ASCENDE-RT: An Analysis of Treatment-Related Morbidity for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost with a Dose-Escalated External Beam Boost for High- and Intermediate-Risk Prostate Cancer

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

Rodda, Sree; Tyldesley, Scott; Department of Surgery, University of British Columbia, Vancouver, British Columbia

Purpose: To report the genitourinary (GU) and gastrointestinal (GI) morbidity and erectile dysfunction in a randomized trial comparing 2 methods of dose escalation for high- and intermediate-risk prostate cancer. Methods and Materials: ASCENDE-RT (Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy) enrolled 398 men, median age 68 years, who were then randomized to either a standard arm that included 12 months of androgen deprivation therapy and pelvic irradiation to 46 Gy followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. At clinic visits, investigators recorded GUmore » and GI morbidity and information on urinary continence, catheter use, and erectile function. Exclusion of 15 who received nonprotocol treatment and correction of 14 crossover events left 195 men who actually received a DE-EBRT boost and 188, an LDR-PB boost. Median follow-up was 6.5 years. Results: The LDR-PB boost increased the risk of needing temporary catheterization and/or requiring incontinence pads. At 5 years the cumulative incidence of grade 3 GU events was 18.4% for LDR-PB, versus 5.2% for DE-EBRT (P<.001). Compared with the cumulative incidence, the 5-year prevalence of grade 3 GU morbidity was substantially lower for both arms (8.6% vs 2.2%, P=.058). The 5-year cumulative incidence of grade 3 GI events was 8.1% for LDR-PB, versus 3.2% for DE-EBRT (P=.124). The 5-year prevalence of grade 3 GI toxicity was lower than the cumulative incidence for both arms (1.0% vs 2.2%, respectively). Among men reporting adequate baseline erections, 45% of LDR-PB patients reported similar erectile function at 5 years, versus 37% after DE-EBRT (P=.30). Conclusions: The incidence of acute and late GU morbidity was higher after LDR-PB boost, and there was a nonsignificant trend for worse GI morbidity. No differences in the frequency of erectile dysfunction were observed.« less

The application of retrospective luminescence dosimetry in areas affected by fallout from the semipalatinsk nuclear test site: an evaluation of potential.

PubMed

Bailiff, I K; Stepanenko, V F; Göksu, H Y; Jungner, H; Balmukhanov, S B; Balmukhanov, T S; Khamidova, L G; Kisilev, V I; Kolyado, I B; Kolizshenkov, T V; Shoikhet, Y N; Tsyb, A F

2004-12-01

Luminescence retrospective dosimetry techniques have been applied with ceramic bricks to determine the cumulative external gamma dose due to fallout, primarily from the 1949 test, in populated regions lying NE of the Semipalatinsk Nuclear Test Site in Altai, Russia, and the Semipalatinsk region, Kazakhstan. As part of a pilot study, nine settlements were examined, three within the regions of highest predicted dose (Dolon in Kazakshstan; Laptev Log and Leshoz Topolinskiy in Russia) and the remainder of lower predicted dose (Akkol, Bolshaya Vladimrovka, Kanonerka, and Izvestka in Kazakshstan; Rubtsovsk and Kuria in Russia) within the lateral regions of the fallout trace due to the 1949 test. The settlement of Kainar, mainly affected by the 24 September 1951 nuclear test, was also examined. The bricks from this region were found to be generally suitable for use with the luminescence method. Estimates of cumulative absorbed dose in air due to fallout for Dolon and Kanonerka in Kazakshstan and Leshoz Topolinskiy were 475 +/- 110 mGy, 240 +/- 60 mGy, and 230 +/- 70 mGy, respectively. The result obtained in Dolon village is in agreement with published calculated estimates of dose normalized to Cs concentration in soil. At all the other locations (except Kainar) the experimental values of cumulative absorbed dose obtained indicated no significant dose due to fallout that could be detected within a margin of about 25 mGy. The results demonstrate the potential suitability of the luminescence method to map variations in cumulative dose within the relatively narrow corridor of fallout distribution from the 1949 test. Such work is needed to provide the basis for accurate dose reconstruction in settlements since the predominance of short-lived radionuclides in the fallout and a high degree of heterogeneity in the distribution of fallout are problematic for the application of conventional dosimetry techniques.

Leukemia risk associated with chronic external exposure to ionizing radiation in a French cohort of nuclear workers.

PubMed

Metz-Flamant, C; Samson, E; Caër-Lorho, S; Acker, A; Laurier, D

2012-11-01

Leukemia is one of the earliest cancer effects observed after acute exposure to relatively high doses of ionizing radiation. Leukemia mortality after external exposure at low doses and low-dose rates has been investigated at the French Atomic Energy Commission (CEA) and Nuclear Fuel Company (AREVA NC) after an additional follow-up of 10 years. The cohort included radiation-monitored workers employed for at least one year during 1950-1994 at CEA or AREVA NC and followed during 1968-2004. Association between external exposure and leukemia mortality was estimated with excess relative risk (ERR) models and time-dependent modifying factors were investigated with time windows. The cohort included 36,769 workers, followed for an average of 28 years, among whom 73 leukemia deaths occurred. Among the workers with a positive recorded dose, the mean cumulative external dose was 21.7 mSv. Results under a 2-year lag assumption suggested that the risk of leukemia (except chronic lymphatic leukemia) increased significantly by 8% per 10 mSv. The magnitude of the association for myeloid leukemia was larger. The higher ERR/Sv for doses received 2-14 years earlier suggest that time since exposure modifies the effect. The ERR/Sv also appeared higher for doses received at exposure rates ≥20 mSv per year. These results are consistent with those found in other studies of nuclear workers. However, confidence intervals are still wide. Further analyses should be conducted in pooled cohorts of nuclear workers.

Semimechanistic Bone Marrow Exhaustion Pharmacokinetic/Pharmacodynamic Model for Chemotherapy-Induced Cumulative Neutropenia.

PubMed

Henrich, Andrea; Joerger, Markus; Kraff, Stefanie; Jaehde, Ulrich; Huisinga, Wilhelm; Kloft, Charlotte; Parra-Guillen, Zinnia Patricia

2017-08-01

Paclitaxel is a commonly used cytotoxic anticancer drug with potentially life-threatening toxicity at therapeutic doses and high interindividual pharmacokinetic variability. Thus, drug and effect monitoring is indicated to control dose-limiting neutropenia. Joerger et al. (2016) developed a dose individualization algorithm based on a pharmacokinetic (PK)/pharmacodynamic (PD) model describing paclitaxel and neutrophil concentrations. Furthermore, the algorithm was prospectively compared in a clinical trial against standard dosing (Central European Society for Anticancer Drug Research Study of Paclitaxel Therapeutic Drug Monitoring; 365 patients, 720 cycles) but did not substantially improve neutropenia. This might be caused by misspecifications in the PK/PD model underlying the algorithm, especially without consideration of the observed cumulative pattern of neutropenia or the platinum-based combination therapy, both impacting neutropenia. This work aimed to externally evaluate the original PK/PD model for potential misspecifications and to refine the PK/PD model while considering the cumulative neutropenia pattern and the combination therapy. An underprediction was observed for the PK (658 samples), the PK parameters, and these parameters were re-estimated using the original estimates as prior information. Neutrophil concentrations (3274 samples) were overpredicted by the PK/PD model, especially for later treatment cycles when the cumulative pattern aggravated neutropenia. Three different modeling approaches (two from the literature and one newly developed) were investigated. The newly developed model, which implemented the bone marrow hypothesis semiphysiologically, was superior. This model further included an additive effect for toxicity of carboplatin combination therapy. Overall, a physiologically plausible PK/PD model was developed that can be used for dose adaptation simulations and prospective studies to further improve paclitaxel/carboplatin combination therapy. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

L-Boronophenylalanine-Mediated Boron Neutron Capture Therapy for Malignant Glioma Progressing After External Beam Radiation Therapy: A Phase I Study

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

Kankaanranta, Leena; Seppaelae, Tiina; Koivunoro, Hanna

Purpose: To investigate the safety of boronophenylalanine-mediated boron neutron capture therapy (BNCT) in the treatment of malignant gliomas that progress after surgery and conventional external beam radiation therapy. Methods and Materials: Adult patients who had histologically confirmed malignant glioma that had progressed after surgery and external beam radiotherapy were eligible for this Phase I study, provided that >6 months had elapsed from the last date of radiation therapy. The first 10 patients received a fixed dose, 290 mg/kg, of L-boronophenylalanine-fructose (L-BPA-F) as a 2-hour infusion before neutron irradiation, and the remaining patients were treated with escalating doses of L-BPA-F, eithermore » 350 mg/kg, 400 mg/kg, or 450 mg/kg, using 3 patients on each dose level. Adverse effects were assessed using National Cancer Institute Common Toxicity Criteria version 2.0. Results: Twenty-two patients entered the study. Twenty subjects had glioblastoma, and 2 patients had anaplastic astrocytoma, and the median cumulative dose of prior external beam radiotherapy was 59.4 Gy. The maximally tolerated L-BPA-F dose was reached at the 450 mg/kg level, where 4 of 6 patients treated had a grade 3 adverse event. Patients who were given >290 mg/kg of L-BPA-F received a higher estimated average planning target volume dose than those who received 290 mg/kg (median, 36 vs. 31 Gy [W, i.e., a weighted dose]; p = 0.018). The median survival time following BNCT was 7 months. Conclusions: BNCT administered with an L-BPA-F dose of up to 400 mg/kg as a 2-hour infusion is feasible in the treatment of malignant gliomas that recur after conventional radiation therapy.« less

Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 1: The predicted poor responder.

PubMed

van Tilborg, Theodora C; Torrance, Helen L; Oudshoorn, Simone C; Eijkemans, Marinus J C; Koks, Carolien A M; Verhoeve, Harold R; Nap, Annemiek W; Scheffer, Gabrielle J; Manger, A Petra; Schoot, Benedictus C; Sluijmer, Alexander V; Verhoeff, Arie; Groen, Henk; Laven, Joop S E; Mol, Ben Willem J; Broekmans, Frank J M

2017-12-01

Does an increased FSH dose result in higher cumulative live birth rates in women with a predicted poor ovarian response, apparent from a low antral follicle count (AFC), scheduled for IVF or ICSI? In women with a predicted poor ovarian response (AFC < 11) undergoing IVF/ICSI, an increased FSH dose (225/450 IU/day) does not improve cumulative live birth rates as compared to a standard dose (150 IU/day). In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can predict ovarian response to stimulation. The FSH starting dose is often adjusted based on the ORT from the belief that it will improve live birth rates. However, the existing RCTs on this topic, most of which show no benefit, are underpowered. Between May 2011 and May 2014, we performed an open-label multicentre RCT in women with an AFC < 11 (Dutch Trial Register NTR2657). The primary outcome was ongoing pregnancy achieved within 18 months after randomization and resulting in a live birth. We needed 300 women to assess whether an increased dose strategy would increase the cumulative live birth rate from 25 to 40% (two-sided alpha-error 0.05, power 80%). Women with an AFC ≤ 7 were randomized to an FSH dose of 450 IU/day or 150 IU/day, and women with an AFC 8-10 were randomized to 225 IU or 150 IU/day. In the standard group, dose adjustment was allowed in subsequent cycles based on pre-specified criteria. Both effectiveness and cost-effectiveness of the strategies were evaluated from an intention-to-treat perspective. In total, 511 women were randomized, 234 with an AFC ≤ 7 and 277 with an AFC 8-10. The cumulative live birth rate for increased versus standard dosing was 42.4% (106/250) versus 44.8% (117/261), respectively [relative risk (RR): 0.95 (95%CI, 0.78-1.15), P = 0.58]. As an increased dose strategy was more expensive [delta costs/woman: €1099 (95%CI, 562-1591)], standard FSH dosing was the dominant strategy in our economic analysis. Despite our training programme, the AFC might have suffered from inter-observer variation. As this open study permitted small dose adjustments between cycles, potential selective cancelling of cycles in women treated with 150 IU could have influenced the cumulative results. However, since first cycle live birth rates point in the same direction we consider it unlikely that the open design masked a potential benefit for the individualized strategy. Since an increased dose in women scheduled for IVF/ICSI with a predicted poor response (AFC < 11) does not improve live birth rates and is more expensive, we recommend using a standard dose of 150 IU/day in these women. This study was funded by The Netherlands Organisation for Health Research and Development (ZonMW number 171102020). T.C.T., H.L.T. and S.C.O. received an unrestricted personal grant from Merck BV. H.R.V. receives monetary compensation as a member on an external advisory board for Ferring pharmaceutical BV. B.W.J.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for OvsEva, Merck and Guerbet. F.J.M.B. receives monetary compensation as a member of the external advisory board for Ferring pharmaceutics BV (the Netherlands) and Merck Serono (the Netherlands) for consultancy work for Gedeon Richter (Belgium) and Roche Diagnostics on automated AMH assay development (Switzerland) and for a research cooperation with Ansh Labs (USA). All other authors have nothing to declare. Registered at the ICMJE-recognized Dutch Trial Registry (www.trialregister.nl). Registration number NTR2657. 20 December 2010. 12 May 2011. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

A comprehensive dose reconstruction methodology for former rocketdyne/atomics international radiation workers.

PubMed

Boice, John D; Leggett, Richard W; Ellis, Elizabeth Dupree; Wallace, Phillip W; Mumma, Michael; Cohen, Sarah S; Brill, A Bertrand; Chadda, Bandana; Boecker, Bruce B; Yoder, R Craig; Eckerman, Keith F

2006-05-01

Incomplete radiation exposure histories, inadequate treatment of internally deposited radionuclides, and failure to account for neutron exposures can be important uncertainties in epidemiologic studies of radiation workers. Organ-specific doses from lifetime occupational exposures and radionuclide intakes were estimated for an epidemiologic study of 5,801 Rocketdyne/Atomics International (AI) radiation workers engaged in nuclear technologies between 1948 and 1999. The entire workforce of 46,970 Rocketdyne/AI employees was identified from 35,042 Kardex work histories cards, 26,136 electronic personnel listings, and 14,189 radiation folders containing individual exposure histories. To obtain prior and subsequent occupational exposure information, the roster of all workers was matched against nationwide dosimetry files from the Department of Energy, the Nuclear Regulatory Commission, the Landauer dosimetry company, the U.S. Army, and the U.S. Air Force. Dosimetry files of other worker studies were also accessed. Computation of organ doses from radionuclide intakes was complicated by the diversity of bioassay data collected over a 40-y period (urine and fecal samples, lung counts, whole-body counts, nasal smears, and wound and incident reports) and the variety of radionuclides with documented intake including isotopes of uranium, plutonium, americium, calcium, cesium, cerium, zirconium, thorium, polonium, promethium, iodine, zinc, strontium, and hydrogen (tritium). Over 30,000 individual bioassay measurements, recorded on 11 different bioassay forms, were abstracted. The bioassay data were evaluated using ICRP biokinetic models recommended in current or upcoming ICRP documents (modified for one inhaled material to reflect site-specific information) to estimate annual doses for 16 organs or tissues taking into account time of exposure, type of radionuclide, and excretion patterns. Detailed internal exposure scenarios were developed and annual internal doses were derived on a case-by-case basis for workers with committed equivalent doses indicated by screening criteria to be greater than 10 mSv to the organ with the highest internal dose. Overall, 5,801 workers were monitored for radiation at Rocketdyne/AI: 5,743 for external exposure and 2,232 for internal intakes of radionuclides; 41,169 workers were not monitored for radiation. The mean cumulative external dose based on Rocketdyne/AI records alone was 10.0 mSv, and the dose distribution was highly skewed with most workers experiencing low cumulative doses and only a few with high doses (maximum 500 mSv). Only 45 workers received greater than 200 mSv while employed at Rocketdyne/AI. However, nearly 32% (or 1,833) of the Rocketdyne/AI workers had been monitored for radiation at other nuclear facilities and incorporation of these doses increased the mean dose to 13.5 mSv (maximum 1,005 mSv) and the number of workers with >200 mSv to 69. For a small number of workers (n=292), lung doses from internal radionuclide intakes were relatively high (mean 106 mSv; maximum 3,560 mSv) and increased the overall population mean dose to 19.0 mSv and the number of workers with lung dose>200 mSv to 109. Nearly 10% of the radiation workers (584) were monitored for neutron exposures (mean 1.2 mSv) at Rocketdyne/AI, and another 2% were monitored for neutron exposures elsewhere. Interestingly, 1,477 workers not monitored for radiation at Rocketdyne/AI (3.6%) were found to have worn dosimeters at other nuclear facilities (mean external dose of 2.6 mSv, maximum 188 mSv). Without considering all sources of occupational exposure, an incorrect characterization of worker exposure would have occurred with the potential to bias epidemiologic results. For these pioneering workers in the nuclear industry, 26.5% of their total occupational dose (collective dose) was received at other facilities both prior to and after employment at Rocketdyne/AI. In addition, a small number of workers monitored for internal radionuclides contributed disproportionately to the number of workers with high lung doses. Although nearly 12% of radiation workers had been monitored for neutron exposures during their career, the cumulative dose levels were small in comparison with other external and internal exposure. Risk estimates based on nuclear worker data must be interpreted cautiously if internally deposited radionuclides and occupational doses received elsewhere are not considered.

Radiation dose escalation or longer androgen suppression for locally advanced prostate cancer? Data from the TROG 03.04 RADAR trial.

PubMed

Denham, James W; Steigler, Allison; Joseph, David; Lamb, David S; Spry, Nigel A; Duchesne, Gillian; Atkinson, Chris; Matthews, John; Turner, Sandra; Kenny, Lizbeth; Tai, Keen-Hun; Gogna, Nirdosh Kumar; Gill, Suki; Tan, Hendrick; Kearvell, Rachel; Murray, Judy; Ebert, Martin; Haworth, Annette; Kennedy, Angel; Delahunt, Brett; Oldmeadow, Christopher; Holliday, Elizabeth G; Attia, John

2015-06-01

The relative effects of radiation dose escalation (RDE) and androgen suppression (AS) duration on local prostatic progression (LP) remain unclear. We addressed this in the TROG 03.04 RADAR trial by incorporating a RDE programme by stratification at randomisation. Men were allocated 6 or 18 months AS±18 months zoledronate (Z). The main endpoint was a composite of clinically diagnosed LP or PSA progression with a PSA doubling time ⩾6 months. Fine and Gray competing risk modelling with adjustment for site clustering produced cumulative incidence estimates at 6.5 years for each RDE group. Composite LP declined coherently in the 66, 70 and 74 Gy external beam dosing groups and was lowest in the high dose rate brachytherapy boost (HDRB) group. At 6.5 years, adjusted cumulative incidences were 22%, 15%, 13% and 7% respectively. Compared to 6 months AS, 18 months AS also significantly reduced LP (p<0.001). Post-radiation urethral strictures were documented in 45 subjects and increased incrementally in the dosing groups. Crude incidences were 0.8%, 0.9%, 3.8% and 12.7% respectively. RDE and increasing AS independently reduce LP and increase urethral strictures. The risks and benefits to the individual must be balanced when selecting radiation dose and AS duration. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Age- and gender-specific estimates of cumulative CT dose over 5 years using real radiation dose tracking data in children.

