Data are available from laboratory studies (e.g., quail, mallards, rainbow trout, fathead minnow) and some planned or serendipitous field studies of a broader, but by no means comprehensive, suite of species. Yet all ecological risk assessments begin with an estimate of risk based on information gleaned from the literature. One is then confronted with the necessity of extrapolating toxicity information from a limited number of indicator species to all organisms of interest. This is a particularly acute problem when trying to estimate hazards to wildlife in terrestrial systems as there is an extreme paucity of data for most chemicals in all but a handful of species. This section continues the debate by six panelists of the ``correct`` approach for determining wildlife toxicity thresholds by examining which dose metric to use for threshold determination and interspecific extrapolation, Since wild animals are exposed to environmental contaminants primarily through ingestion, should threshold values be expressed as amount of chemical in the diet (e.g., ppm) or as a body weight-adjusted dose (mg/kg/day)? Which of these two approaches is most relevant for ecological risk assessment decision making? Which is best for interspecific extrapolations? Converting from one metric to the other can compound uncertainty if the actual consumption rates of a species is unknown. How should this be dealt with? Is it of sufficient magnitude to be of concern?

  16. Calculation of dose conversion factors for doses in the fingernails to organ doses at external gamma irradiation in air

    PubMed Central

    Khailov, A.M.; Ivannikov, A. I.; Skvortsov, V.G.; Stepanenko, V.F.; Orlenko, S.P.; Flood, A.B.; Williams, B.B.; Swartz, H.M.

    2015-01-01

    Absorbed doses to fingernails and organs were calculated for a set of homogenous external gamma-ray irradiation geometries in air. The doses were obtained by stochastic modeling of the ionizing particle transport (Monte Carlo method) for a mathematical human phantom with arms and hands placed loosely along the sides of the body. The resulting dose conversion factors for absorbed doses in fingernails can be used to assess the dose distribution and magnitude in practical dose reconstruction problems. For purposes of estimating dose in a large population exposed to radiation in order to triage people for treatment of acute radiation syndrome, the calculated data for a range of energies having a width of from 0.05 to 3.5 MeV were used to convert absorbed doses in fingernails to corresponding doses in organs and the whole body as well as the effective dose. Doses were assessed based on assumed rates of radioactive fallout at different time periods following a nuclear explosion. PMID:26347593

  17. The effect of decitabine dose modification and myelosuppression on response and survival in patients with myelodysplastic syndromes.

    PubMed

    Jabbour, Elias; Garcia-Manero, Guillermo; Cornelison, A Megan; Cortes, Jorge E; Ravandi, Farhad; Daver, Naval; Kadia, Tapan; Teng, Angela; Kantarjian, Hagop

    2015-02-01

    Myelosuppression in myelodysplastic syndromes (MDS) is associated with the hypomethylating agent decitabine. A retrospective pooled analysis of two decitabine clinical trials in patients with MDS conducted Cox regression analyses of red blood cell or platelet dependence, myelosuppression, dose modification, cycle delay or dose reduction, and survival effects. In 182 patients, baseline platelet dependence was a predictor for dose modification, reduction or delay, and death (modification: p=0.006, hazard ratio [HR]=2.04; reduction/delay: p=0.011, HR=2.00; death: p=0.003, HR=1.94). Patients with dose modifications had significantly higher overall response rates versus those with none (22% vs. 10%; p=0.015). Patients with no dose modifications had faster progression to acute myeloid leukemia (AML) versus patients with dose modifications (p=0.004). Without dose modifications, patients tended to drop out due to disease progression or other reasons. Decitabine dose modifications on treatment may indicate response to treatment.

  18. Application of a PAGAT/MgCl2 gel for dose measurements in a 150 MeV proton beam

    NASA Astrophysics Data System (ADS)

    Tominaga, T.; Hayashi, S.; Usui, S.; Kawamura, H.; Katahira, K.

    2013-06-01

    The purpose of this study is to evaluate the dose response of polyacrylamide-based gel (PAGAT) when irradiated with clinical proton beams. Recently inorganic salt additive in gel has been reported to improve dose sensitivity substantially. We attempted to add MgCl2 (0.5M) to regular PAGAT gel in order to compensate its lower radiation sensitivity. The spin-spin relaxation rates (R2) as dose readout was calculated from MR imaging after irradiation with 150MeV proton beam. The dose sensitivity was discussed from the slope at dose-R2 response curve. As the result, the sensitivity of the gel with MgCl2 is approximately 3 times higher than that of regular PAGAT gel without spoiling dose response stability under the various irradiation conditions such as dose rate and dose integration.