PubMed

Lee, Eunsol; Goo, Hyun Woo; Lee, Jae-Yeong

2015-08-01

It is necessary to develop a mechanism to estimate and analyze cumulative radiation risks from multiple CT exams in various clinical scenarios in children. To identify major contributors to high cumulative CT dose estimates using actual dose-length product values collected for 5 years in children. Between August 2006 and July 2011 we reviewed 26,937 CT exams in 13,803 children. Among them, we included 931 children (median age 3.5 years, age range 0 days-15 years; M:F = 533:398) who had 5,339 CT exams. Each child underwent at least three CT scans and had accessible radiation dose reports. Dose-length product values were automatically extracted from DICOM files and we used recently updated conversion factors for age, gender, anatomical region and tube voltage to estimate CT radiation dose. We tracked the calculated CT dose estimates to obtain a 5-year cumulative value for each child. The study population was divided into three groups according to the cumulative CT dose estimates: high, ≥30 mSv; moderate, 10-30 mSv; and low, <10 mSv. We reviewed clinical data and CT protocols to identify major contributors to high and moderate cumulative CT dose estimates. Median cumulative CT dose estimate was 5.4 mSv (range 0.5-71.1 mSv), and median number of CT scans was 4 (range 3-36). High cumulative CT dose estimates were most common in children with malignant tumors (57.9%, 11/19). High frequency of CT scans was attributed to high cumulative CT dose estimates in children with ventriculoperitoneal shunt (35 in 1 child) and malignant tumors (range 18-49). Moreover, high-dose CT protocols, such as multiphase abdomen CT (median 4.7 mSv) contributed to high cumulative CT dose estimates even in children with a low number of CT scans. Disease group, number of CT scans, and high-dose CT protocols are major contributors to higher cumulative CT dose estimates in children.

Cumulative effective dose associated with radiography and CT of adolescents with spinal injuries.

PubMed

Lemburg, Stefan P; Peters, Soeren A; Roggenland, Daniela; Nicolas, Volkmar; Heyer, Christoph M

2010-12-01

The purpose of this study was to analyze the quantity and distribution of cumulative effective doses in diagnostic imaging of adolescents with spinal injuries. At a level 1 trauma center from July 2003 through June 2009, imaging procedures during initial evaluation and hospitalization and after discharge of all patients 10-20 years old with spinal fractures were retrospectively analyzed. The cumulative effective doses for all imaging studies were calculated, and the doses to patients with spinal injuries who had multiple traumatic injuries were compared with the doses to patients with spinal injuries but without multiple injuries. The significance level was set at 5%. Imaging studies of 72 patients (32 with multiple injuries; average age, 17.5 years) entailed a median cumulative effective dose of 18.89 mSv. Patients with multiple injuries had a significantly higher total cumulative effective dose (29.70 versus 10.86 mSv, p < 0.001) mainly owing to the significantly higher CT-related cumulative effective dose to multiple injury patients during the initial evaluation (18.39 versus 2.83 mSv, p < 0.001). Overall, CT accounted for 86% of the total cumulative effective dose. Adolescents with spinal injuries receive a cumulative effective dose equal to that of adult trauma patients and nearly three times that of pediatric trauma patients. Areas of focus in lowering cumulative effective dose should be appropriate initial estimation of trauma severity and careful selection of CT scan parameters.

Cancer mortality and morbidity among plutonium workers at the Sellafield plant of British Nuclear Fuels

PubMed Central

Omar, R Z; Barber, J A; Smith, P G

1999-01-01

The mortality of all 14 319 workers employed at the Sellafield plant of British Nuclear Fuels between 1947 and 1975 was studied up to the end of 1992, and cancer incidence was examined from 1971 to 1986, in relation to their exposures to plutonium and to external radiation. The cancer mortality rate was 5% lower than that of England and Wales and 3% less than that of Cumbria. The significant excesses of deaths from cancer of the pleura and thyroid found in an earlier study persist with further follow-up (14 observed, 4.0 expected for pleura; 6 observed, 2.2 expected for thyroid). All of the deaths from pleural cancer were among radiation workers. For neither site was there a significant association between the risk of the cancer and accumulated radiation dose. There were significant deficits of deaths from cancers of mouth and pharynx, liver and gall bladder, and larynx and leukaemia when compared with the national rates. Among all radiation workers, there was a significant positive association between accumulated external radiation dose and mortality from cancers of ill-defined and secondary sites (10-year lag, P = 0.04), leukaemia (no lag, P = 0.03; 2-year lag, P = 0.05), multiple myeloma (20-year lag, P = 0.02), all lymphatic and haematopoietic cancers (20-year lag, P = 0.03) and all causes of death combined (20-year lag, P = 0.008). Among plutonium workers, there were significant excesses of deaths from cancer of the breast (6 observed, 2.6 expected) and ill-defined and secondary cancers (29 observed, 20.1 expected). No significant positive trends were observed between the risk of deaths from cancers of any specific site, or all cancers combined, and cumulative plutonium and external radiation doses. For no cancer site was there a significant excess of cancer registrations compared with rates for England and Wales. Analysis of trends in cancer incidence showed significant increases in risk with cumulative plutonium plus external radiation doses for all lymphatic and haematopoietic neoplasms for 0-, 10- and 20-year lag periods. Taken as a whole, our findings do not suggest that workers at Sellafield who have been exposed to plutonium are at an overall significantly increased risk of cancer compared with other radiation workers. © 1999 Cancer Research Campaign PMID:10098774

Cancer mortality and morbidity among plutonium workers at the Sellafield plant of British Nuclear Fuels.

PubMed

Omar, R Z; Barber, J A; Smith, P G

1999-03-01

The mortality of all 14 319 workers employed at the Sellafield plant of British Nuclear Fuels between 1947 and 1975 was studied up to the end of 1992, and cancer incidence was examined from 1971 to 1986, in relation to their exposures to plutonium and to external radiation. The cancer mortality rate was 5% lower than that of England and Wales and 3% less than that of Cumbria. The significant excesses of deaths from cancer of the pleura and thyroid found in an earlier study persist with further follow-up (14 observed, 4.0 expected for pleura; 6 observed, 2.2 expected for thyroid). All of the deaths from pleural cancer were among radiation workers. For neither site was there a significant association between the risk of the cancer and accumulated radiation dose. There were significant deficits of deaths from cancers of mouth and pharynx, liver and gall bladder, and larynx and leukaemia when compared with the national rates. Among all radiation workers, there was a significant positive association between accumulated external radiation dose and mortality from cancers of ill-defined and secondary sites (10-year lag, P = 0.04), leukaemia (no lag, P = 0.03; 2-year lag, P = 0.05), multiple myeloma (20-year lag, P = 0.02), all lymphatic and haematopoietic cancers (20-year lag, P= 0.03) and all causes of death combined (20-year lag, P= 0.008). Among plutonium workers, there were significant excesses of deaths from cancer of the breast (6 observed, 2.6 expected) and ill-defined and secondary cancers (29 observed, 20.1 expected). No significant positive trends were observed between the risk of deaths from cancers of any specific site, or all cancers combined, and cumulative plutonium and external radiation doses. For no cancer site was there a significant excess of cancer registrations compared with rates for England and Wales. Analysis of trends in cancer incidence showed significant increases in risk with cumulative plutonium plus external radiation doses for all lymphatic and haematopoietic neoplasms for 0-, 10- and 20-year lag periods. Taken as a whole, our findings do not suggest that workers at Sellafield who have been exposed to plutonium are at an overall significantly increased risk of cancer compared with other radiation workers.

Cumulative iron dose and resistance to erythropoietin.

PubMed

Rosati, A; Tetta, C; Merello, J I; Palomares, I; Perez-Garcia, R; Maduell, F; Canaud, B; Aljama Garcia, P

2015-10-01

Optimizing anemia treatment in hemodialysis (HD) patients remains a priority worldwide as it has significant health and financial implications. Our aim was to evaluate in a large cohort of chronic HD patients in Fresenius Medical Care centers in Spain the value of cumulative iron (Fe) dose monitoring for the management of iron therapy in erythropoiesis-stimulating agent (ESA)-treated patients, and the relationship between cumulative iron dose and risk of hospitalization. Demographic, clinical and laboratory parameters from EuCliD(®) (European Clinical Dialysis Database) on 3,591 patients were recorded including ESA dose (UI/kg/week), erythropoietin resistance index (ERI) [U.I weekly/kg/gr hemoglobin (Hb)] and hospitalizations. Moreover the cumulative Fe dose (mg/kg of bodyweight) administered over the last 2 years was calculated. Univariate and multivariate analyses were performed to identify the main predictors of ESA resistance and risk of hospitalization. Patients belonging to the 4th quartile of ERI were defined as hypo-responders. The 2-year iron cumulative dose was significantly higher in the 4th quartile of ERI. In hypo-responders, 2-year cumulative iron dose was the only iron marker associated with ESA resistance. At case-mix adjusted multivariate analysis, 2-year iron cumulative dose was an independent predictor of hospitalization risk. In ESA-treated patients cumulative Fe dose could be a useful tool to monitor the appropriateness of Fe therapy and to prevent iron overload. To establish whether the associations between cumulative iron dose, ERI and hospitalization risk are causal or attributable to selection bias by indication, clinical trials are necessary.

Assessing cost and effectiveness of radiation decontamination in Fukushima Prefecture, Japan.

PubMed

Yasutaka, Tetsuo; Naito, Wataru

2016-01-01

Despite the enormous cost of radiation decontamination in Fukushima Prefecture, it is not clear what levels of reduction in external radiation exposure are possible in the Special Decontamination Area, the Intensive Contamination Survey Areas and the whole of Fukushima. The objective of this study was to evaluate the cost and effectiveness of radiation decontamination in Fukushima Prefecture in its entirety. Using a geographic information system, we calculated the costs of removal, storage containers, transport, and temporary and interim storage facilities as well as the reduction in air dose rate for a cumulative external exposure for 9000 1 km × 1 km mesh units incorporating 51 municipalities. The decontamination cost for the basic scenario, for which forested areas within 20 m of habitation areas were decontaminated, was JPY2.53-5.12 trillion; the resulting reduction in annual external dose was about 2500 person-Sv. The transport, storage, and administrative costs of decontamination waste and removed soil reached JPY1.55-2.12 trillion under this scenario. Although implementing decontamination of all forested areas provides some major reductions in the external radiation dose for the average inhabitant, decontamination costs could potentially exceed JPY16 trillion. These results indicate that technologies for reducing the volume of decontamination waste and removed soil should be considered to reduce storage costs and that further discussions about forest decontamination policies are needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rectal Bleeding After High-Dose-Rate Brachytherapy Combined With Hypofractionated External-Beam Radiotherapy for Localized Prostate Cancer: The Relationship Between Dose-Volume Histogram Parameters and the Occurrence Rate

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

Okamoto, Masahiko, E-mail: masaoka@showa.gunma-u.ac.jp; Ishikawa, Hitoshi; Ebara, Takeshi

2012-02-01

Purpose: To determine the predictive risk factors for Grade 2 or worse rectal bleeding after high-dose-rate brachytherapy (HDR-BT) combined with hypofractionated external-beam radiotherapy (EBRT) for prostate cancer using dose-volume histogram analysis. Methods and Materials: The records of 216 patients treated with HDR-BT combined with EBRT were analyzed. The treatment protocols for HDR-BT were 5 Gy Multiplication-Sign five times in 3 days or 7 Gy Multiplication-Sign three, 10.5 Gy Multiplication-Sign two, or 9 Gy Multiplication-Sign two in 2 days. The EBRT doses ranged from 45 to 51 Gy with a fractional dose of 3 Gy. Results: In 20 patients Grade 2more » or worse rectal bleeding developed, and the cumulative incidence rate was 9% at 5 years. By converting the HDR-BT and EBRT radiation doses into biologic effective doses (BED), the BED{sub 3} at rectal volumes of 5% and 10% in the patients who experienced bleeding were significantly higher than those in the remaining 196 patients. Univariate analysis showed that a higher rectal BED{sub 3-5%} and the use of fewer needles in brachytherapy were correlated with the incidence of bleeding, but BED{sub 3-5%} was found to be the only significant factor on multivariate analysis. Conclusions: The radiation dose delivered to small rectal lesions as 5% is important for predicting Grade 2 or worse rectal bleeding after HDR-BT combined with EBRT for prostate cancer.« less

Radiotherapy and risk of implantable cardioverter-defibrillator malfunctions: experimental data from direct exposure at increasing doses.

PubMed

Zecchin, Massimo; Artico, Jessica; Morea, Gaetano; Severgnini, Mara; Bianco, Elisabetta; De Luca, Antonio; Fantasia, Anna Zorzin; Salvatore, Luca; Milan, Vittorino; Lucarelli, Matteo; Dissegna, Roberta; Cannatà, Antonio; Sinagra, Gianfranco

2018-04-01

During radiotherapy, in patients with implantable cardioverter-defibrillators (ICDs) malfunctions are considered more likely if doses more than 2 Gy reach the ICD site; however, most malfunctions occur with high-energy (>10 MV) radiations, and the risk is less defined using 6-MV linear accelerators. The purpose of the study is to experimentally evaluate the occurrence of malfunctions in ICDs radiated with a 6-MV linear accelerator at increasing photon doses. Thirty-two ICDs from all manufacturers (31 explanted and one demo) were evaluated; all devices with a sufficient battery charge underwent multiple radiations with a 6-MV photon beam reaching a cumulative dose at ICD site of 0.5, 1, 2, 3, 5 and 10 Gy and interrogated after every session. All antitachycardia therapies were left enabled; two ICDs were connected to a rhythm simulator (one simulating a complete atrioventricular block without ventricular activity) and visually monitored by external ECG and the ICD programmer during radiation. Thirteen ICDs were excluded before radiation because of battery depletion; after radiation up to the cumulative dose at the cardiac implantable electronic device site of 10 Gy, in the remaining 19 devices, programmation and battery charge remained unchanged and no switch to safety mode was observed; oversensing, pacing inhibition or inappropriate antitachycardia therapy were neither recorded nor visually observed during radiation. With a low-energy accelerator, neither malfunctions nor electromagnetic interferences were detected radiating the ICDs at doses usually reaching the ICD pocket during radiotherapy sessions. In this context, magnet application to avoid oversensing and inappropriate therapy seems, therefore, useless.

A case control study of multiple myeloma at four nuclear facilities.

PubMed

Wing, S; Richardson, D; Wolf, S; Mihlan, G; Crawford-Brown, D; Wood, J

2000-04-01

Reported elevations of multiple myeloma among nuclear workers exposed to external penetrating ionizing radiation, based on small numbers of cases, prompted this multi-facility study of workers at US Department of Energy facilities. Ninety-eight multiple myeloma deaths and 391 age-matched controls were selected from the combined roster of 115,143 workers hired before 1979 at Hanford, Los Alamos National Laboratory, Oak Ridge National Laboratory, and the Savannah River site. These workers were followed for vital status through 1990 (1986 for Hanford). Demographic, work history, and occupational exposure data were derived from personnel, occupational medicine, industrial hygiene, and health physics records. Exposure-disease associations were evaluated using conditional logistic regression. Cases were disproportionately African American, male, and hired prior to 1948. Lifetime cumulative whole body ionizing radiation dose was not associated with multiple myeloma, however, there was a significant effect of age at exposure, with positive associations between multiple myeloma and doses received at older ages. Dose response associations increased in magnitude with exposure age (from 40 to 50) and lag assumption (from 5 to 15 years), while a likelihood ratio goodness of fit test reached the highest value for cumulative doses received at ages above 45 with a 5-year lag (X2=5.43,1 df; relative risk = 6.9% per 10 mSv). Dose response associations persisted with adjustment for potential confounders. Multiple myeloma was associated with low level whole body penetrating ionizing radiation doses at older ages. The exposure age effect is at odds with interpretations of A-bomb survivor studies but in agreement with several studies of cancer among nuclear workers.

A study on comparison of Gafchromic EBT2 film response under single and cumulative exposure conditions

PubMed Central

Ganapathy, K.; Kurup, P.G.G.; Murali, V.; Muthukumaran, M.; Velmurugan, J.

2013-01-01

Gafchromic films are used as dosimeter for in vivo and in phantom dose measurements. The dose response of Gafchromic EBT2 film under single and repeated exposure conditions is compared in this study to analyze the usability of Gafchromic EBT2 films in cumulative dose measurements. The post-irradiation change in response of the film is studied for up to 4 days after irradiation. The effect of repeated exposure to scanner light on the response of the film is also studied. To check usability of Gafchromic EBT2 films in cumulative dose measurements, three EBT2 films were exposed to a daily fraction dose of 100 cGy, 150 cGy and 200 cGy, respectively, for 4 days. The dose response of the films exposed to cumulative irradiation was compared with the dose measured from films exposed to the same dose but in a single exposure. It is observed that the post-irradiation darkening of the film does not saturate and continue to take place even 4 days after irradiation. The dose measured from the EBT2 films after 4 days from irradiation was around 2% higher than the dose measured from the same films at 24 hours post-irradiation. It was also observed that the repeated exposure to scanner light does not produce any significant change in the film response. The dose response of films exposed to cumulative irradiation agrees with the dose response of films exposed to the same dose in a single irradiation with less than 3% difference. Gafchromic EBT2 films can be used to measure the cumulative dose delivered over multiple fractions, when the delivered dose is uniform across the film. PMID:24672151

Stable and unstable chromosomal aberrations among Finnish nuclear power plant workers.

PubMed

Lindholm, C

2001-01-01

Twenty nuclear power plant workers with relatively high recorded cumulative doses were studied using FISH chromosome painting and dicentric analysis after solid Giemsa staining. The results indicated that chronic exposure to ionising radiation can be detected on the group level using translocation analysis after chromosome painting, although the mean cumulative dose was approximately 100 mSv. A significant association between translocation frequency and cumulative dose was observed. Variability in the translocation yields among workers with similar recorded doses was large, resulting in a poor correlation between translocation frequencies and documented doses on the individual level. The yields of dicentric and acentric chromosomes were not correlated with the cumulative dose, indicating the inability of unstable aberrations to monitor long-term exposures. It was also shown that the unstable aberrations were not correlated with the most recent annual dose.

Radiation exposure assessment for portsmouth naval shipyard health studies.

PubMed

Daniels, R D; Taulbee, T D; Chen, P

2004-01-01

Occupational radiation exposures of 13,475 civilian nuclear shipyard workers were investigated as part of a retrospective mortality study. Estimates of annual, cumulative and collective doses were tabulated for future dose-response analysis. Record sets were assembled and amended through range checks, examination of distributions and inspection. Methods were developed to adjust for administrative overestimates and dose from previous employment. Uncertainties from doses below the recording threshold were estimated. Low-dose protracted radiation exposures from submarine overhaul and repair predominated. Cumulative doses are best approximated by a hybrid log-normal distribution with arithmetic mean and median values of 20.59 and 3.24 mSv, respectively. The distribution is highly skewed with more than half the workers having cumulative doses <10 mSv and >95% having doses <100 mSv. The maximum cumulative dose is estimated at 649.39 mSv from 15 person-years of exposure. The collective dose was 277.42 person-Sv with 96.8% attributed to employment at Portsmouth Naval Shipyard.

Cumulative cisplatin dose in concurrent chemoradiotherapy for head and neck cancer: A systematic review.