  19. Effect of tissue composition on dose distribution in brachytherapy with various photon emitting sources

    PubMed Central

    Ghorbani, Mahdi; Salahshour, Fateme; Haghparast, Abbas; Knaup, Courtney

    2014-01-01

    Purpose The aim of this study is to compare the dose in various soft tissues in brachytherapy with photon emitting sources. Material and methods 103Pd, 125I, 169Yb, 192Ir brachytherapy sources were simulated with MCNPX Monte Carlo code, and their dose rate constant and radial dose function were compared with the published data. A spherical phantom with 50 cm radius was simulated and the dose at various radial distances in adipose tissue, breast tissue, 4-component soft tissue, brain (grey/white matter), muscle (skeletal), lung tissue, blood (whole), 9-component soft tissue, and water were calculated. The absolute dose and relative dose difference with respect to 9-component soft tissue was obtained for various materials, sources, and distances. Results There was good agreement between the dosimetric parameters of the sources and the published data. Adipose tissue, breast tissue, 4-component soft tissue, and water showed the greatest difference in dose relative to the dose to the 9-component soft tissue. The other soft tissues showed lower dose differences. The dose difference was also higher for 103Pd source than for 125I, 169Yb, and 192Ir sources. Furthermore, greater distances from the source had higher relative dose differences and the effect can be justified due to the change in photon spectrum (softening or hardening) as photons traverse the phantom material. Conclusions The ignorance of soft tissue characteristics (density, composition, etc.) by treatment planning systems incorporates a significant error in dose delivery to the patient in brachytherapy with photon sources. The error depends on the type of soft tissue, brachytherapy source, as well as the distance from the source. PMID:24790623

  20. Pharmacokinetics of single ascending doses of the P-glycoprotein inhibitor tariquidar in healthy subjects

    PubMed Central

    Bauer, M.; Zeitlinger, M.; Todorut, D.; Böhmdorfer, M.; Müller, M.; Langer, O.; Jäger, W.

    2013-01-01

    We assessed the pharmacokinetics (PK), tolerability and safety of tariquidar (TQD), a P-glycoprotein (Pgp) inhibitor, after i.v. administration of single ascending doses. Employed doses were up to 4-fold higher than in previous clinical trials in cancer patients and are capable to inhibit Pgp at the blood-brain barrier (BBB). 15 male healthy volunteers were randomised to receive single i.v. doses of TQD at 4, 6 or 8 mg/kg body weight and underwent blood sampling over 24 h. TQD concentrations were determined in plasma samples with high-performance liquid chromatography-mass spectrometry. No dose limiting toxicities of TQD were observed. Area under the plasma concentration-time curve from start until 24 h after end of infusion (AUC0-n) was positively correlated with administered TQD dose (r=0.8981, p<0.0001). Moreover, we found a positive correlation for volume of distribution at steady state Vss (r=0.7129, p=0.0004) with TQD dose. Dose dependency of Vss points to non-linear PK of TQD, which was in all likelihood caused by transporter saturation at high TQD doses. Acceptable safety and tolerability and dose-linear increases in plasma exposure support future use of TQD at doses up to 8 mg/kg to inhibit Pgp at the human BBB. PMID:23146816

  1. Analysis of radiation doses from operation of postulated commercial spent fuel transportation systems: Main report

    SciTech Connect

    Schneider, K.J.; Hostick, C.J.; Ross, W.A.; Peterson, R.W.; Smith, R.I.; Stiles, D.L.; Daling, P.M.; Weakley, S.A.; Grinde, R.B.; Young, J.R.

    1987-11-01

    This report contains a system study of estimated radiation doses to the public and workers resulting from the transport of spent fuel from commercial nuclear power reactors to a geologic repository. The report contains a detailed breakdown of activities and a description of time/distance/dose-rate estimates for each activity within the system. Collective doses are estimated for each of the major activities at the reactor site, in transit, and at the repository receiving facility. Annual individual doses to the maximally exposed individuals or groups of individuals are also estimated. A total of 17 alternatives and subalternatives to the postulated reference transportation system are identified, conceptualized, and their dose-reduction potentials and costs estimated. Resulting ratios of ..delta..cost/..delta..collective system dose for each alternative relative to the postulated reference transportation system are given. Most of the alternatives evaluated are estimated to provide both cost and dose reductions. Major reductions in transportation system dose and cost are estimated to result from using higher-capacity rail and truck casks, and particularly when replacing legalweight truck casks with ''advanced design'' overweight truck casks. The greatest annual dose reduction to the highest exposed individual workers (i.e., at the repository) is estimated to be achieved by using remote handling equipment for the cask handling operations at the repository. Additional shielding is also effective in reducing doses to both radiation workers at the reactor and repository and to transport workers. 69 refs., 36 figs., 156 tabs.