PubMed

Strojan, Primož; Vermorken, Jan B; Beitler, Jonathan J; Saba, Nabil F; Haigentz, Missak; Bossi, Paolo; Worden, Francis P; Langendijk, Johannes A; Eisbruch, Avraham; Mendenhall, William M; Lee, Anne W M; Harrison, Louis B; Bradford, Carol R; Smee, Robert; Silver, Carl E; Rinaldo, Alessandra; Ferlito, Alfio

2016-04-01

The optimal cumulative dose and timing of cisplatin administration in various concurrent chemoradiotherapy protocols for nonmetastatic head and neck squamous cell carcinoma (HNSCC) has not been determined. The absolute survival benefit at 5 years of concurrent chemoradiotherapy protocols versus radiotherapy alone observed in prospective randomized trials reporting on the use of cisplatin monochemotherapy for nonnasopharyngeal HNSCC was extracted. In the case of nonrandomized studies, the outcome results at 2 years were compared between groups of patients receiving different cumulative cisplatin doses. Eleven randomized trials and 7 nonrandomized studies were identified. In 6 definitive radiotherapy phase III trials, a statistically significant association (p = .027) between cumulative cisplatin dose, independent of the schedule, and overall survival benefit was observed for higher doses. Results support the conclusion that the cumulative dose of cisplatin in concurrent chemoradiation protocols for HNSCC has a significant positive correlation with survival. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2151-E2158, 2016. © 2015 Wiley Periodicals, Inc.

The Role of Family Income Dynamics in Predicting Trajectories of Internalizing and Externalizing Problems.

PubMed

Miller, Portia; Votruba-Drzal, Elizabeth

2017-04-01

Economic disparities in children's behavioral functioning have been observed in prior research. Yet, studies have ignored important perspectives from developmental psychopathology and have not delineated how aspects of income dynamics (i.e., cumulative family income versus income volatility) differentially relate to behavior problems. To address these limitations, the current study examined how both cumulative income and income volatility predict trajectories of children's internalizing and externalizing problems from kindergarten through fifth grade in a nationally representative sample of 10,900 children (51.4 % male). Results showed four distinct trajectories of internalizing problems and five distinct externalizing trajectories. Family income dynamics were related to trajectory group membership. Specifically, increased cumulative income decreased risk of membership in mid-increasing and mid-stable internalizing groups, and children whose families experienced multiple waves of income loss were 2.4 times as likely to be in the mid-increasing group instead of the low-stable group. With respect to externalizing, higher cumulative income increased the likelihood of belonging in the group exhibiting stably low externalizing problems. Experiencing income loss increased the risk of belonging in the trajectory group exhibiting chronically high externalizing behaviors. These results enhance our knowledge of the role of family income in the development of behavior problems.

Cumulative radiation exposure and associated cancer risk estimates for scoliosis patients: Impact of repetitive full spine radiography.

PubMed

Law, Martin; Ma, Wang-Kei; Lau, Damian; Chan, Eva; Yip, Lawrance; Lam, Wendy

2016-03-01

To quantitatively evaluate the cumulative effective dose and associated cancer risk for scoliotic patients undergoing repetitive full spine radiography during their diagnosis and follow up periods. Organ absorbed doses of full spine exposed scoliotic patients at different age were computer simulated with the use of PCXMC software. Gender specific effective dose was then calculated with the ICRP-103 approach. Values of lifetime attributable cancer risk for patients exposed at different age were calculated for both patient genders and for Asian and Western population. Mathematical fitting for effective dose and for lifetime attributable cancer risk, as function of exposed age, was analytically obtained to quantitatively estimate patient cumulated effective dose and cancer risk. The cumulative effective dose of full spine radiography with posteroanterior and lateral projection for patients exposed annually at age between 5 and 30 years using digital radiography system was calculated as 15mSv. The corresponding cumulative lifetime attributable cancer risk for Asian and Western population was calculated as 0.08-0.17%. Female scoliotic patients would be at a statistically significant higher cumulated cancer risk than male patients under the same full spine radiography protocol. We demonstrate the use of computer simulation and analytic formula to quantitatively obtain the cumulated effective dose and cancer risk at any age of exposure, both of which are valuable information to medical personnel and patients' parents concern about radiation safety in repetitive full spine radiography. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Randomised controlled trials define shape of dose-response for Pollinex Quattro Birch allergoid immunotherapy.

PubMed

Worm, Margitta; Higenbottam, Tim; Pfaar, Oliver; Mösges, Ralph; Aberer, Werner; Gunawardena, Kulasiri; Wessiepe, Dorothea; Lee, Denise; Kramer, Matthias F; Skinner, Murray; Lees, Bev; Zielen, Stefan

2018-05-19

The Birch Allergoid, Tyrosine Adsorbate, Monophosphoryl Lipid A (POLLINEX ® Quattro Plus 1.0 ml Birch 100%) is an effective, well-tolerated short course subcutaneous immunotherapy. We performed two phase II studies to determine its optimal cumulative dose. The studies were conducted in Germany, Austria and Poland (EudraCT numbers: 2012-004336-28 PQBirch203 and 2015-000984-15 PQBirch204) using a wide range of cumulative doses. In both studies, subjects were administered 6 therapy injections weekly outside the pollen season. Conjunctival Provocation Tests were performed at screening, baseline and 3-4 weeks after completing treatment, to quantify the reduction of Total Symptom Scores (as the primary endpoint) with each cumulative dose. Multiple Comparison Procedure and Modelling analysis was used to test for the dose-response, shape of the curve, and estimation of the median effective dose (ED 50 ), a measure of potency. Statistically significant dose-responses (p<0.01 & 0.001) were seen respectively. The highest cumulative dose in PQBirch204 (27300 standardised units [SU]) approached a plateau. Potency of the PQ Birch was demonstrated by an ED 50 2723 SU, just over half the current dose. Prevalence of treatment-emergent adverse events was similar for active doses, most being short-lived and mild. Compliance was over 85% in all groups. Increasing the cumulative dose of PQ Birch 5.5-fold from 5100 to 27300 SU achieved an absolute point difference from placebo of 1.91, a relative difference 32.3% and an increase of efficacy of 50%, without compromising safety. The cumulative dose-response was confirmed to be curvilinear in shape. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Dose-response relationships between internally-deposited uranium and select health outcomes in gaseous diffusion plant workers, 1948-2011.

PubMed

Yiin, James H; Anderson, Jeri L; Bertke, Stephen J; Tollerud, David J

2018-05-09

To examine dose-response relationships between internal uranium exposures and select outcomes among a cohort of uranium enrichment workers. Cox regression was conducted to examine associations between selected health outcomes and cumulative internal uranium with consideration for external ionizing radiation, work-related medical X-rays and contaminant radionuclides technetium ( 99 Tc) and plutonium ( 239 Pu) as potential confounders. Elevated and monotonically increasing mortality risks were observed for kidney cancer, chronic renal diseases, and multiple myeloma, and the association with internal uranium absorbed organ dose was statistically significant for multiple myeloma. Adjustment for potential confounders had minimal impact on the risk estimates. Kidney cancer, chronic renal disease, and multiple myeloma mortality risks were elevated with increasing internal uranium absorbed organ dose. The findings add to evidence of an association between internal exposure to uranium and cancer. Future investigation includes a study of cancer incidence in this cohort. © 2018 Wiley Periodicals, Inc.

DOSE-RESPONSE BEHAVIOR OF ANDROGENIC AND ANTIANDROGENIC CHEMICALS: IMPLICATIONS FOR LOW-DOSE EXTRAPOLATION AND CUMULATIVE TOXICITY

EPA Science Inventory

DOSE-RESPONSE BEHAVIOR OF ANDROGENIC AND ANTIANDROGENIC CHEMICALS: IMPLICATIONS FOR LOW-DOSE EXTRAPOLATION AND CUMULATIVE TOXICITY. LE Gray Jr, C Wolf, J Furr, M Price, C Lambright, VS Wilson and J Ostby. USEPA, ORD, NHEERL, EB, RTD, RTP, NC, USA.
Dose-response behavior of a...

Application of the ELDO approach to assess cumulative eye lens doses for interventional cardiologists.

PubMed

Farah, J; Struelens, L; Auvinen, A; Jacob, S; Koukorava, C; Schnelzer, M; Vanhavere, F; Clairand, I

2015-04-01

In preparation of a large European epidemiological study on the relation between eye lens dose and the occurrence of lens opacities, the European ELDO project focused on the development of practical methods to estimate retrospectively cumulative eye lens dose for interventional medical professionals exposed to radiation. The present paper applies one of the ELDO approaches, correlating eye lens dose to whole-body doses, to assess cumulative eye lens dose for 14 different Finnish interventional cardiologists for whom annual whole-body dose records were available for their entire working period. The estimated cumulative left and right eye lens dose ranged from 8 to 264 mSv and 6 to 225 mSv, respectively. In addition, calculations showed annual eye lens doses sometimes exceeding the new ICRP annual limit of 20 mSv. The work also highlights the large uncertainties associated with the application of such an approach proving the need for dedicated dosimetry systems in the routine monitoring of the eye lens dose. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Longitudinal Pathways from Cumulative Contextual Risk at Birth to School Functioning in Adolescence: Analysis of Mediation Effects and Gender Moderation.

PubMed

January, Stacy-Ann A; Mason, W Alex; Savolainen, Jukka; Solomon, Starr; Chmelka, Mary B; Miettunen, Jouko; Veijola, Juha; Moilanen, Irma; Taanila, Anja; Järvelin, Marjo-Riitta

2017-01-01

Children and adolescents exposed to multiple contextual risks are more likely to have academic difficulties and externalizing behavior problems than those who experience fewer risks. This study used data from the Northern Finland Birth Cohort 1986 (a population-based study; N = 6961; 51 % female) to investigate (a) the impact of cumulative contextual risk at birth on adolescents' academic performance and misbehavior in school, (b) learning difficulties and/or externalizing behavior problems in childhood as intervening mechanisms in the association of cumulative contextual risk with functioning in adolescence, and (c) potential gender differences in the predictive associations of cumulative contextual risk at birth with functioning in childhood or adolescence. The results of the structural equation modeling analysis suggested that exposure to cumulative contextual risk at birth had negative associations with functioning 16 years later, and academic difficulties and externalizing behavior problems in childhood mediated some of the predictive relations. Gender, however, did not moderate any of the associations. Therefore, the findings of this study have implications for the prevention of learning and conduct problems in youth and future research on the impact of cumulative risk exposure.

Longitudinal Pathways from Cumulative Contextual Risk at Birth to School Functioning in Adolescence: Analysis of Mediation Effects and Gender Moderation

PubMed Central

January, Stacy-Ann A.; Mason, W. Alex; Savolainen, Jukka; Solomon, Starr; Chmelka, Mary B.; Miettunen, Jouko; Veijola, Juha; Moilanen, Irma; Taanila, Anja; Järvelin, Marjo-Riitta

2016-01-01

Children and adolescents exposed to multiple contextual risks are more likely to have academic difficulties and externalizing behavior problems than those who experience fewer risks. This study used data from the Northern Finland Birth Cohort 1986 (a population-based study; N = 6,961; 51% female) to investigate (a) the impact of cumulative contextual risk at birth on adolescents’ academic performance and misbehavior in school, (b) learning difficulties and/or externalizing behavior problems in childhood as intervening mechanisms in the association of cumulative contextual risk with functioning in adolescence, and (c) potential gender differences in the predictive associations of cumulative contextual risk at birth with functioning in childhood or adolescence. The results of the structural equation modeling analysis suggested that exposure to cumulative contextual risk at birth had negative associations with functioning 16 years later, and academic difficulties and externalizing behavior problems in childhood mediated some of the predictive relations. Gender, however, did not moderate any of the associations. Therefore, the findings of this study have implications for the prevention of learning and conduct problems in youth and future research on the impact of cumulative risk exposure. PMID:27665276

Switching From Age-Based Stimulus Dosing to Dose Titration Protocols in Electroconvulsive Therapy: Empirical Evidence for Better Patient Outcomes With Lower Peak and Cumulative Energy Doses.

PubMed

O'Neill-Kerr, Alex; Yassin, Anhar; Rogers, Stephen; Cornish, Janie

2017-09-01

The aim of this study was to test the proposition that adoption of a dose titration protocol may be associated with better patient outcomes, at lower treatment dose, and with comparable cumulative dose to that in patients treated using an age-based stimulus dosing protocol. This was an analysis of data assembled from archived records and based on cohorts of patients treated respectively on an age-based stimulus dosing protocol and on a dose titration protocol in the National Health Service in England. We demonstrated a significantly better response in the patient cohort treated with dose titration than with age-based stimulus dosing. Peak doses were less and the total cumulative dose was less in the dose titration group than in the age-based stimulus dosing group. Our findings are consistent with superior outcomes in patients treated using a dose titration protocol when compared with age-based stimulus dosing in a similar cohort of patients.

Co-registration of cone beam CT and planning CT in head and neck IMRT dose estimation: a feasible adaptive radiotherapy strategy

PubMed Central

Yip, C; Thomas, C; Michaelidou, A; James, D; Lynn, R; Lei, M

2014-01-01

Objective: To investigate if cone beam CT (CBCT) can be used to estimate the delivered dose in head and neck intensity-modulated radiotherapy (IMRT). Methods: 15 patients (10 without replan and 5 with replan) were identified retrospectively. Weekly CBCT was co-registered with original planning CT. Original high-dose clinical target volume (CTV1), low-dose CTV (CTV2), brainstem, spinal cord, parotids and external body contours were copied to each CBCT and modified to account for anatomical changes. Corresponding planning target volumes (PTVs) and planning organ-at-risk volumes were created. The original plan was applied and calculated using modified per-treatment volumes on the original CT. Percentage volumetric, cumulative (planned dose delivered prior to CBCT + adaptive dose delivered after CBCT) and actual delivered (summation of weekly adaptive doses) dosimetric differences between each per-treatment and original plan were calculated. Results: There was greater volumetric change in the parotids with an average weekly difference of between −4.1% and −27.0% compared with the CTVs/PTVs (−1.8% to −5.0%). The average weekly cumulative dosimetric differences were as follows: CTV/PTV (range, −3.0% to 2.2%), ipsilateral parotid volume receiving ≥26 Gy (V26) (range, 0.5–3.2%) and contralateral V26 (range, 1.9–6.3%). In patients who required replan, the average volumetric reductions were greater: CTV1 (−2.5%), CTV2 (−6.9%), PTV1 (−4.7%), PTV2 (−11.5%), ipsilateral (−10.4%) and contralateral parotids (−12.1%), but did not result in significant dosimetric changes. Conclusion: The dosimetric changes during head and neck simultaneous integrated boost IMRT do not necessitate adaptive radiotherapy in most patients. Advances in knowledge: Our study shows that CBCT could be used for dose estimation during head and neck IMRT. PMID:24288402

Sci—Thur AM: YIS - 11: Estimation of Bladder-Wall Cumulative Dose in Multi-Fraction Image-Based Gynaecological Brachytherapy Using Deformable Point Set Registration

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

Zakariaee, R; Brown, C J; Hamarneh, G

2014-08-15

Dosimetric parameters based on dose-volume histograms (DVH) of contoured structures are routinely used to evaluate dose delivered to target structures and organs at risk. However, the DVH provides no information on the spatial distribution of the dose in situations of repeated fractions with changes in organ shape or size. The aim of this research was to develop methods to more accurately determine geometrically localized, cumulative dose to the bladder wall in intracavitary brachytherapy for cervical cancer. The CT scans and treatment plans of 20 cervical cancer patients were used. Each patient was treated with five high-dose-rate (HDR) brachytherapy fractions ofmore » 600cGy prescribed dose. The bladder inner and outer surfaces were delineated using MIM Maestro software (MIM Software Inc.) and were imported into MATLAB (MathWorks) as 3-dimensional point clouds constituting the “bladder wall”. A point-set registration toolbox for MATLAB, Coherent Point Drift (CPD), was used to non-rigidly transform the bladder-wall points from four of the fractions to the coordinate system of the remaining (reference) fraction, which was chosen to be the emptiest bladder for each patient. The doses were accumulated on the reference fraction and new cumulative dosimetric parameters were calculated. The LENT-SOMA toxicity scores of these patients were studied against the cumulative dose parameters. Based on this study, there was no significant correlation between the toxicity scores and the determined cumulative dose parameters.« less

TH-AB-207A-04: Assessment of Patients’ Cumulative Effective Dose From CT Examinations

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

Bostani, M; Cagnon, C; Sepahdari, A

Purpose: The Joint Commission requires institutions to consider patient’s age and recent imaging exams when deciding on the most appropriate type of imaging exam. Additionally, knowing patient’s imaging history can help prevent duplicate scans. Radiation dose management software affords new opportunities to identify and utilize patients with high cumulative doses as one proxy for subsequent review of imaging history and opportunities in avoiding redundant exams. Methods: Using dose management software (Radimetrics, Bayer Healthcare) a total of 72073 CT examinations performed from Jan 2015 to Jan 2016 were examined to categorize patients with a cumulative effective dose of 100 mSv andmore » above. This threshold was selected based on epidemiological studies on populations exposed to radiation, which demonstrate a statistical increase of cancer risk at doses above 100 mSv. Histories of patients with highest cumulative dose and highest number of exams were further investigated by a Radiologist for appropriateness of recurrent studies and potential opportunities for reduction. Results: Out of 34762 patients, 927 (2.7%) were identified with a cumulative dose of 100 mSv and above. The highest cumulative dose (842 mSv) belonged to an oncology patient who underwent 2 diagnostic exams and 9 interventional ablative CT guided procedures. The patient with highest number of exams (56 counts) and cumulative dose of 170 mSv was a 17 year old trauma patient. An imaging history review of these two patients did not suggest any superfluous scans. Conclusion: Our limited pilot study suggests that recurrent CT exams for patients with oncologic or severe trauma history may be warranted and appropriate. As a result, for future studies we will be focusing on high dose patient cohorts not associated with oncology or severe trauma. Additionally, the review process itself has suggested areas for potential improvement in patient care, including improved documentation and Radiologist involvement in patient management. Dr. McNitt-Gray’s disclosures: Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical Systems; Consultant, Samsung Electronics.« less

Modeling cumulative dose and exposure duration provided insights regarding the associations between benzodiazepines and injuries.

PubMed

Abrahamowicz, Michal; Bartlett, Gillian; Tamblyn, Robyn; du Berger, Roxane

2006-04-01

Accurate assessment of medication impact requires modeling cumulative effects of exposure duration and dose; however, postmarketing studies usually represent medication exposure by baseline or current use only. We propose new methods for modeling various aspects of medication use history and employment of them to assess the adverse effects of selected benzodiazepines. Time-dependent measures of cumulative dose or duration of use, with weighting of past exposures by recency, were proposed. These measures were then included in alternative versions of the multivariable Cox model to analyze the risk of fall related injuries among the elderly new users of three benzodiazepines (nitrazepam, temazepam, and flurazepam) in Quebec. Akaike's information criterion (AIC) was used to select the most predictive model for a given benzodiazepine. The best-fitting model included a combination of cumulative duration and current dose for temazepam, and cumulative dose for flurazepam and nitrazepam, with different weighting functions. The window of clinically relevant exposure was shorter for flurazepam than for the two other products. Careful modeling of the medication exposure history may enhance our understanding of the mechanisms underlying their adverse effects.

The association of rectal equivalent dose in 2 Gy fractions (EQD2) to late rectal toxicity in locally advanced cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University.