  2. An evaluation of organ dose modulation on a GE optima CT660-computed tomography scanner.

    PubMed

    Dixon, Matthew T; Loader, Robert J; Stevens, Gregory C; Rowles, Nick P

    2016-01-01

    Organ Dose Modulation or ODM (GE Healthcare, Milwaukee, WI) was evaluated to characterize changes in CTDIvol, image noise, effective dose, and organ dose saving to patients. Three separate investigations were completed: a tube current modulation phantom was scanned with and without ODM, a CTDIvol phantom was scanned with ODM, and Monte Carlo simulations were performed. ODM was found to reduce the CTDIvol by approximately 20% whilst increasing the noise by approximately 14%. This was reflected in the dose distribution, where the anterior peripheral dose was reduced by approximately 40% whilst the identical poste-rior dose remained largely unaffected. Enabling ODM for the entire scan would reduce the effective dose by approximately 24%; however, this saving reduces to 5% if the images are matched for CTDIvol. These savings mostly originated from reductions in dose to the stomach, breasts, colon, bladder, and liver. ODM has the effect of a global reduction in CTDIvol with an associated increase in image noise. The benefit of ODM was found to be reduced when the dose-saving contribution from the reduced CTDIvol was removed. Given that there is a higher contribution to effective dose throughout the body from the anterior projections, consideration should be given to applying ODM throughout. PMID:27167255

  3. Determining the Lowest Optimally Effective Methotrexate Dose for Individual RA Patients Using Their Dose Response Relation in a Tight Control Treatment Approach

    PubMed Central

    Nair, Sandhya C.; Jacobs, Johannes W. G.; Bakker, Marije F.; Jahangier, Z. Nazira; Bijlsma, Johannes W. J.; van Laar, Jacobs M.; Lafeber, Floris P. J. G.; Welsing, Paco M. J.

    2016-01-01

    Objective To determine the optimal methotrexate dose in individual patients and to explore whether this optimal dose and the level of disease activity at that dose could be predicted. Methods Data from CAMERA II trial comparing MTX and MTX with 10 mg of prednisone both in a tight control treatment strategy in early RA was used. For each patient a curve for disease activity over time was fitted and the MTX dose after which further step-up did not result in relevant improvement in disease activity anymore was determined the 'lowest optimally effective MTX dose (LOED)'. The association of demographic and clinical characteristics at baseline with this LOED and with the level of disease activity reached at LOED was studied. Results In 204 (100 MTX and 104 MTX with prednisone) out of 236 patients LOED could be defined. 10 mg/wk was the most prevalent LOED in patients treated with MTX and prednisone and 10 mg/wk, 20 mg/wk and 30 mg/wk in the MTX strategy. Although the specific LOED could not reliably be predicted, higher baseline disease activity, height and lower weight were associated with higher LOEDs (i.e at least 15 mg/wk). A score was presented to decide on a starting dose of 10 mg/wk or (at least) 15 mg/wk. The level of disease activity at LOED could not be reliably predicted. Conclusion A starting dose of 10 mg/wk might be a good choice for most patients and is frequently already the optimal dose. However, a subgroup of patient can be determined who would require higher MTX doses. PMID:26987073

  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. A Program for Calculating Radiation Dose Rates.

    1986-01-27

    Version 00 SMART calculates radiation dose rate at the center of the outer cask surface. It can be applied to determine the radiation dose rate on each cask if source conditions, characteristic function, and material conditions in the bottle regions are given. MANYCASK calculates radiation dose rate distribution in a space surrounded by many casks. If the dose rate on each cask surface can be measured, MANYCASK can be applied to predict dose spatial dosemore » rate distribution for any case of cask configuration.« less

  6. Hanford Environmental Dose Reconstruction Project: Monthly Report

    SciTech Connect

    Finch, S.M.

    1990-07-01

    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 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, and Environmental Pathways and Dose Estimates. 3 figs.

  7. Profile of Pacific Higher Education.

    ERIC Educational Resources Information Center

    Research and Development Cadre, Honolulu, HI.

    Comparative data concerning institutions of higher education in the Pacific Islands are tabulated and summarized to aid in program planning, development, and implementation in that region. The jurisdictions covered are: American Samoa; Palau; the Northern Mariana Islands; Micronesia; Kosrae; Pohnpei; Truk; Yap; Guam; Hawaii; and the Marshall…

  8. Social Stratification in Higher Education

    ERIC Educational Resources Information Center

    Grodsky, Eric; Jackson, Erika

    2009-01-01

    Background/Context: Over the past half century, scholars in a variety of fields have contributed to our understanding of the relationship between higher education and social stratification. We review this literature, highlighting complementarities and inconsistencies. Purpose/Objective/Research Question/Focus of Study: We situate our review of the…