PubMed

Tharavichtikul, Ekkasit; Meungwong, Pooriwat; Chitapanarux, Taned; Chakrabandhu, Somvilai; Klunklin, Pitchayaponne; Onchan, Wimrak; Wanwilairat, Somsak; Traisathit, Patrinee; Galalae, Razvan; Chitapanarux, Imjai

2014-06-01

To evaluate association between equivalent dose in 2 Gy (EQD2) to rectal point dose and gastrointestinal toxicity from whole pelvic radiotherapy (WPRT) and intracavitary brachytherapy (ICBT) in cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University. Retrospective study was designed for the patients with locally advanced cervical cancer, treated by radical radiotherapy from 2004 to 2009 and were evaluated by rectosigmoidoscopy. The cumulative doses of WPRT and ICBT to the maximally rectal point were calculated to the EQD2 and evaluated the association of toxicities. Thirty-nine patients were evaluated for late rectal toxicity. The mean cumulative dose in term of EQD2 to rectum was 64.2 Gy. Grade 1 toxicities were the most common findings. According to endoscopic exam, the most common toxicities were congested mucosa (36 patients) and telangiectasia (32 patients). In evaluation between rectal dose in EQD2 and toxicities, no association of cumulative rectal dose to rectal toxicity, except the association of cumulative rectal dose in EQD2 >65 Gy to late effects of normal tissue (LENT-SOMA) scale ≥ grade 2 (p = 0.022; odds ratio, 5.312; 95% confidence interval, 1.269-22.244). The cumulative rectal dose in EQD2 >65 Gy have association with ≥ grade 2 LENT-SOMA scale.

The association of rectal equivalent dose in 2 Gy fractions (EQD2) to late rectal toxicity in locally advanced cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University

PubMed Central

Meungwong, Pooriwat; Chitapanarux, Taned; Chakrabandhu, Somvilai; Klunklin, Pitchayaponne; Onchan, Wimrak; Wanwilairat, Somsak; Traisathit, Patrinee; Galalae, Razvan; Chitapanarux, Imjai

2014-01-01

Purpose To evaluate association between equivalent dose in 2 Gy (EQD2) to rectal point dose and gastrointestinal toxicity from whole pelvic radiotherapy (WPRT) and intracavitary brachytherapy (ICBT) in cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University. Materials and Methods Retrospective study was designed for the patients with locally advanced cervical cancer, treated by radical radiotherapy from 2004 to 2009 and were evaluated by rectosigmoidoscopy. The cumulative doses of WPRT and ICBT to the maximally rectal point were calculated to the EQD2 and evaluated the association of toxicities. Results Thirty-nine patients were evaluated for late rectal toxicity. The mean cumulative dose in term of EQD2 to rectum was 64.2 Gy. Grade 1 toxicities were the most common findings. According to endoscopic exam, the most common toxicities were congested mucosa (36 patients) and telangiectasia (32 patients). In evaluation between rectal dose in EQD2 and toxicities, no association of cumulative rectal dose to rectal toxicity, except the association of cumulative rectal dose in EQD2 >65 Gy to late effects of normal tissue (LENT-SOMA) scale ≥ grade 2 (p = 0.022; odds ratio, 5.312; 95% confidence interval, 1.269-22.244). Conclusion The cumulative rectal dose in EQD2 >65 Gy have association with ≥ grade 2 LENT-SOMA scale. PMID:25061573

Early cumulative risk predicts externalizing behavior at age 10: The mediating role of adverse parenting.

PubMed

Gach, Emily J; Ip, Ka I; Sameroff, Arnold J; Olson, Sheryl L

2018-02-01

Multiple environmental risk factors in early childhood predict a broad range of adverse developmental outcomes. However, most prior longitudinal research has not illuminated explanatory mechanisms. Our main goals were to examine predictive associations between cumulative ecological risk factors in early childhood and children's later externalizing problems and to determine whether these associations were explained by variations in parenting quality. Participants were 241 children (118 girls) at risk for school-age conduct problems and their parents and teachers. Children were approximately 3 years old at Time 1 (T1) and 10 years old at Time 2 (T2). Reports of contextual risk at T1 were used to develop a cumulative risk index consisting of 6 singular risk variables from 3 ecological levels: social resources (low income; social isolation), family resources (marital aggression; poor total family functioning), and maternal resources (single parent status; poor maternal mental health). At T1, parenting variables were measured (corporal punishment, warm responsiveness, maternal efficacy, and negative perceptions of child behavior). At T2, mothers, fathers, and teachers reported child externalizing problems. Johnson's relative weight analysis revealed that the cumulative risk index was a more powerful predictor of age 10 years externalizing behavior than any of the singular contextual risk variables. Adverse parenting mediated the effects of cumulative risk on later child externalizing problems. Our findings have significant implications for understanding long-term effects of multiple contextual risk factors present in early childhood and for the implementation of positive parenting interventions early on. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Multiple Testing, Cumulative Radiation Dose, and Clinical Indications in Patients Undergoing Myocardial Perfusion Imaging

PubMed Central

Einstein, Andrew J.; Weiner, Shepard D.; Bernheim, Adam; Kulon, Michal; Bokhari, Sabahat; Johnson, Lynne L.; Moses, Jeffrey W.; Balter, Stephen

2013-01-01

Context Myocardial perfusion imaging (MPI) is the single medical test with the highest radiation burden to the US population. While many patients undergoing MPI receive repeat MPI testing, or additional procedures involving ionizing radiation, no data are available characterizing their total longitudinal radiation burden and relating radiation burden with reasons for testing. Objective To characterize procedure counts, cumulative estimated effective doses of radiation, and clinical indications, for patients undergoing MPI. Design, Setting, Patients Retrospective cohort study evaluating, for 1097 consecutive patients undergoing index MPI during the first 100 days of 2006 at Columbia University Medical Center, all preceding medical imaging procedures involving ionizing radiation undergone beginning October 1988, and all subsequent procedures through June 2008, at that center. Main Outcome Measures Cumulative estimated effective dose of radiation, number of procedures involving radiation, and indications for testing. Results Patients underwent a median (interquartile range, mean) of 15 (6–32, 23.9) procedures involving radiation exposure; 4 (2–8, 6.5) were high-dose (≥3 mSv, i.e. one year's background radiation), including 1 (1–2, 1.8) MPI studies per patient. 31% of patients received cumulative estimated effective dose from all medical sources >100mSv. Multiple MPIs were performed in 39% of patients, for whom cumulative estimated effective dose was 121 (81–189, 149) mSv. Men and whites had higher cumulative estimated effective doses, and there was a trend towards men being more likely to undergo multiple MPIs than women (40.8% vs. 36.6%, Odds ratio 1.29, 95% confidence interval 0.98–1.69). Over 80% of initial and 90% of repeat MPI exams were performed in patients with known cardiac disease or symptoms consistent with it. Conclusion In this institution, multiple testing with MPI was very common, and in many patients associated with very high cumulative estimated doses of radiation. PMID:21078807

Repeated exposure to high-frequency spanking and child externalizing behavior across the first decade: a moderating role for cumulative risk.

PubMed

MacKenzie, Michael J; Nicklas, Eric; Brooks-Gunn, Jeanne; Waldfogel, Jane

2014-12-01

This study used the Fragile Families and Child Well-Being Study to examine the effects of repeated exposure to harsh parenting on child externalizing behavior across the first decade of life, and a moderating role for cumulative ecological risk. Maternal report of harsh parenting, defined as high frequency spanking, was assessed at age 1, 3, 5, and 9, along with child externalizing at age 9 (N=2,768). Controlling for gender, race, maternal nativity, and city of residence, we found a cumulative risk index to significantly moderate the effects of repeated harsh parenting on child behavior, with the effects of repeated high-frequency spanking being amplified for those experiencing greater levels of cumulative risk. Harsh parenting, in the form of high frequency spanking, remains a too common experience for children, and results demonstrate that the effects of repeated exposure to harsh parenting across the first decade are amplified for those children already facing the most burden. Copyright © 2014. Published by Elsevier Ltd.

Repeated exposure to high-frequency spanking and child externalizing behavior across the first decade: A moderating role for cumulative risk

PubMed Central

MacKenzie, Michael J.; Nicklas, Eric; Brooks-Gunn, Jeanne; Waldfogel, Jane

2016-01-01

This study used the Fragile Families and Child Well-being study to examine the effects of repeated exposure to harsh parenting on child externalizing behavior across the first decade of life, and a moderating role for cumulative ecological risk. Maternal report of harsh parenting, defined as high frequency spanking, was assessed at age 1, 3, 5, and 9, along with child externalizing at age 9 (N=2768). Controlling for gender, race, maternal nativity, and city of residence, we found a cumulative risk index to significantly moderate the effects of repeated harsh parenting on child behavior, with the effects of repeated high-frequency spanking being amplified for those experiencing greater levels of cumulative risk. Harsh parenting, in the form of high frequency spanking, remains a too common experience for children, and results demonstrate that the effects of repeated exposure to harsh parenting across the first decade are amplified for those children already facing the most burden. PMID:25465318

Cumulative doses analysis in young trauma patients: a single-centre experience.

PubMed

Salerno, Sergio; Marrale, Maurizio; Geraci, Claudia; Caruso, Giuseppe; Lo Re, Giuseppe; Lo Casto, Antonio; Midiri, Massimo

2016-02-01

Multidetector computed tomography (MDCT) represents the main source of radiation exposure in trauma patients. The radiation exposure of young patients is a matter of considerable medical concern due to possible long-term effects. Multiple MDCT studies have been observed in the young trauma population with an increase in radiation exposure. We have identified 249 young adult patients (178 men and 71 women; age range 14-40 years) who had received more than one MDCT study between June 2010 and June 2014. According to the International Commission on Radiological Protection publication, we have calculated the cumulative organ dose tissue-weighting factors by using CT-EXPO software(®). We have observed a mean cumulative dose of about 27 mSv (range from 3 to 297 mSv). The distribution analysis is characterised by low effective dose, below 20 mSv, in the majority of the patients. However, in 29 patients, the effective dose was found to be higher than 20 mSv. Dose distribution for the various organs analysed (breasts, ovaries, testicles, heart and eye lenses) shows an intense peak for lower doses, but in some cases high doses were recorded. Even though cumulative doses may have long-term effects, which are still under debate, high doses are observed in this specific group of young patients.

Higher-order spin-noise spectroscopy of atomic spins in fluctuating external fields

DOE PAGES

Li, Fuxiang; Crooker, S. A.; Sinitsyn, N. A.

2016-03-09

Here, we discuss the effect of external noisy magnetic fields on mesoscopic spin fluctuations that can be probed in semiconductors and atomic vapors by means of optical spin-noise spectroscopy. We also show that conventional arguments of the law of large numbers do not apply to spin correlations induced by external fields, namely, the magnitude of the 4th-order spin cumulant grows as ~N 2 with the number N of observed spins, i.e., it is not suppressed in comparison to the 2nd-order cumulant. Moreover, this allows us to design a simple experiment to measure the 4th-order cumulant of spin fluctuations in anmore » atomic system near thermodynamic equilibrium and develop a quantitative theory that explains all observations.« less

Nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) in pediatric and young adult patients: Results from a prospective study using limited-margin radiotherapy.

PubMed

Tinkle, Christopher L; Fernandez-Pineda, Israel; Sykes, April; Lu, Zhaohua; Hua, Chia-Ho; Neel, Michael D; Bahrami, Armita; Shulkin, Barry L; Kaste, Sue C; Pappo, Alberto; Spunt, Sheri L; Krasin, Matthew J

2017-11-15

Indications for and delivery of adjuvant therapies for pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) have been derived largely from adult studies; therefore, significant concern remains regarding radiation exposure to normal tissue. The authors report long-term treatment outcomes and toxicities for pediatric and young adult patients with high-grade NRSTS who were treated on a prospective trial using limited-margin radiotherapy. Sixty-two patients (ages 3-22 years) with predominantly high-grade NRSTS requiring radiation were treated on a phase 2 institutional study of conformal external-beam radiotherapy and/or brachytherapy using a 1.5-cm to 2-cm anatomically constrained margin. The estimated cumulative incidence of local failure, Gray's method estimated cumulative incidence of local failure, Kaplan-Meier method estimated survival, competing-risk regression model determined predictors of disease outcome, and toxicity was reported according to CTCAE v2.0. At a median follow-up of 5.1 years (range, 0.2-10.9 years), 9 patients had experienced local failure. The 5-year overall cumulative incidence of local failure was 14.8% (95% confidence interval [CI], 7.2%-25%), and all but 1 local failure occurred outside the highest-dose irradiation volume. The 5-year Kaplan-Meier estimates for event-free and overall survival were 49.3% (95% CI, 36.3%-61.1%) and 67.9% (95% CI, 54.2%-78.3%), respectively. Multivariable analysis indicated that younger age was the only independent predictor of local recurrence (P = .004). The 5-year cumulative incidence of grade 3 or 4 late toxicity was 15% (95% CI, 7.2%-25.3%). The delivery of limited-margin radiotherapy using conformal external-beam radiotherapy or brachytherapy provides a high rate of local tumor control without an increase in marginal failures and with acceptable treatment-related morbidity. Cancer 2017;123:4419-29. © 2017 American Cancer Society. © 2017 American Cancer Society.

Experimental measurements and Monte Carlo simulations of dose perturbation around a nonradioactive brachytherapy seed due to 6- and 18-MV photons.

PubMed

Steinman, James Paul; Bakhtiari, Mohammad; Malhotra, Harish Kumar

2012-01-01

Radioactive seeds used in permanent prostate brachytherapy are composed of high-Z metals and may exceed 100 in a patient. If supplemental external beam treatment is administered afterward, the seeds may cause substantial dose perturbation, which is being investigated in this article. Film measurements using 6-MV beam were primarily carried out using Kodak XV2 film layered above and below a nonradioactive iodine-125 ((125)I) seed. Monte Carlo simulations were carried out using DOSXYZnrc. Other experimental comparisons looked at changing beam energy, depth, and field size, including two opposing fields' pair. Effect of multiple seeds spatially spaced 0.5cm vertically was also studied. For a single (125)I seed, on XV film, there is a localized dose enhancement of 6.3% upstream and -10.9% downstream. With two opposing fields, a cold spot around the seed of ∼3% was noticed. Increasing beam energy and field size decreased the magnitude of this effect, whereas the effect was found to increase with the increasing Z of material. DOSXYZnrc and EBT-2 film verified maximum dose enhancement of +15% upstream and -20% downstream of the (125)I seed surface. In general, the dose perturbation because of the seeds was spatially limited to ∼2mm upstream and ∼5mm downstream to the incident beam. Similar to other heterogeneities, the seeds perturbation depends on incident beam energy, field size, and its Z. With multiple seeds spatially apart and multiple radiation fields routinely used in external beam radiotherapy, the cumulative effect may not result in clinically significant dose perturbation. Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Survey of patient dosimetry for head and neck cancer patients undergoing external radiotherapy treatment: a study from northeastern hospitals of India.

PubMed

Sharma, Arunkumar B; Singh, Tomcha Th; Singh, Khelendra N; Gartia, R K

2009-01-01

To study dosimetry of patients during the external radiotherapy of head and neck cancers from different hospitals of the northeastern region (NER) of India. 35 confirmed cases of head and neck cancers reporting to three different hospitals in the NER of India who underwent radiation treatment were the materials for the study. Dosimetry was carried out at 8(eight) anatomical points to these patients, namely, target (entrance and exit points), forehead, chest, abdomen, gonad, arm, and leg respectively by thermoluminescence (TL) as well as optically stimulated luminescence (OSL) dosimeters. Unlike conventional appliances, we used common iodized salt as TL/OSL phosphor. Patient dosimetry was found to vary with an average of 1.17 +/- 0.39 Sv at forehead, 1.24 +/- 0.39 Sv at chest, 0.52 +/- 0.13 Sv at gonad to a minimum of 0.26 +/- 0.07 Sv at leg areas when exposed to a cumulative dose of 65 Sv at the target. Maximum dose received from a stray radiation is about 1.5 Sv at forehead/chest and dosimetry of patient among the three centers is not significantly different at the 5% level of probability.

Lead in teeth from lead-dosed goats: Microdistribution and relationship to the cumulative lead dose

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

Bellis, David J.; Hetter, Katherine M.; Jones, Joseph

2008-01-15

Teeth are commonly used as a biomarker of long-term lead exposure. There appear to be few data, however, on the content or distribution of lead in teeth where data on specific lead intake (dose) are also available. This study describes the analysis of a convenience sample of teeth from animals that were dosed with lead for other purposes, i.e., a proficiency testing program for blood lead. Lead concentration of whole teeth obtained from 23 animals, as determined by atomic absorption spectrometry, varied from 0.6 to 80 {mu}g g{sup -1}. Linear regression of whole tooth lead ({mu}g g{sup -1}) on themore » cumulative lead dose received by the animal (g) yielded a slope of 1.2, with r{sup 2}=0.647 (p<0.0001). Laser ablation inductively coupled plasma mass spectrometry was employed to determine lead content at micrometer scale spatial resolution in the teeth of seven goats representing the dosing range. Highly localized concentrations of lead, ranging from about 10 to 2000 {mu}g g{sup -1}, were found in circumpulpal dentine. Linear regression of circumpulpal lead ({mu}g g{sup -1}) on cumulative lead dose (g) yielded a slope of 23 with r{sup 2}=0.961 (p=0.0001). The data indicated that whole tooth lead, and especially circumpulpal lead, of dosed goats increased linearly with cumulative lead exposure. These data suggest that circumpulpal dentine is a better biomarker of cumulative lead exposure than is whole tooth lead, at least for lead-dosed goats.« less

Brain injury and development in preterm infants exposed to fentanyl

PubMed Central

McPherson, Christopher; Haslam, Matthew; Pineda, Roberta; Rogers, Cynthia; Neil, Jeffrey J.; Inder, Terrie E.

2015-01-01

Background Fentanyl is commonly utilized in preterm infants. Relatively little is known regarding the neurodevelopmental outcomes of preterm infants exposed to fentanyl. Objective To investigate the association between cumulative fentanyl dose and brain injury and diameters in a cohort of preterm infants Methods Data on demographics, perinatal course, and neonatal course, including total fentanyl exposure prior to term equivalent age, were retrospectively evaluated for 103 infants born at ≤ 30 weeks gestational age who underwent magnetic resonance imaging at term equivalent age (mean gestational age 26.9 ± 1.8 weeks). Magnetic resonance images were evaluated for brain injury and regional brain diameters. Developmental testing was conducted at term equivalent and 2 years of age. Results Seventy-eight infants (76%) received fentanyl (median cumulative dose 3 μg/kg, interquartile range 1 – 441 μg/kg). Cumulative fentanyl dose in the first week of life correlated with the incidence of cerebellar hemorrhage after correction for covariates (OR 2.1, 95% confidence interval 1.1 – 4.1). Cumulative fentanyl dose before term equivalent age correlated with reductions in transverse cerebellar diameter after correction for covariates including the presence of cerebellar hemorrhage (r = 0.461, p = 0.002). No correlation was detected between cumulative fentanyl dose and development at 2 years of age. Conclusions Higher cumulative fentanyl dose in preterm infants correlated with a higher incidence of cerebellar injury and lower cerebellar diameter at term equivalent age. Our findings must be taken with caution, but emphasize the need for future prospective trials examining the risks and benefits of commonly utilized analgesic agents in preterm infants. PMID:26369570

Methadone and Metabolites in Hair of Methadone-Assisted Pregnant Women and Their Infants

PubMed Central

Himes, Sarah K; Goodwin, Robert S; Rock, Colleen M; Jones, Hendrée E; Johnson, Rolley E; Wilkins, Diana G; Huestis, Marilyn A

2012-01-01

Methadone is the recommended pharmacotherapy for opioid-dependent pregnant women. The primary aims of this study were to determine whether a dose-concentration relationship exists between cumulative maternal methadone dose, methadone and metabolite concentrations in maternal hair during pregnancy and whether maternal hair methadone and metabolite concentrations predict neonatal outcomes. Materials and Methods Hair specimens were collected monthly from opioid-dependent mothers enrolled in methadone treatment and 4 of their infants. Hair specimens were segmented (3cm), washed (maternal hair only) and analyzed for methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyrroline (EMDP) by liquid chromatography tandem mass spectrometry. Results There was large inter-subject variability and no dose-concentration relationship for cumulative methadone dose and methadone, EDDP, EMDP or total concentrations in hair. For individual women, a positive trend was noted for cumulative methadone dose and methadone and EDDP concentrations in hair. There was a positive linear trend for cumulative methadone dose and EDDP/methadone ratio in maternal hair, perhaps reflecting methadone’s induction of its own metabolism. Maternal methadone concentrations were higher than those in infant hair, and infant EDDP hair concentrations were higher than those in maternal hair. Maternal methadone dose, and methadone and EDDP hair concentrations were not correlated with peak infant neonatal abstinence syndrome (NAS) scores, days to peak NAS, duration of NAS, time to NAS onset, birth length, head circumference or amount of neonatal morphine pharmacotherapy. Maternal cumulative 3rd trimester methadone dose was positively correlated with infant birth weight. Conclusion Methadone and EDDP in pregnant women’s hair are markers of methadone exposure and do not predict total methadone dose, nor neonatal outcomes from in utero methadone exposure. PMID:22495425

Eye lens radiation exposure to interventional cardiologists: a retrospective assessment of cumulative doses.

PubMed

Jacob, Sophie; Donadille, Laurent; Maccia, Carlo; Bar, Olivier; Boveda, Serge; Laurier, Dominique; Bernier, Marie-Odile

2013-03-01

Radiation dose to the eye lens is a crucial issue for interventional cardiologists (ICs) who are exposed during the procedures they perform. This paper presents a retrospective assessment of the cumulative eye lens doses of ICs enrolled in the O'CLOC study for Occupational Cataracts and Lens Opacities in interventional Cardiology. Information on the workload in the catheterisation laboratory, radiation protection equipment, eye lens dose per procedure and dose reduction factors associated with eye-protective equipment were considered. For the 129 ICs at an average age of 51 who had worked for an average period of 22 years, the estimated cumulative eye lens dose ranged from 25 mSv to more than 1600 mSv; the mean ± SD was 423 ± 359 mSv. After several years of practice, without eye protection, ICs may exceed the new ICRP lifetime eye dose threshold of 500 mSv and be at high risk of developing early radiation-induced cataracts. Radiation protection equipment can reduce these doses and should be used routinely.

Long-term cardiac (valvulopathy) safety of cabergoline in prolactinoma

PubMed Central

Khare, Shruti; Lila, Anurag R.; Patil, Rishikesh; Phadke, Milind; Kerkar, Prafulla; Bandgar, Tushar; Shah, Nalini S.

2017-01-01

Background: Clinical relevance of association of cabergoline use for hyperprolactinemia and cardiac valvulopathy remains unclear. Objective: The aim of the study was to determine the prevalence of valvular heart abnormalities in patients taking cabergoline for the treatment of prolactinoma and to explore any associations with the cumulative dose of drug used. Design: A cross-sectional echocardiographic study was performed in patients who were receiving cabergoline therapy for prolactinoma. Results: Hundred (61 females, 39 males) prolactinoma cases (81 macroprolactinoma and 19 microprolactinoma) were included in the study. The mean age at presentation was 33.9 ± 9.0 years (range: 16–58 years). The mean duration of treatment was 53.11 ± 43.15 months (range: 12–155 months). The mean cumulative dose was 308.6 ± 290.2 mg (range: 26–1196 mg; interquartile range: 104–416 mg). Mild mitral regurgitation was present in one patient (cumulative cabergoline dose 104 mg). Mild tricuspid regurgitation was present in another two patients (cumulative cabergoline dose 52 mg and 104 mg). Aortic and pulmonary valve functioning was normal in all the cases. There were no cases of significant valvular regurgitation (moderate to severe, Grade 3–4). None of the patients had morphological abnormalities such as thickening, calcification, and restricted mobility of any of the cardiac valves. Conclusion: Cabergoline appears to be safe in patients with prolactinoma up to the cumulative dose of ~300 mg. The screening for valvulopathy should be restricted to those with higher cumulative cabergoline exposure. PMID:28217516

Cumulative effects from repeated exposures to ultraviolet radiation

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

Kaidbey, K.H.; Kligman, A.M.

Repeated exposures to subliminal doses of UVR, given at 24-hr intervals, resulted in a lowering of the erythema threshold dose. At erythemogenically equivalent doses, UV-A was the most effective and UV-C the least. A similar and more pronounced effect was observed following repeated exposures to subthreshold doses of UV-A and topically applied 8-methoxypsoralen. These findings provide quantitative evidence for the cumulative nature of acute UVR damage in human skin.

Esophagus cancer and radiation exposure due to nuclear test fallout: an analysis based on the data of the Semipalatinsk historical cohort, 1960-1999.

PubMed

Bauer, S; Gusev, B I; Pivina, L M; Apsalikov, K N; Grosche, B

2006-01-01

This paper describes the Semipalatinsk historical cohort study and, in particular, examines the association between combined external and internal radiation exposure and esophagus cancer. Esophagus cancer is the most frequent single cancer site in the cause of death follow-up for the Semipalatinsk cohort. Set up in the 1960s, this historical cohort included 10 exposed settlements in the vicinity of the Semipalatinsk nuclear test site in East Kazakhstan as well as 6 comparison settlements in a low exposure area of the same region. The external and internal radiation doses to the population of the settlements under study were mainly due to local fallout from atmospheric nuclear testing (1949-1962). The database includes dosimetry and health information for 19.545 inhabitants of exposed and comparison villages in the Semipalatinsk region, comprising a total of 582.750 person-years of follow-up between 1960 and 1999. Cumulative effective dose estimates in this cohort range from 20 mSv to -4 Sv, with a mean dose of 634 mSv in the exposed group. Relative risks were calculated in terms of rate ratios, using a Poisson regression model for grouped person-time data. Esophagus cancer was found substantially elevated, with a statistically significant increase of the relative risk with dose and an ERR/Sv of 2.37 (1.45; 3.28) for the total cohort. If the data set was restricted to the exposed group only, the ERR/Sv was found considerably lower (0.18 (-0.16; 0.52)), whereas the dose-response remained significant only in women. Overall, our results based on the Semipalatinsk historical cohort indicate an association between fallout exposure and the risk of esophagus cancer that should be further investigated.

Eye Lens Opacities Among Physicians Occupationally Exposed to Ionizing Radiation.

PubMed

Auvinen, Anssi; Kivelä, Tero; Heinävaara, Sirpa; Mrena, Samy

2015-08-01

We compared the frequency of lens opacities among physicians with and without occupational exposure to ionizing radiation, and estimated dose-response between cumulative dose and opacities. We conducted ophthalmologic examinations of 21 physicians with occupational exposure to radiation and 16 unexposed physicians. Information on cumulative radiation doses (mean 111 mSv) was based on dosimeter readings recorded in a national database on occupational exposures. Lens changes were evaluated using the Lens Opacities Classification System II, with an emphasis on posterior subcapsular (PSC) and cortical changes. Among the exposed physicians, the prevalences of cortical and PSC changes were both 11% (3/21), and the corresponding frequencies in the unexposed group were 44% (n = 7) and 6% (n = 1). For dose-response analysis, the data were pooled with 29 exposed physicians from our previous study. No association of either type of lens changes with cumulative recorded dose was observed. Our findings do not indicate an increased frequency of lens opacities in physicians with occupational exposure to ionizing radiation. However, the subjects in this study have received relatively low doses and therefore the results do not exclude small increases in lens opacities or contradict the studies reporting increases among interventional cardiologists with materially higher cumulative doses. © The Author 2015. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

The injury and cumulative effects on human skin by UV exposure from artificial fluorescence emission.

PubMed

Tian, Yan; Liu, Wei; Niu, TianHui; Dai, CaiHong; Li, Xiaoxin; Cui, Caijuan; Zhao, Xinyan; E, Yaping; Lu, Hui

2014-01-01

The injury and cumulative effects of UV emission from fluorescence lamp were studied. UV intensity from fluorescence lamp was measured, and human skin samples (hips, 10 volunteers) were exposed to low-dose UV irradiation (three times per week for 13 consecutive weeks). Three groups were examined: control group without UV radiation; low-dose group with a cumulative dose of 50 J cm(-2) which was equivalent to irradiation of the face during indoor work for 1.5 years; and high-dose group with 1000 J cm(-2) cumulative dose equivalent to irradiation of the face during outdoor activities for 1 year. Specific indicators were measured before and after UVA irradiation. The findings showed that extending the low-dose UVA exposure decreased the skin moisture content and increased the transepidermal water loss as well as induced skin color changes (decreased L* value, increased M index). Furthermore, irradiated skin showed an increased thickness of cuticle and epidermis, skin edema, light color and unclear staining collagen fibers in the dermis, and elastic fiber fragmentation. In addition, MMP-1, p53 and SIRT1 expression was also increased. Long-term exposure of low-dose UVA radiation enhanced skin photoaging. The safety of the fluorescent lamp needs our attention. © 2014 The American Society of Photobiology.

Cumulative childhood maltreatment and its dose-response relation with adult symptomatology: Findings in a sample of adult survivors of sexual abuse.

PubMed

Steine, Iris M; Winje, Dagfinn; Krystal, John H; Bjorvatn, Bjørn; Milde, Anne Marita; Grønli, Janne; Nordhus, Inger Hilde; Pallesen, Ståle

2017-03-01

In the present study, we examined the role of cumulative childhood maltreatment experiences for several health related outcomes in adulthood, including symptoms of psychological distress as well as perceived social support and hardiness. The sample comprised adult survivors of sexual abuse (N=278, 95.3% women, mean age at first abusive incident=6.4 years). One-way ANOVAs revealed a statistically significant dose-response relation between cumulative childhood maltreatment scores and self-reported symptoms of posttraumatic stress (PTSS), anxiety, depression, eating disorders, dissociation, insomnia, nightmare related distress, physical pain, emotional pain, relational problems, self-harm behaviors as well as on a measure of symptom complexity. Cumulative childhood maltreatment was also associated with lower levels of work functioning. An inverse dose-response relation was found for perceived social support and hardiness. Using a Bonferroni corrected alpha level, cumulative childhood maltreatment remained significantly associated with all outcome measures with the exception of eating disorder symptoms after controlling for abuse-related independent variables in hierarchical regression analyses. Results add to previous literature by showing that dose-response relation between cumulative childhood adversities and adult symptom outcomes could also be identified in a sample characterized by high exposure to adversities, and lends support to the notion put forth by previous authors that cumulative childhood adversities seem to be related to the severity of adult health outcomes in a rule-governed way. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lung Cancer Risk from Plutonium: A Pooled Analysis of the Mayak and Sellafield Worker Cohorts.

PubMed

Gillies, Michael; Kuznetsova, Irina; Sokolnikov, Mikhail; Haylock, Richard; O'Hagan, Jackie; Tsareva, Yulia; Labutina, Elena

2017-12-01

In this study, lung cancer risk from occupational plutonium exposure was analyzed in a pooled cohort of Mayak and Sellafield workers, two of the most informative cohorts in the world with detailed plutonium urine monitoring programs. The pooled cohort comprised 45,817 workers: 23,443 Sellafield workers first employed during 1947-2002 with follow-up until the end of 2005 and 22,374 Mayak workers first employed during 1948-1982 with follow-up until the end of 2008. In the pooled cohort 1,195 lung cancer deaths were observed (789 Mayak, 406 Sellafield) but only 893 lung cancer incidences (509 Mayak, 384 Sellafield, due to truncated follow-up in the incidence analysis). Analyses were performed using Poisson regression models, and were based on doses derived from individual radiation monitoring data using an updated dose assessment methodology developed in the study. There was clear evidence of a linear association between cumulative internal plutonium lung dose and risk of both lung cancer mortality and incidence in the pooled cohort. The pooled point estimates of the excess relative risk (ERR) from plutonium exposure for both lung cancer mortality and incidence were within the range of 5-8 per Gy for males at age 60. The ERR estimates in relationship to external gamma radiation were also significantly raised and in the range 0.2-0.4 per Gy of cumulative gamma dose to the lung. The point estimates of risk, for both external and plutonium exposure, were comparable between the cohorts, which suggests that the pooling of these data was valid. The results support point estimates of relative biological effectiveness (RBE) in the range of 10-25, which is in broad agreement with the value of 20 currently adopted in radiological protection as the radiation weighting factor for alpha particles, however, the uncertainty on this value (RBE = 21; 95% CI: 9-178) is large. The results provide direct evidence that the plutonium risks in each cohort are of the same order of magnitude but the uncertainty on the Sellafield cohort plutonium risk estimates is large, with observed risks consistent with no plutonium risk, and risks five times larger than those observed in the Mayak cohort.

Ionizing diagnostic radiation exposure in patients with Crohn's disease: A retrospective study in a medium hospital and its predictive factors.

PubMed

Merino Rodríguez, Esther; Carrera Alonso, Elisa; Torralba González de Suso, Miguel; Sánchez da Silva, Marta; Martínez López, María; Sánchez-Tembleque Zarandona, María Dolores

2018-02-01

It is estimated that diagnostic medical radiation exposure may be responsable for 0.5-2% of cancers worldwide. Because of the relapsing course of Crohn's disease (CD), these patients usually requiere multiple ionizing radiation test. Stimating the total cumulative effective dose received by our CD patients and identifying the risk factors associated with the exposure to a cumulative effective dose due to the disease (CEED) > 50mSv. Retrospective cohort study (2001-2014). patients with CD. Risk dose >50mSv. For calculating de cumulative effective dose and the CEED, all the ionizing test done were taken. For identifying predictive factors for receiving a CEDD >50mSv, an univariate and a multivariate logistic regression analyses were performed using a >50mSv dose as dependent variable. Of the 267 patients analyzed the 24.6% of them received a cumulative effective dose > 50mSv and the 15.2% a CEED>50mSv. In the multivariate analysis, the following variables were identified as independent predictors associated with a CEDD >50mSv: major surgery (OR= 2.1; IC 95% [1.1-3.8]; p=.019) and severity (OR= 20.6; IC 95% [4.5-94.8]; p<.01). Patients with CD are more at risk of receiving risk CEED, so it would be advisable to monitor the cumulative effective dose received to anticipate our intervention in order to avoid reaching that dose. The ultrasounds and abdominal resonance enterography are alternatives in these cases, although their accessibility is limited in some centers. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Dose-Response Relationship between Cumulative Occupational Lead Exposure and the Associated Health Damages: A 20-Year Cohort Study of a Smelter in China

PubMed Central

Wu, Yue; Gu, Jun-Ming; Huang, Yun; Duan, Yan-Ying; Huang, Rui-Xue; Hu, Jian-An

2016-01-01

Long-term airborne lead exposure, even below official occupational limits, has been found to cause lead poisoning at higher frequencies than expected, which suggests that China’s existing occupational exposure limits should be reexamined. A retrospective cohort study was conducted on 1832 smelting workers from 1988 to 2008 in China. These were individuals who entered the plant and came into continuous contact with lead at work for longer than 3 months. The dose-response relationship between occupational cumulative lead exposure and lead poisoning, abnormal blood lead, urinary lead and erythrocyte zinc protoporphyrin (ZPP) were analyzed and the benchmark dose lower bound confidence limits (BMDLs) were calculated. Statistically significant positive correlations were found between cumulative lead dust and lead fumes exposures and workplace seniority, blood lead, urinary lead and ZPP values. A dose-response relationship was observed between cumulative lead dust or lead fumes exposure and lead poisoning (p < 0.01). The BMDLs of the cumulative occupational lead dust and fumes doses were 0.68 mg-year/m3 and 0.30 mg-year/m3 for lead poisoning, respectively. The BMDLs of workplace airborne lead concentrations associated with lead poisoning were 0.02 mg/m3 and 0.01 mg/m3 for occupational exposure lead dust and lead fume, respectively. In conclusion, BMDLs for airborne lead were lower than occupational exposure limits, suggesting that the occupational lead exposure limits need re-examination and adjustment. Occupational cumulative exposure limits (OCELs) should be established to better prevent occupational lead poisoning. PMID:26999177

Biokinetics and dosimetry of several radiolabelled peptides in cancer cells

NASA Astrophysics Data System (ADS)

Rodríguez-Cortés, J.; Ferro-Flores, G.; de Murphy, C. Arteaga; Pedraza-López, M.; Ramírez-Iglesias, M. A. T.

Radiolabelled peptides have been used as target-specific radiopharmaceuticals. The goal of this research was the in vitro assessment of the uptake, internalization, externalization, and efflux of five radiolabelled peptides in cancer cells to estimate radiation-absorbed doses from experimental biokinetic data. 177Lu-DOTA-octreotate, 188Re-lanreotide, and 99mTc-HYNIC-octreotide were studied in the AR42J cell line. The PC3 and NCIH69 cells were used for 99mTc-HYNIC-bombesin and 177Lu-DOTA-minigastrin, respectively. The cumulated activities in the membrane and cytoplasm were calculated by integration of the experimental time-activity curves and used for dosimetry calculations according to the Medical Internal Radiation Dose (MIRD) cellular methodology. The mean absorbed dose to the cell nucleus were 0.69±0.09, 0.11±0.08, 0.55±0.09, 3.45±0.48, and 3.30±0.65 Gy/Bq for 99mTc-HYNIC-bombesin, 99mTc-HYNIC-octreotide, 177Lu-DOTA-minigastrin, 177Lu-DOTA-octreotate, and 188Re-lanreotide, respectively. If radiopharmaceutical cell kinetics were not used and only uptake data were considered, the calculated doses would be overestimated up to 25 times.

Patterns of prednisone use during pregnancy in women with rheumatoid arthritis: Daily and cumulative dose.

PubMed

Palmsten, Kristin; Rolland, Matthieu; Hebert, Mary F; Clowse, Megan E B; Schatz, Michael; Xu, Ronghui; Chambers, Christina D

2018-04-01

To characterize prednisone use in pregnant women with rheumatoid arthritis using individual-level heat-maps and clustering individual trajectories of prednisone dose, and to evaluate the association between prednisone dose trajectory groups and gestational length. This study included pregnant women with rheumatoid arthritis who enrolled in the MotherToBaby Autoimmune Diseases in Pregnancy Study (2003-2014) before gestational week 20 and reported prednisone use without another oral glucocorticoid during pregnancy (n = 254). Information on medication use and pregnancy outcomes was collected by telephone interview plus by medical record review. Prednisone daily dose and cumulative dose were plotted by gestational day using a heat map for each individual. K-means clustering was used to cluster individual trajectories of prednisone dose into groups. The associations between trajectory group and demographics, disease severity measured by the Health Assessment Questionnaire at enrollment, and gestational length were evaluated. Women used prednisone 3 to 292 days during pregnancy, with daily doses ranging from <1 to 60 mg. Total cumulative dose ranged from 8 to 6225 mg. Disease severity, non-biologic disease modifying anti-rheumatic drug use, and gestational length varied significantly by trajectory group. After adjusting for disease severity, non-biologic disease modifying anti-rheumatic drug use, and other covariates, the highest vs lowest daily dose trajectory group was associated with reduced gestational age at delivery (β: -2.3 weeks (95%: -3.4, -1.3)), as was the highest vs lowest cumulative dose trajectory group (β: -2.6 weeks (95%: -3.6, -1.5)). In pregnant women with rheumatoid arthritis, patterns of higher prednisone dose were associated with shorter gestational length compared with lower dose. Copyright © 2018 John Wiley & Sons, Ltd.