  9. Emerging Trends in Higher Education.

    ERIC Educational Resources Information Center

    Mayville, Zari

    This literature survey examines trends in higher education requiring a broad base of support from the changing institutions and the people who have to respond to, plan for, and manage the changes. Trends are identified in the areas of enrollment, financial aid, curricula, faculty, financial status, and assessment. Trends affecting enrollment…

  10. Gender Matters in Higher Education

    ERIC Educational Resources Information Center

    Harrop, Alex; Tattersall, Andy; Goody, Adam

    2007-01-01

    Much of the research in higher education has treated student bodies as homogeneous groups with a consequent neglect of any consideration of gender differences. To test the validity of such research a questionnaire was administered to 255 psychology students. The results showed some important differences in responses between the genders. In…

  11. Student Influence and Higher Education.

    ERIC Educational Resources Information Center

    Juola, Arvo E.

    Since 1965, student views and feelings have influenced great changes in higher education, sometimes to the detriment of long-term interests in academic institutions and colleges. One conspicuous recent trend is the desire of college students for more influence, impact, or power. Other prevalent attitudes may be characterized as a desire to be…

  12. Faculty Retention in Higher Education

    ERIC Educational Resources Information Center

    Soomro, Tariq Rahim; Ahmad, Reyaz

    2013-01-01

    Criteria for retaining or firing a highly qualified faculty in higher education in many cases are vague and unclear. This situation is neither a comfortable, nor a healthy, both for the faculty and the administration. Stakeholders have enough reason to blame each other in the absence of transparent mechanism. This paper proposes a transparent…

  13. Asian Americans and Higher Education.

    ERIC Educational Resources Information Center

    Endo, Russell

    1980-01-01

    Problems that Asian Americans face in higher education include poor communications skills; stress resulting from family and community pressure to achieve; and universities' reluctance to hire Asian American staff, recruit and provide financial support for Asian American students, and provide relevant curriculum. Various programs have begun to…

  14. The Battle for Higher Standards

    ERIC Educational Resources Information Center

    Luna, Tom; Rush, Mike; Gramer, Rod; Stewart, Roger

    2014-01-01

    To remain internationally competitive, states needed clearer, higher, and comparable K-12 learning standards aligned with college and career expectations, and as ambitious as those of the countries that lead the world in education. Idaho's old academic standards were not preparing students for postsecondary education, which contributed to the…

  15. Transnational Higher Education in Uzbekistan

    ERIC Educational Resources Information Center

    Sia, E. K.

    2014-01-01

    This paper provides an overview of transnational higher education (THE) in Uzbekistan. It includes a brief account of THE current and future market trends. The data, gathered from a literature search, show that the demand for THE (off-campus) is growing even faster than the demand for international (on-campus) programmes. This paper then provides…

  16. Higher Education and Regional Development.

    ERIC Educational Resources Information Center

    Neave, Guy

    1979-01-01

    The effect that the university has upon its region and the issue of regional control of higher education are examined. A definition of regional development is offered and regional planning, relevant research, cultural mobilization, and the Jacobin university are described. (Author/MLW)

  17. Today's Higher Education IT Workforce

    ERIC Educational Resources Information Center

    Bichsel, Jacqueline

    2014-01-01

    The professionals making up the current higher education IT workforce have been asked to adjust to a culture of increased IT consumerization, more sourcing options, broader interest in IT's transformative potential, and decreased resources. Disruptions that include the bring-your-own-everything era, cloud computing, new management practices,…

  18. Higher Ambitions Summit. Rapporteur Report

    ERIC Educational Resources Information Center

    Nash, Ian

    2014-01-01

    The Sutton Trust and Pearson two-day summit on higher ambitions in apprenticeships and vocational education drew more than 120 leaders in education, training and employment, policy makers, academics, and researchers to London. Delegates heard from political leaders stressing the importance they attach to high-quality apprenticeships. Presentations…

  19. Disability Discrimination in Higher Education.

    ERIC Educational Resources Information Center

    Weber, Mark C.

    2000-01-01

    Reviews court cases in 1999 related to disability discrimination in higher education focusing on the Americans with Disabilities Act and section 504 of the Rehabilitation Act of 1973. The "Garrett" case regarding Eleventh Amendment immunity is the case most likely to be significant in the development of the law of disability discrimination. (SLD)

  20. Disability Discrimination in Higher Education.

    ERIC Educational Resources Information Center

    Weber, Mark C.

    2002-01-01

    Reviews developments in 2000 in the law of disability discrimination as it relates to higher education, which falls into five categories: (1) definition of a qualified individual; (2) accommodations, access, undue burden, and fundamental alteration of programs; (3) intentional discrimination, harassment, and retaliation; (4) Eleventh Amendment…