Time course of ozone-induced changes in breathing pattern in healthy exercising humans.

PubMed

Schelegle, Edward S; Walby, William F; Adams, William C

2007-02-01

We examined the time course of O3-induced changes in breathing pattern in 97 healthy human subjects (70 men and 27 women). One- to five-minute averages of breathing frequency (f(B)) and minute ventilation (Ve) were used to generate plots of cumulative breaths and cumulative exposure volume vs. time and cumulative exposure volume vs. cumulative breaths. Analysis revealed a three-phase response; delay, no response detected; onset, f(B) began to increase; response, f(B) stabilized. Regression analysis was used to identify four parameters: time to onset, number of breaths at onset, cumulative inhaled dose of ozone at onset of O3-induced tachypnea, and the percent change in f(B). The effect of altering O3 concentration, Ve, atropine treatment, and indomethacin treatment were examined. We found that the lower the O3 concentration, the greater the number of breaths at onset of tachypnea at a fixed ventilation, whereas number of breaths at onset of tachypnea remains unchanged when Ve is altered and O3 concentration is fixed. The cumulative inhaled dose of O3 at onset of tachypnea remained constant and showed no relationship with the magnitude of percent change in f(B). Atropine did not affect any of the derived parameters, whereas indomethacin did not affect time to onset, number of breaths at onset, or cumulative inhaled dose of O3 at onset of tachypnea but did attenuate percent change in f(B). The results are discussed in the context of dose response and intrinsic mechanisms of action.

A six month mitotane course induced sustained correction of hypercortisolism in a young woman with PPNAD and Carney complex.

PubMed

Cignarelli, M; Picca, G; Campo, M; Margaglione, M; Marino, A; Logoluso, F; Giorgino, F

2005-01-01

A low-dose mitotane (MT) regimen was evaluated as a pharmacological approach for correcting the severe hypercortisolism in a young woman affected by Carney complex (CNC) and primary pigmented nodular adrenocortical disease (PPNAD). In the first 12 week period, the MT daily dose was progressively increased from 0.5 to 4.0 g/day. This dosage was maintained for an additional 16 weeks (cumulative dose 602 g, plasma MT maximum level 12 microg/ml), and then stopped because of sustained signs of hypoadrenalism requiring prednisone replacement. Complete regression of seborrhea, acne, and plethora was observed after 8 weeks of treatment (cumulative dose 95 g). Regular menses returned after 13 weeks (cumulative dose 197 g, plasma MT 8 microg/ml). Profound decrease of both serum cortisol (from 615 to 220 nmol/l) and urinary free cortisol (UFC) values (from 1498 to 477 nmol/day) was noted after 16 weeks of treatment (cumulative dose 314 g, plasma MT 8 microg/ml). MT treatment was associated with mild gastric discomfort and reversible increase of cholesterol plasma levels. Low serum cortisol and UFC were still observed 41 weeks after MT was discontinued (plasma MT 0.2 microg/ml). Our report demonstrates that low dose MT treatment may be a safe and effective modality for a sustained correction of hypercortisolism by PPNAD in subjects with CNC waiting for surgery.

Temporal analysis of the October 1989 proton flare using computerized anatomical models

NASA Technical Reports Server (NTRS)

Simonsen, L. C.; Cucinotta, F. A.; Atwell, W.; Nealy, J. E.

1993-01-01

The GOES-7 time history data of hourly averaged integral proton fluxes at various particle kinetic energies are analyzed for the solar proton event that occurred between October 19 and 29, 1989. By analyzing the time history data, the dose rates which may vary over many orders of magnitude in the early phases of the flare can be estimated as well as the cumulative dose as a function of time. Basic transport calculations are coupled with detailed body organ thickness distributions from computerized anatomical models to estimate dose rates and cumulative doses to 20 critical body organs. For a 5-cm-thick water shield, cumulative skin, eye, and blood-forming-organ dose equivalents of 1.27, 1.23, and 0.41 Sv, respectively, are estimated. These results are approximately 40-50 percent less than the widely used 0- and 5-cm slab dose estimates. The risk of cancer incidence and mortality are also estimated for astronauts protected by various water shield thicknesses.

Pulmonary deposition modeling with airborne fiber exposure data: a study of workers manufacturing refractory ceramic fibers.

PubMed

Lentz, Thomas J; Rice, Carol H; Succop, Paul A; Lockey, James E; Dement, John M; LeMasters, Grace K

2003-04-01

Increasing production of refractory ceramic fiber (RCF), a synthetic vitreous material with industrial applications (e.g., kiln insulation), has created interest in potential respiratory effects of exposure to airborne fibers during manufacturing. An ongoing study of RCF manufacturing workers in the United States has indicated an association between cumulative fiber exposure and pleural plaques. Fiber sizing data, obtained from electron microscopy analyses of 118 air samples collected in three independent studies over a 20-year period (1976-1995), were used with a computer deposition model to estimate pulmonary dose of fibers of specified dimensions for 652 former and current RCF production workers. Separate dose correction factors reflecting differences in fiber dimensions in six uniform job title groups were used with data on airborne fiber concentration and employment duration to calculate cumulative dose estimates for each worker. From review of the literature, critical dimensions (diameter <0.4 microm, length <10 microm) were defined for fibers that may translocate to the parietal pleura. Each of three continuous exposure/dose metrics analyzed in separate logistic regression models was significantly related to plaques, even after adjusting for possible past asbestos exposure: cumulative fiber exposure, chi(2) = 15.2 (p < 0.01); cumulative pulmonary dose (all fibers), chi(2) = 14.6 (p < 0.01); cumulative pulmonary dose (critical dimension fibers), chi(2) = 12.4 (p < 0.01). Odds ratios (ORs) were calculated for levels of each metric. Increasing ORs were statistically significant for the two highest dose levels of critical dimension fibers (level three, OR = 11, 95%CI = [1.4, 98]; level four, OR = 25, 95%CI = [3.2, 190]). Similar associations existed for all metrics after adjustment for possible asbestos exposure. It was concluded that development of pleural plaques follows exposure- and dose-response patterns, and that airborne fibers in RCF manufacturing facilities include those with critical dimensions associated with pleural plaque formation. Analysis of additional air samples may improve estimates of the dose-response relationship.

Cumulative childhood trauma and psychological maladjustment of sexually abused children in Korea: mediating effects of emotion regulation.

PubMed

Choi, Ji Young; Oh, Kyung Ja

2014-02-01

The purpose of the present study was to identify the mediating effects of emotion regulation on the association between cumulative childhood trauma and behavior problems in sexually abused children in Korea, using structural equation modeling (SEM). Data were collected on 171 children (ages 6-13 years) referred to a public counseling center for sexual abuse in Seoul, Korea. Cumulative childhood traumas were defined on the basis of number of traumas (physical abuse, witnessing domestic violence, neglect, traumatic separation from parent, and sexual abuse) and the severity and duration of traumas. Children were evaluated by their parents on emotion regulation using the Emotion Regulation Checklist and internalizing and externalizing behavior problems using the Korean-Child Behavior Checklist. SEM analyses confirmed the complete mediation model, in which emotion dysregulation fully mediates the relationship between cumulative childhood traumas and internalizing/externalizing behavior problems. These findings indicate that emotion regulation is an important mechanism that can explain the negative effects of cumulative childhood traumas and that there is a need to focus on emotion regulation in sexually abused children exposed to cumulative trauma. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sex-related differential susceptibility to doxorubicin-induced cardiotoxicity in B6C3F{sub 1} mice

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

Jenkins, G. Ronald

Sex is a risk factor for development of cardiotoxicity, induced by the anti-cancer drug, doxorubicin (DOX), in humans. To explore potential mechanisms underlying differential susceptibility to DOX between sexes, 8-week old male and female B6C3F{sub 1} mice were dosed with 3 mg/kg body weight DOX or an equivalent volume of saline via tail vein once a week for 6, 7, 8, and 9 consecutive weeks, resulting in 18, 21, 24, and 27 mg/kg cumulative DOX doses, respectively. At necropsy, one week after each consecutive final dose, the extent of myocardial injury was greater in male mice compared to females asmore » indicated by higher plasma concentrations of cardiac troponin T at all cumulative DOX doses with statistically significant differences between sexes at the 21 and 24 mg/kg cumulative doses. A greater susceptibility to DOX in male mice was further confirmed by the presence of cytoplasmic vacuolization in cardiomyocytes, with left atrium being more vulnerable to DOX cardiotoxicity. The number of TUNEL-positive cardiomyocytes was mostly higher in DOX-treated male mice compared to female counterparts, showing a statistically significant sex-related difference only in left atrium at 21 mg/kg cumulative dose. DOX-treated male mice also had an increased number of γ-H2A.X-positive (measure of DNA double-strand breaks) cardiomyocytes compared to female counterparts with a significant sex effect in the ventricle at 27 mg/kg cumulative dose and right atrium at 21 and 27 mg/kg cumulative doses. This newly established mouse model provides a means to identify biomarkers and access potential mechanisms underlying sex-related differences in DOX-induced cardiotoxicity. - Highlights: • Doxorubicin caused greater heart injury in male mice than females. • Doxorubicin caused vacuolization in cardiomyocytes only in male mice. • TUNEL-positive cardiomyocytes was higher in DOX-treated male mice. • γ-H2A.X-positive cardiomyocytes was greater in DOX-treated male mice.« less

The association between cumulative adversity and mental health: considering dose and primary focus of adversity.

PubMed

Keinan, Giora; Shrira, Amit; Shmotkin, Dov

2012-09-01

The study addressed the dose-response model in the association of cumulative adversity with mental health. Data of 1,725 participants aged 50+ were drawn from the Israeli component of the Survey of Health, Ageing, and Retirement in Europe. Measures included an inventory of potentially traumatic events, distress (lifetime depression, depressive symptoms), and well-being (quality of life, optimism/hope). The maximal effect of cumulative trauma emerged in the contrast between 0-2 and 3+ events, where the higher number of events related to higher distress but also to higher well-being. While self-oriented adversity revealed no, or negative, association with well-being, other-oriented adversity revealed a positive association. The study suggests an experiential dose of cumulative adversity leading to a co-activation of distress and well-being. The source of this co-activation seems to be other-oriented adversity.

Cumulative or delayed nephrotoxicity after cisplatin (DDP) treatment.

PubMed

Pinnarò, P; Ruggeri, E M; Carlini, P; Giovannelli, M; Cognetti, F

1986-04-30

The present retrospective study reports data regarding renal toxicity in 115 patients (63 males, 52 females; median age, 56 years) who received cumulative doses of cisplatin (DDP) greater than or equal to 200 mg/m2. DDP was administered alone or in combination at a dose of 50-70 mg/m2 in 91 patients, and at a dose of 100 mg/m2 in 22 patients. Two patients after progression of ovarian carcinoma treated with conventional doses of DDP received 4 and 2 courses, respectively, of high-dose DDP (40 mg/m2 for 5 days) in hypertonic saline. The median number of DDP courses was 6 (range 2-14), and the median cumulative dose was 350 mg/m2 (range, 200-1200). Serum creatinine and urea nitrogen were determined before initiating the treatment and again 13-16 days after each administration. The incidence of azotemia (creatinina levels that exceeded 1.5 mg/dl) was similar before (7.8%) and after (6.1%) DDP doses of 200 mg/m2. Azotemia appears to be related to the association of DDP with other potentially nephrotoxic antineoplastic drugs (methotrexate) more than to the dose per course of DDP. Of 59 patients followed for 2 months or more after discontinuing the DDP treatment, 3 (5.1%) presented creatinine values higher than 1.5 mg/dl. The data deny that the incidence of nephrotoxicity is higher in patients receiving higher cumulative doses of DDP and confirm that increases in serum creatinine levels may occur some time after discontinuation of the drug.

Cumulative radiation exposure and cancer risk estimation in children with heart disease.

PubMed

Johnson, Jason N; Hornik, Christoph P; Li, Jennifer S; Benjamin, Daniel K; Yoshizumi, Terry T; Reiman, Robert E; Frush, Donald P; Hill, Kevin D

2014-07-08

Children with heart disease are frequently exposed to imaging examinations that use ionizing radiation. Although radiation exposure is potentially carcinogenic, there are limited data on cumulative exposure and the associated cancer risk. We evaluated the cumulative effective dose of radiation from all radiation examinations to estimate the lifetime attributable risk of cancer in children with heart disease. Children ≤6 years of age who had previously undergone 1 of 7 primary surgical procedures for heart disease at a single institution between 2005 and 2010 were eligible for the study. Exposure to radiation-producing examinations was tabulated, and cumulative effective dose was calculated in millisieverts. These data were used to estimate lifetime attributable risk of cancer above baseline using the approach of the Committee on Biological Effects of Ionizing Radiation VII. The cohort included 337 children exposed to 13 932 radiation examinations. Conventional radiographs represented 92% of examinations, whereas cardiac catheterization and computed tomography accounted for 81% of cumulative exposure. Overall median cumulative effective dose was 2.7 mSv (range, 0.1-76.9 mSv), and the associated lifetime attributable risk of cancer was 0.07% (range, 0.001%-6.5%). Median lifetime attributable risk of cancer ranged widely depending on surgical complexity (0.006%-1.6% for the 7 surgical cohorts) and was twice as high in females per unit exposure (0.04% versus 0.02% per 1-mSv effective dose for females versus males, respectively; P<0.001). Overall radiation exposures in children with heart disease are relatively low; however, select cohorts receive significant exposure. Cancer risk estimation highlights the need to limit radiation dose, particularly for high-exposure modalities. © 2014 American Heart Association, Inc.

The Use of Glyburide Compared With Other Sulfonylureas and the Risk of Cancer in Patients With Type 2 Diabetes.

PubMed

Tuccori, Marco; Wu, Jennifer W; Yin, Hui; Majdan, Agnieszka; Azoulay, Laurent

2015-11-01

To determine whether the use of glyburide is associated with an increased risk of cancer compared with the use of other second-generation sulfonylureas among patients with type 2 diabetes. The U.K. Clinical Practice Research Datalink was used to conduct a cohort study among 52,600 patients newly prescribed glyburide or other second-generation sulfonylureas between 1 January 1988 and 31 July 2013. A time-dependent Cox proportional hazards model was used to estimate adjusted hazard ratios (HRs) and 95% CIs of any cancer associated with the use of glyburide compared with the use of second-generation sulfonylureas. Secondary analyses were conducted to determine whether the association varied with cumulative duration of use and cumulative dose (expressed as defined daily dose [DDD]). During 280,288 person-years of follow-up, 4,105 patients were given a new diagnosis of cancer (incidence rate 14.6 per 1,000 person-years). Overall, when compared with the use of other second-generation sulfonylureas, the use of glyburide was associated with a nonsignificant increased risk of any cancer (HR 1.09 [95% CI 0.98-1.22]). In secondary analyses, duration- and dose-response relationships were observed, with longer cumulative durations and cumulative doses associated with an increased risk of any cancer (>36 months: HR 1.21 [95% CI: 1.03-1.42]; >1,096 DDDs: HR 1.27 [95% CI 1.06-1.51]). In this population-based cohort study, longer cumulative durations and higher cumulative doses of glyburide were associated with an increased risk of cancer. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Safety of {sup 90}Y Radioembolization in Patients Who Have Undergone Previous External Beam Radiation Therapy

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

Lam, Marnix G.E.H.; Department of Radiology and Nuclear Medicine, University Medical Center Utrecht; Abdelmaksoud, Mohamed H.K.

2013-10-01

Purpose: Previous external beam radiation therapy (EBRT) is theoretically contraindicated for yttrium-90 ({sup 90}Y) radioembolization (RE) because the liver has a lifetime tolerance to radiation before becoming vulnerable to radiation-induced liver disease. We analyzed the safety of RE as salvage treatment in patients who had previously undergone EBRT. Methods and Materials: Between June 2004 and December 2010, a total of 31 patients who had previously undergone EBRT were treated with RE. Three-dimensional treatment planning with dose–volume histogram (DVH) analysis of the liver was used to calculate the EBRT liver dose. Liver-related toxicities including RE-induced liver disease (REILD) were reviewed andmore » classified according to Common Terminology Criteria for Adverse Events version 4.02. Results: The mean EBRT and RE liver doses were 4.40 Gy (range, 0-23.13 Gy) and 57.9 Gy (range, 27.0-125.9 Gy), respectively. Patients who experienced hepatotoxicity (≥grade2; n=12) had higher EBRT mean liver doses (7.96 ± 8.55 Gy vs 1.62 ± 3.39 Gy; P=.037), the only independent predictor in multivariate analysis. DVH analysis showed that the fraction of liver exposed to ≥30 Gy (V30) was the strongest predictor of hepatotoxicity (10.14% ± 12.75% vs 0.84% ± 3.24%; P=.006). All patients with V30 >13% experienced hepatotoxicity. Fatal REILD (n=2) occurred at the 2 highest EBRT mean liver doses (20.9 Gy and 23.1 Gy) but also at the highest cumulative liver doses (91.8 Gy and 149 Gy). Conclusions: Prior exposure of the liver to EBRT may lead to increased liver toxicity after RE treatment, depending on fractional liver exposure and dose level. The V30 was the strongest predictor of toxicity. RE appears to be safe for the treatment of hepatic malignancies only in patients who have had limited hepatic exposure to prior EBRT.« less

Benchmark Dose Analysis from Multiple Datasets: The Cumulative Risk Assessment for the N-Methyl Carbamate Pesticides

EPA Science Inventory

The US EPA’s N-Methyl Carbamate (NMC) Cumulative Risk assessment was based on the effect on acetylcholine esterase (AChE) activity of exposure to 10 NMC pesticides through dietary, drinking water, and residential exposures, assuming the effects of joint exposure to NMCs is dose-...

Age-Based Methods to Explore Time-Related Variables in Occupational Epidemiology Studies

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

Janice P. Watkins, Edward L. Frome, Donna L. Cragle

2005-08-31

Although age is recognized as the strongest predictor of mortality in chronic disease epidemiology, a calendar-based approach is often employed when evaluating time-related variables. An age-based analysis file, created by determining the value of each time-dependent variable for each age that a cohort member is followed, provides a clear definition of age at exposure and allows development of diverse analytic models. To demonstrate methods, the relationship between cancer mortality and external radiation was analyzed with Poisson regression for 14,095 Oak Ridge National Laboratory workers. Based on previous analysis of this cohort, a model with ten-year lagged cumulative radiation doses partitionedmore » by receipt before (dose-young) or after (dose-old) age 45 was examined. Dose-response estimates were similar to calendar-year-based results with elevated risk for dose-old, but not when film badge readings were weekly before 1957. Complementary results showed increasing risk with older hire ages and earlier birth cohorts, since workers hired after age 45 were born before 1915, and dose-young and dose-old were distributed differently by birth cohorts. Risks were generally higher for smokingrelated than non-smoking-related cancers. It was difficult to single out specific variables associated with elevated cancer mortality because of: (1) birth cohort differences in hire age and mortality experience completeness, and (2) time-period differences in working conditions, dose potential, and exposure assessment. This research demonstrated the utility and versatility of the age-based approach.« less

Chromosome aberrations in workers occupationally exposed to tritium.

PubMed

Tawn, E Janet; Curwen, Gillian B; Riddell, Anthony E

2018-06-01

This paper reports the findings of an historical chromosome analysis for unstable aberrations, undertaken on 34 nuclear workers with monitored exposure to tritium. The mean recorded β-particle dose from tritium was 9.33 mGy (range 0.25-79.71 mGy) and the mean occupational dose from external, mainly γ-ray, irradiation was 1.94 mGy (range 0.00-7.71 mGy). The dicentric frequency of 1.91 ± 0.53 × 10 -3 per cell was significantly raised, in comparison with that of 0.61 ± 0.30 × 10 -3 per cell for a group of 66 comparable worker controls unexposed to occupational radiation. The frequency of total aberrations was also significantly higher in the tritium workers. Comparisons with in vitro studies indicate that at these dose levels an increase in aberration frequency is not expected. However, the available historical tritium dose records were produced for the purposes of radiological protection and based on a methodology that has since been updated, so tritium doses are subject to considerable uncertainty. It is therefore recommended that, if possible, tritium doses are reassessed using information on historical recording practices in combination with current dosimetry methodology, and that further chromosome studies are undertaken using modern FISH techniques to establish stable aberration frequencies, as these will provide information on a cumulative biological effect.

Safety and efficacy of fixed-dose 10 mg daily isotretinoin treatment for acne vulgaris in Malaysia.

PubMed

Yap, Felix Boon-Bin

2017-09-01

Low-dose isotretinoin is used to reduce side effects albeit higher relapse. This study aimed to determine the efficacy and safety of fixed-dose 10 mg daily isotretinoin for the treatment of acne. This prospective study was performed between 2011 and 2015. All 150 patients were given 10 mg daily isotretinoin until a cumulative dose of 90-110 mg/kg. The mean age was 26.6 years with 64.7% moderate acne, 29.3% severe, and 6% very severe. The mean cumulative dose was 98.8 ± 6.05 mg/kg. All 150 patients had total clearance with a mean time to clearance of 24.0 weeks. Patients with severe/very severe acne had higher cumulative dosage (102.1 vs. 97.0, P < 0.001) and longer duration to clearance (32.9 weeks vs. 19.1 weeks, P < 0.001). Mild relapse was seen in 4%. The mean time to relapse was 32.3 weeks. Lip dryness was the commonest side effects (100%). Mild transient elevation of liver enzymes was detected in 3.3% and a slight increase of serum lipid in 2.7% with no treatment discontinuation. Fixed-dose 10 mg daily treatment with isotretinoin until a cumulative dose of 90-110 mg/kg is safe with low relapse rate. © 2016 Wiley Periodicals, Inc.

Background Ionizing Radiation and the Risk of Childhood Cancer: A Census-Based Nationwide Cohort Study

PubMed Central

Lupatsch, Judith E.; Zwahlen, Marcel; Röösli, Martin; Niggli, Felix; Grotzer, Michael A.; Rischewski, Johannes; Egger, Matthias; Kuehni, Claudia E.

2015-01-01

Background Exposure to medium or high doses of ionizing radiation is a known risk factor for cancer in children. The extent to which low-dose radiation from natural sources contributes to the risk of childhood cancer remains unclear. Objectives In a nationwide census-based cohort study, we investigated whether the incidence of childhood cancer was associated with background radiation from terrestrial gamma and cosmic rays. Methods Children < 16 years of age in the Swiss National Censuses in 1990 and 2000 were included. The follow-up period lasted until 2008, and incident cancer cases were identified from the Swiss Childhood Cancer Registry. A radiation model was used to predict dose rates from terrestrial and cosmic radiation at locations of residence. Cox regression models were used to assess associations between cancer risk and dose rates and cumulative dose since birth. Results Among 2,093,660 children included at census, 1,782 incident cases of cancer were identified including 530 with leukemia, 328 with lymphoma, and 423 with a tumor of the central nervous system (CNS). Hazard ratios for each millisievert increase in cumulative dose of external radiation were 1.03 (95% CI: 1.01, 1.05) for any cancer, 1.04 (95% CI: 1.00, 1.08) for leukemia, 1.01 (95% CI: 0.96, 1.05) for lymphoma, and 1.04 (95% CI: 1.00, 1.08) for CNS tumors. Adjustment for a range of potential confounders had little effect on the results. Conclusions Our study suggests that background radiation may contribute to the risk of cancer in children, including leukemia and CNS tumors. Citation Spycher BD, Lupatsch JE, Zwahlen M, Röösli M, Niggli F, Grotzer MA, Rischewski J, Egger M, Kuehni CE, for the Swiss Pediatric Oncology Group and the Swiss National Cohort. 2015. Background ionizing radiation and the risk of childhood cancer: a census-based nationwide cohort study. Environ Health Perspect 123:622–628; http://dx.doi.org/10.1289/ehp.1408548 PMID:25707026

Gamma irradiator dose mapping simulation using the MCNP code and benchmarking with dosimetry.

PubMed

Sohrabpour, M; Hassanzadeh, M; Shahriari, M; Sharifzadeh, M

2002-10-01

The Monte Carlo transport code, MCNP, has been applied in simulating dose rate distribution in the IR-136 gamma irradiator system. Isodose curves, cumulative dose values, and system design data such as throughputs, over-dose-ratios, and efficiencies have been simulated as functions of product density. Simulated isodose curves, and cumulative dose values were compared with dosimetry values obtained using polymethyle-methacrylate, Fricke, ethanol-chlorobenzene, and potassium dichromate dosimeters. The produced system design data were also found to agree quite favorably with those of the system manufacturer's data. MCNP has thus been found to be an effective transport code for handling of various dose mapping excercises for gamma irradiators.

High- and low-dose-rate intraoperative radiotherapy for thoracic malignancies resected with close or positive margins.

PubMed

Fleming, Christopher; Rimner, Andreas; Cohen, Gil'ad N; Woo, Kaitlin M; Zhang, Zhigang; Rosenzweig, Kenneth E; Alektiar, Kaled M; Zelefsky, Michael J; Bains, Manjit S; Wu, Abraham J

2016-01-01

Local recurrence is a significant problem after surgical resection of thoracic tumors. As intraoperative radiotherapy (IORT) can deliver radiation directly to the threatened margin, we have used this therapy in an attempt to reduce local recurrence, using high-dose-rate (HDR) as well as low-dose-rate (LDR) techniques. We performed a retrospective review of patients undergoing LDR ((125)I) mesh placement or HDR ((192)Ir) afterloading therapy during lung tumor resection between 2001 and 2013 at our institution. Competing risks methods were used to estimate the cumulative incidence of local failure. We also assessed possible predictive factors of local failure. Fifty-nine procedures (41 LDR and 18 HDR) were performed on 58 patients. Median follow-up was 55.1 months. Cumulative incidence of local failure at 1, 2, and 3 years was 28.5%, 34.2%, and 34.2%, respectively. Median overall survival was 39.9 months. There was no significant difference in local failure according to margin status, HDR vs. LDR, use of adjuvant external beam radiotherapy, or metastatic vs. primary tumor. Two patients (3.4%) experienced Grade 3+ toxicities likely related to brachytherapy. Additionally, 7 patients experienced Grade 3+ postsurgical complications unlikely related to brachytherapy. IORT is associated with good local control after resection of thoracic tumors otherwise at very high risk for local recurrence. There is a low incidence of severe toxicity attributable to brachytherapy. HDR-IORT appears to have equivalent outcomes to LDR-IORT. HDR or LDR-IORT can, therefore, be considered in situations where the oncologic completeness of thoracic tumor resection is in doubt. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Impact of gender on efficacy and acute toxicity of alkylating agent -based chemotherapy in Ewing sarcoma: secondary analysis of the Euro-Ewing99-R1 trial.

PubMed

van den Berg, Henk; Paulussen, Michael; Le Teuff, Gwénaël; Judson, Ian; Gelderblom, Hans; Dirksen, Uta; Brennan, Bernadette; Whelan, Jeremy; Ladenstein, Ruth Lydia; Marec-Berard, Perrine; Kruseova, Jarmila; Hjorth, Lars; Kühne, Thomas; Brichard, Benedicte; Wheatley, Keith; Craft, Alan; Juergens, Heribert; Gaspar, Nathalie; Le Deley, Marie-Cécile

2015-11-01

Based on the randomised Euro-EWING99-R1 trial, vincristine, adriamycin, cyclophosphamide (VAC) may be able to replace vincristine, adriamycin, ifosfamide (VAI) in the treatment of standard-risk Ewing sarcoma. However some heterogeneity of treatment effect by gender was observed. The current exploratory study aimed at investigating the influence of gender on treatment efficacy and acute toxicity. Impact of gender on event-free survival (EFS), acute toxicity by course, switches between treatment arms and cumulative dose of alkylating agents was evaluated in multivariable models adjusted for age including terms to test for heterogeneity of treatment effect by gender. The analysis of the EFS was performed on the intention-to-treat population. EFS did not significantly differ between the 509 males and 347 females (p=0.33), but an interaction in terms of efficacy was suspected between treatment and gender (p=0.058): VAC was associated with poorer EFS than VAI in males, hazard ratio (HR) (VAC/VAI)=1.37 [95% confidence interval (CI), 0.98-1.90], contrasting with HR=0.81 [95%CI, 0.53-1.24] in females. Severe toxicity was more frequent in females, whatever the toxicity type. Thirty patients switched from VAI to VAC (9/251 males, 4%, and 21/174 females, 12%) mostly due to renal toxicity, and three from VAC to VAI (2/258 males, 0.8%, and 1/173 females, 0.6%). A reduction of alkylating agent cumulative dose >20% was more frequent in females (15% versus 9%, p=0.005), with no major difference between VAC and VAI (10% versus 13%, p=0.15). Differences of acute toxicity rate and cumulative doses of alkylating agents could not explain the marginal interaction observed in the Euro-EWING99-R1 trial data. Effects of gender-dependent polymorphism/activity of metabolic enzymes (e.g. known for CYP2B6) of ifosfamide versus cyclophosphamide should be explored. External data are required to further evaluate whether there is heterogeneity of alkylating agent effect by gender. NCT00987636 and EudraCT 2008-003658-13. Copyright © 2015 Elsevier Ltd. All rights reserved.

Salivary cortisol reactivity in preschoolers is associated with hair cortisol and behavioral problems.

PubMed

Kao, Katie; Doan, Stacey N; St John, Ashley M; Meyer, Jerrold S; Tarullo, Amanda R

2018-01-01

The interplay between children's cortisol reactivity to challenge and cumulative cortisol exposure is not well understood. Examining the role of cortisol reactivity in early childhood may elucidate biological mechanisms that contribute to children's chronic physiological stress and behavioral dysregulation. In a sample of 65 preschool-aged children, we examined the relation between children's salivary cortisol reactivity to challenging tasks and their hair cortisol concentration (HCC). While both are biomarkers of the hypothalamic-pituitary-adrenal (HPA) axis, salivary cortisol reactivity reflects an acute cortisol response to a stressor and HCC reflects cumulative cortisol exposure. In addition, we examined the relations of these stress biomarkers with internalizing and externalizing problems. Salivary cortisol reactivity was associated with higher HCC and with increased externalizing behaviors. Child HCC also was positively correlated with parent HCC. Results highlight the contributions of salivary cortisol reactivity to children's cumulative cortisol exposure, which may add to their biological risk for health problems later. The observed association between externalizing problems and salivary cortisol reactivity indicates concordances between dysregulated behavioral reactions and dysregulated cortisol responses to challenges. The finding that salivary cortisol reactivity to challenge in early childhood plays a role in children's cumulative cortisol exposure and behavioral development suggests pathways through which cortisol reactivity may influence long-term physical and mental health.

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

PubMed Central

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

2016-01-01

Aim To study the influence of prednisone dose during the first month after systemic lupus erythematosus (SLE) diagnosis (prednisone-1) on glucocorticoid burden during the subsequent 11 months (prednisone-2–12). Methods 223 patients from the Registro Español de Lupus Eritematoso Sistémico inception cohort were studied. The cumulative dose of prednisone-1 and prednisone-2–12 were calculated and recoded into a four-level categorical variable: no prednisone, low dose (up to 7.5 mg/day), medium dose (up to 30 mg/day) and high dose (over 30 mg/day). The association between the cumulative prednisone-1 and prednisone-2–12 doses was tested. We analysed whether the four-level prednisone-1 categorical variable was an independent predictor of an average dose >7.5 mg/day of prednisone-2–12. Adjusting variables included age, immunosuppressives, antimalarials, methyl-prednisolone pulses, lupus nephritis and baseline SLE Disease Activity Index (SLEDAI). Results Within the first month, 113 patients (51%) did not receive any prednisone, 24 patients (11%) received average low doses, 46 patients (21%) received medium doses and 40 patients (18%) received high doses. There was a strong association between prednisone-1 and prednisone-2–12 dose categories (p<0.001). The cumulative prednisone-1 dose was directly associated with the cumulative prednisone-2–12 dose (p<0.001). Compared with patients on no prednisone, patients taking medium (adjusted OR 5.27, 95% CI 2.18 to 12.73) or high-dose prednisone-1 (adjusted OR 10.5, 95% CI 3.8 to 29.17) were more likely to receive prednisone-2–12 doses of >7.5 mg/day, while patients receiving low-dose prednisone-1 were not (adjusted OR 1.4, 95% CI 0. 0.38 to 5.2). If the analysis was restricted to the 158 patients with a baseline SLEDAI of ≥6, the model did not change. Conclusion The dose of prednisone during the first month after the diagnosis of SLE is an independent predictor of prednisone burden during the following 11 months. PMID:27547439

Radon and leukemia in the Danish study: another source of dose.

PubMed

Harley, Naomi H; Robbins, Edith S

2009-10-01

An epidemiologic study of childhood leukemia in Denmark (2,400 cases; 6,697 controls) from 1968 to 1994 suggested a weak, but statistically significant, association of residential radon exposure and acute childhood lymphoblastic leukemia (ALL). The Danish study estimated a relative risk (RR) = 1.56 (95% CI, 1.05-2.30) for a cumulative exposure of 1,000 Bq m-3 y. For an exposure duration of 10 y their RR corresponds to a radon concentration of 100 Bq m-3. There are two dose pathways of interest where alpha particles could damage potential stem cells for ALL. One is the alpha dose to bone marrow, and two is the dose to bronchial mucosa where an abundance of circulating lymphocytes is found. Compared with an exposure of about 1 mSv y-1 from natural external background, radon and decay products contribute an additional 10 to 60% to the bone marrow equivalent dose. The other pathway for exposure of T (or B) lymphocytes is within the tracheobronchial epithelium (BE). Inhaled radon decay products deposit on the relatively small area of airway surfaces and deliver a significant dose to the nearby basal or mucous cells implicated in human lung cancer. Lymphocytes are co-located with basal cells and are half as abundant. Using a 10-y exposure to 100 Bq m-3, our dose estimates suggest that the equivalent dose to these lymphocytes could approach 1 Sv. The relatively high dose estimate to lymphocytes circulating through the BE, potential precursor cells for ALL, provides a dose pathway for an association.

Re-irradiation: outcome, cumulative dose and toxicity in patients retreated with stereotactic radiotherapy in the abdominal or pelvic region.

PubMed

Abusaris, Huda; Hoogeman, M; Nuyttens, Joost J

2012-12-01

The purpose of the present study was to explore the outcome, cumulative dose in tumor and organs at risk and toxicity after extra-cranial stereotactic re-irradiation. Twenty-seven patients were evaluated who had been re-irradiated with stereotactic body radiotherapy (SBRT) after conventional radiotherapy (CRT). The dose summation of the SBRT and CRT plans was done by dose point calculations accounting for fraction size by the linear-quadratic model. Efficacy and toxicity was scored by looking at the reduction in tumor size, pain and bleeding. Symptomatic response was observed in 96% of the patients. The median maximum SBRT dose to the tumor was 90 Gy(3) (range: 42-420 Gy(3)). The median cumulative dose for the rectum, bowel and bladder resulted in 104 Gy(3), 98 Gy(3) and 113 Gy(3), respectively. No grades 5, 4 and 3 acute and late toxicity was observed. re-irradiation to the same region using extra-cranial stereotactic radiotherapy is feasible and resulted in a 96% symptomatic response with low toxicity.

Intrathecal morphine for analgesia in children undergoing selective dorsal rhizotomy.

PubMed

Dews, T E; Schubert, A; Fried, A; Ebrahim, Z; Oswalt, K; Paranandi, L

1996-03-01

Selective dorsal root rhizotomy is performed for relief of spasticity in children with cerebral palsy. Postoperative pain relief can be provided by intrathecal morphine administered at the time of the procedure. We sought to define an optimal dose of intrathecal morphine in children undergoing selective rhizotomy, through a randomized, double-blinded prospective trial. After institutional approval and parental written informed consent, 27 patients, ages 3-10 years, were randomized to receive 10, 20, or 30 micrograms.kg-1 (Groups A, B, and C, respectively) of preservative-free morphine administered intrathecally by the surgeon after dural closure. Postoperatively, vital signs, pulse oximetry, and pain intensity scores were recorded hourly for 24 hr. Supplemental intravenous morphine was administered postoperatively according to a predetermined schedule based on pain scores. There was considerable individual variability in the time to initial morphine dosing and cumulative supplemental morphine dose. Time to first supplemental morphine dose was not different between groups. When compared to Groups A and B, cumulative 6-hr supplemental morphine dose was significantly lower in Group C (38.6 +/- 47 micrograms versus 79.1 +/- 74 and 189.6 +/- 126 for Groups A and B, respectively). By 12 hr, cumulative supplemental morphine dose was similar in Groups A and C. Group B consistently had a higher supplemental dose requirement than Groups A and C at 6, 12, and 18 hr. By 24 hr, there was no difference in cumulative dose among groups. Postoperative pain scores and the incidence of respiratory events, nausea, vomiting and pruritus were comparable among groups. These data suggest that intrathecal morphine at 30 micrograms.kg-1 provides the most intense analgesia at 6 hr following selective dorsal root rhizotomy, but was otherwise comparable to the 10 micrograms.kg-1 dose.

Cumulative effective dose and cancer risk for pediatric population in repetitive full spine follow-up imaging: How micro dose is the EOS microdose protocol?

PubMed

Law, Martin; Ma, Wang-Kei; Lau, Damian; Cheung, Kenneth; Ip, Janice; Yip, Lawrance; Lam, Wendy

2018-04-01

To evaluate and to obtain analytic formulation for the calculation of the effective dose and associated cancer risk using the EOS microdose protocol for scoliotic pediatric patients undergoing full spine imaging at different age of exposure; to demonstrate the microdose protocol capable of delivering lesser radiation dose and hence of further reducing cancer risk induction when compared with the EOS low dose protocol; to obtain cumulative effective dose and cancer risk for both genders scoliotic pediatrics of US and Hong Kong population using the microdose protocol. Organ absorbed doses of full spine exposed scoliotic pediatric patients have been simulated with the use of EOS microdose protocol imaging parameters input to the Monte Carlo software PCXMC. Gender and age specific effective dose has been calculated with the simulated organ absorbed dose using the ICRP-103 approach. The associated radiation induced cancer risk, expressed as lifetime attributable risk (LAR), has been estimated according to the method introduced in the Biological Effects of Ionizing Radiation VII report. Values of LAR have been estimated for scoliotic patients exposed repetitively during their follow up period at different age for US and Hong Kong population. The effective doses of full spine imaging with simultaneous posteroanterior and lateral projection for patients exposed at the age between 5 and 18 years using the EOS microdose protocol have been calculated within the range of 2.54-14.75 μSv. The corresponding LAR for US and Hong Kong population was ranged between 0.04 × 10 -6 and 0.84 × 10 -6 . Cumulative effective dose and cancer risk during follow-up period can be estimated using the results and are of information to patients and their parents. With the use of computer simulation and analytic formulation, we obtained the cumulative effective dose and cancer risk at any age of exposure for pediatric patients of US and Hong Kong population undergoing repetitive microdose protocol full spine imaging. Girls would be at a statistically significant higher cumulative cancer risk than boys undergoing the same microdose full spine imaging protocol and the same follow-up schedule. Copyright © 2018 Elsevier B.V. All rights reserved.

Bone fractures following external beam radiotherapy and limb-preservation surgery for lower extremity soft tissue sarcoma: relationship to irradiated bone length, volume, tumor location and dose.

PubMed

Dickie, Colleen I; Parent, Amy L; Griffin, Anthony M; Fung, Sharon; Chung, Peter W M; Catton, Charles N; Ferguson, Peter C; Wunder, Jay S; Bell, Robert S; Sharpe, Michael B; O'Sullivan, Brian

2009-11-15

To examine the relationship between tumor location, bone dose, and irradiated bone length on the development of radiation-induced fractures for lower extremity soft tissue sarcoma (LE-STS) patients treated with limb-sparing surgery and radiotherapy (RT). Of 691 LE-STS patients treated from 1989 to 2005, 31 patients developed radiation-induced fractures. Analysis was limited to 21 fracture patients (24 fractures) who were matched based on tumor size and location, age, beam arrangement, and mean total cumulative RT dose to a random sample of 53 nonfracture patients and compared for fracture risk factors. Mean dose to bone, RT field size (FS), maximum dose to a 2-cc volume of bone, and volume of bone irradiated to >or=40 Gy (V40) were compared. Fracture site dose was determined by comparing radiographic images and surgical reports to fracture location on the dose distribution. For fracture patients, mean dose to bone was 45 +/- 8 Gy (mean dose at fracture site 59 +/- 7 Gy), mean FS was 37 +/- 8 cm, maximum dose was 64 +/- 7 Gy, and V40 was 76 +/- 17%, compared with 37 +/- 11 Gy, 32 +/- 9 cm, 59 +/- 8 Gy, and 64 +/- 22% for nonfracture patients. Differences in mean, maximum dose, and V40 were statistically significant (p = 0.01, p = 0.02, p = 0.01). Leg fractures were more common above the knee joint. The risk of radiation-induced fracture appears to be reduced if V40 <64%. Fracture incidence was lower when the mean dose to bone was <37 Gy or maximum dose anywhere along the length of bone was <59 Gy. There was a trend toward lower mean FS for nonfracture patients.

Cancer mortality and occupational exposure to aromatic amines and inhalable aerosols in rubber tire manufacturing in Poland.

PubMed

de Vocht, Frank; Sobala, Wojciech; Wilczynska, Urszula; Kromhout, Hans; Szeszenia-Dabrowska, Neonila; Peplonska, Beata

2009-08-01

Most data on carcinogenic risk in the rubber industry are based on data from Western countries. This study assessed cancer risks in a retrospective cohort in a Polish tire manufacturing plant, relying on quantified exposure to inhalable aerosols and aromatic amines instead of job titles or external comparisons. Cumulative exposure for all exposures was assigned to cohort members based on estimates from a company-specific JEM. Cancer risks associated with cumulative exposure adjusted for co-exposures, gender and year of birth were calculated. Exposure levels were higher for women than for men. Aromatic amine exposure was significantly associated with increased urinary bladder cancer risk (RR=7.32-8.27), depending on exposure level, and prostate cancer at low levels only (RR=5.86). In women, increased risks were found for all cancers (RR=2.50) and of the digestive organs and peritoneum (RR=4.54) at low level only, while an exposure-response association with breast cancer risk was found. Inhalable aerosol exposure was associated with cancers of the liver and intrahepatic bile ducts in a dose-dependent manner, while dose-dependent reduced risks were found for respiratory cancers (most notably the larynx) and cancer of the colon. Increased risks for specific cancer sites in this rubber plant were similar to Western Europe and the US. However, several cancer risks were gender-specific which could relate to higher exposure levels in women or to differences in exposures to chemicals not assessed in this study.

Ionizing radiation exposure as a result of diagnostic imaging in patients with lymphoma.

PubMed

Crowley, M P; O'Neill, S B; Kevane, B; O'Neill, D C; Eustace, J A; Cahill, M R; Bird, B; Maher, M M; O'Regan, K; O'Shea, D

2016-05-01

Survival rates among patients with lymphoma continue to improve. Strategies aimed at reducing potential treatment-related toxicity are increasingly prioritized. While radiological procedures play an important role, ionizing radiation exposure has been linked to an increased risk of malignancy, particularly among individuals whose cumulative radiation exposure exceeds a specific threshold (75 millisieverts). Within this retrospective study, the cumulative radiation exposure dose was quantified for 486 consecutive patients with lymphoma. The median estimated total cumulative effective dose (CED) of ionizing radiation per subject was 69 mSv (42-118). However, younger patients (under 40 years) had a median CED of 89 mSv (55-124). This study highlights the considerable radiation exposure occurring among patients with lymphoma as a result of diagnostic imaging. To limit the risk of secondary carcinogenesis, consideration should be given to monitoring cumulative radiation exposure in individual patients as well as considering imaging modalities, which do not impart an ionizing radiation dose.

Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials.

PubMed

von Minckwitz, Gunter; Untch, Michael; Nüesch, Eveline; Loibl, Sibylle; Kaufmann, Manfred; Kümmel, Sherko; Fasching, Peter A; Eiermann, Wolfgang; Blohmer, Jens-Uwe; Costa, Serban Dan; Mehta, Keyur; Hilfrich, Jörn; Jackisch, Christian; Gerber, Bernd; du Bois, Andreas; Huober, Jens; Hanusch, Claus; Konecny, Gottfried; Fett, Werner; Stickeler, Elmar; Harbeck, Nadia; Müller, Volkmar; Jüni, Peter

2011-01-01

Pathological complete response (pCR) to neoadjuvant treatment correlates with outcome in breast cancer. We determined whether characteristics of neoadjuvant therapy are associated with pCR. We used multi-level models, which accounted for heterogeneity in pCR across trials and trial arms, to analyze individual patient data from 3332 women included in 7 German neoadjuvant trials with uniform protocols. PCR was associated with an increase in number of chemotherapy cycles (odds ratio [OR] 1.2 for every two additional cycles; P = 0.009), with higher cumulative anthracycline doses (OR 1.6; P = 0.002), higher cumulative taxane doses (OR 1.6; P = 0.009), and with capecitabine containing regimens (OR 1.62; P = 0.022). Association of pCR with increase in number of cycles appeared more pronounced in hormone receptor (HR)-positive tumors (OR 1.35) than in HR-negative tumors (OR 1.04; P for interaction = 0.046). Effect of anthracycline dose was particularly pronounced in HER2-negative tumors (OR 1.61), compared to HER2-positive tumors (OR 0.83; P for interaction = 0.14). Simultaneous trastuzumab treatment in HER2-positive tumors increased odds of pCR 3.2-fold (P < 0.001). No association of pCR and number of trastuzumab cycles was found (OR 1.20, P = 0.39). Dosing characteristics appear important for successful treatment of breast cancer. Longer treatment, higher cumulative doses of anthracyclines and taxanes, and the addition of capecitabine and trastuzumab are associated with better response. Tailoring according to breast cancer phenotype might be possible: longer treatment in HR-positive tumors, higher cumulative anthracycline doses for HER2-negative tumors, shorter treatment at higher cumulative doses for triple-negative tumors, and limited number of preoperative trastuzumab cycles in HER2-positive tumors.

10 CFR 835.203 - Combining internal and external equivalent doses.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Combining internal and external equivalent doses. 835.203 Section 835.203 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and External Exposure § 835.203 Combining internal and external equivalent doses. (a) The total effective dose...

Methods for Probabilistic Radiological Dose Assessment at a High-Level Radioactive Waste Repository.

NASA Astrophysics Data System (ADS)

Maheras, Steven James

Methods were developed to assess and evaluate the uncertainty in offsite and onsite radiological dose at a high-level radioactive waste repository to show reasonable assurance that compliance with applicable regulatory requirements will be achieved. Uncertainty in offsite dose was assessed by employing a stochastic precode in conjunction with Monte Carlo simulation using an offsite radiological dose assessment code. Uncertainty in onsite dose was assessed by employing a discrete-event simulation model of repository operations in conjunction with an occupational radiological dose assessment model. Complementary cumulative distribution functions of offsite and onsite dose were used to illustrate reasonable assurance. Offsite dose analyses were performed for iodine -129, cesium-137, strontium-90, and plutonium-239. Complementary cumulative distribution functions of offsite dose were constructed; offsite dose was lognormally distributed with a two order of magnitude range. However, plutonium-239 results were not lognormally distributed and exhibited less than one order of magnitude range. Onsite dose analyses were performed for the preliminary inspection, receiving and handling, and the underground areas of the repository. Complementary cumulative distribution functions of onsite dose were constructed and exhibited less than one order of magnitude range. A preliminary sensitivity analysis of the receiving and handling areas was conducted using a regression metamodel. Sensitivity coefficients and partial correlation coefficients were used as measures of sensitivity. Model output was most sensitive to parameters related to cask handling operations. Model output showed little sensitivity to parameters related to cask inspections.

Subcutaneous ofatumumab in patients with relapsing-remitting multiple sclerosis: The MIRROR study.

PubMed

Bar-Or, Amit; Grove, Richard A; Austin, Daren J; Tolson, Jerry M; VanMeter, Susan A; Lewis, Eric W; Derosier, Frederick J; Lopez, Monica C; Kavanagh, Sarah T; Miller, Aaron E; Sorensen, Per S

2018-05-15

To assess dose-response effects of the anti-CD20 monoclonal antibody ofatumumab on efficacy and safety outcomes in a phase 2b double-blind study of relapsing forms of multiple sclerosis (RMS). Patients (n = 232) were randomized to ofatumumab 3, 30, or 60 mg every 12 weeks, ofatumumab 60 mg every 4 weeks, or placebo for a 24-week treatment period, with a primary endpoint of cumulative number of new gadolinium-enhancing lesions (per brain MRI) at week 12. Relapses and safety/tolerability were assessed, and CD19+ peripheral blood B-lymphocyte counts measured. Safety monitoring continued weeks 24 to 48 with subsequent individualized follow-up evaluating B-cell repletion. The cumulative number of new lesions was reduced by 65% for all ofatumumab dose groups vs placebo ( p < 0.001). Post hoc analysis (excluding weeks 1-4) estimated a ≥90% lesion reduction vs placebo (week 12) for all cumulative ofatumumab doses ≥30 mg/12 wk. Dose-dependent CD19 B-cell depletion was observed. Notably, complete depletion was not necessary for a robust treatment effect. The most common adverse event was injection-related reactions (52% ofatumumab, 15% placebo), mild to moderate severity in 97%, most commonly associated with the first dose and diminishing on subsequent dosing. Imaging showed that all subcutaneous ofatumumab doses demonstrated efficacy (most robust: cumulative doses ≥30 mg/12 wk), with a safety profile consistent with existing ofatumumab data. This treatment effect also occurred with dosage regimens that only partially depleted circulating B cells. This study provides Class I evidence that for patients with RMS, ofatumumab decreases the number of new MRI gadolinium-enhancing lesions 12 weeks after treatment initiation. © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Subcutaneous ofatumumab in patients with relapsing-remitting multiple sclerosis

PubMed Central

Grove, Richard A.; Austin, Daren J.; Tolson, Jerry M.; VanMeter, Susan A.; Lewis, Eric W.; Derosier, Frederick J.; Lopez, Monica C.; Kavanagh, Sarah T.; Miller, Aaron E.; Sorensen, Per S.

2018-01-01

Objective To assess dose-response effects of the anti-CD20 monoclonal antibody ofatumumab on efficacy and safety outcomes in a phase 2b double-blind study of relapsing forms of multiple sclerosis (RMS). Methods Patients (n = 232) were randomized to ofatumumab 3, 30, or 60 mg every 12 weeks, ofatumumab 60 mg every 4 weeks, or placebo for a 24-week treatment period, with a primary endpoint of cumulative number of new gadolinium-enhancing lesions (per brain MRI) at week 12. Relapses and safety/tolerability were assessed, and CD19+ peripheral blood B-lymphocyte counts measured. Safety monitoring continued weeks 24 to 48 with subsequent individualized follow-up evaluating B-cell repletion. Results The cumulative number of new lesions was reduced by 65% for all ofatumumab dose groups vs placebo (p < 0.001). Post hoc analysis (excluding weeks 1–4) estimated a ≥90% lesion reduction vs placebo (week 12) for all cumulative ofatumumab doses ≥30 mg/12 wk. Dose-dependent CD19 B-cell depletion was observed. Notably, complete depletion was not necessary for a robust treatment effect. The most common adverse event was injection-related reactions (52% ofatumumab, 15% placebo), mild to moderate severity in 97%, most commonly associated with the first dose and diminishing on subsequent dosing. Conclusion Imaging showed that all subcutaneous ofatumumab doses demonstrated efficacy (most robust: cumulative doses ≥30 mg/12 wk), with a safety profile consistent with existing ofatumumab data. This treatment effect also occurred with dosage regimens that only partially depleted circulating B cells. Classification of evidence This study provides Class I evidence that for patients with RMS, ofatumumab decreases the number of new MRI gadolinium-enhancing lesions 12 weeks after treatment initiation. PMID:29695594

Infant attachment disorganization and moderation pathways to level and change in externalizing behavior during preschool ages.

PubMed

Wang, Feihong; Willoughby, Michael; Mills-Koonce, Roger; Cox, Martha J

2016-12-01

This research examined the child, parent, and family conditions under which attachment disorganization was related to both level and change in externalizing behavior during preschool among a community sample. Using the ordinary least squares regression, we found that attachment disorganization at 12 months significantly predicted children's externalizing behavior at 36 months and this prediction was not contingent on any other factors tested. For predicting changes in externalizing behavior from 36 to 60 months, we found a significant main effect of family cumulative risk and an interaction effect between attachment disorganization at 12 months and maternal sensitivity at 24 months. Specifically, high disorganization was related to a significant decrease in externalizing behavior from 36 to 60 months when maternal sensitivity at 24 months was high. Our main-effect findings replicated the significant effect of attachment disorganization and cumulative risk on externalizing behavior with preschool-aged children. Our interaction finding provided support for understanding the parenting conditions under which infant attachment disorganization may be related to change in externalizing behavior during preschool ages. Implications of the findings were discussed.

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials

PubMed Central

Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L.; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

2016-01-01

Purpose The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. Patients and Methods We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. Results A total of 13,008 toxicities were captured: 46% of patients’ first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m2, the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. Conclusions When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. PMID:26926682

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials.

PubMed

Lee, Shing M; Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

2016-04-20

The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. A total of 13,008 toxicities were captured: 46% of patients' first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m(2), the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. © 2016 by American Society of Clinical Oncology.

Measuring uncertainty in dose delivered to the cochlea due to setup error during external beam treatment of patients with cancer of the head and neck.

PubMed

Yan, M; Lovelock, D; Hunt, M; Mechalakos, J; Hu, Y; Pham, H; Jackson, A

2013-12-01

To use Cone Beam CT scans obtained just prior to treatments of head and neck cancer patients to measure the setup error and cumulative dose uncertainty of the cochlea. Data from 10 head and neck patients with 10 planning CTs and 52 Cone Beam CTs taken at time of treatment were used in this study. Patients were treated with conventional fractionation using an IMRT dose painting technique, most with 33 fractions. Weekly radiographic imaging was used to correct the patient setup. The authors used rigid registration of the planning CT and Cone Beam CT scans to find the translational and rotational setup errors, and the spatial setup errors of the cochlea. The planning CT was rotated and translated such that the cochlea positions match those seen in the cone beam scans, cochlea doses were recalculated and fractional doses accumulated. Uncertainties in the positions and cumulative doses of the cochlea were calculated with and without setup adjustments from radiographic imaging. The mean setup error of the cochlea was 0.04 ± 0.33 or 0.06 ± 0.43 cm for RL, 0.09 ± 0.27 or 0.07 ± 0.48 cm for AP, and 0.00 ± 0.21 or -0.24 ± 0.45 cm for SI with and without radiographic imaging, respectively. Setup with radiographic imaging reduced the standard deviation of the setup error by roughly 1-2 mm. The uncertainty of the cochlea dose depends on the treatment plan and the relative positions of the cochlea and target volumes. Combining results for the left and right cochlea, the authors found the accumulated uncertainty of the cochlea dose per fraction was 4.82 (0.39-16.8) cGy, or 10.1 (0.8-32.4) cGy, with and without radiographic imaging, respectively; the percentage uncertainties relative to the planned doses were 4.32% (0.28%-9.06%) and 10.2% (0.7%-63.6%), respectively. Patient setup error introduces uncertainty in the position of the cochlea during radiation treatment. With the assistance of radiographic imaging during setup, the standard deviation of setup error reduced by 31%, 42%, and 54% in RL, AP, and SI direction, respectively, and consequently, the uncertainty of the mean dose to cochlea reduced more than 50%. The authors estimate that the effects of these uncertainties on the probability of hearing loss for an individual patient could be as large as 10%.

Measuring uncertainty in dose delivered to the cochlea due to setup error during external beam treatment of patients with cancer of the head and neck

PubMed Central

Yan, M.; Lovelock, D.; Hunt, M.; Mechalakos, J.; Hu, Y.; Pham, H.; Jackson, A.

2013-01-01

Purpose: To use Cone Beam CT scans obtained just prior to treatments of head and neck cancer patients to measure the setup error and cumulative dose uncertainty of the cochlea. Methods: Data from 10 head and neck patients with 10 planning CTs and 52 Cone Beam CTs taken at time of treatment were used in this study. Patients were treated with conventional fractionation using an IMRT dose painting technique, most with 33 fractions. Weekly radiographic imaging was used to correct the patient setup. The authors used rigid registration of the planning CT and Cone Beam CT scans to find the translational and rotational setup errors, and the spatial setup errors of the cochlea. The planning CT was rotated and translated such that the cochlea positions match those seen in the cone beam scans, cochlea doses were recalculated and fractional doses accumulated. Uncertainties in the positions and cumulative doses of the cochlea were calculated with and without setup adjustments from radiographic imaging. Results: The mean setup error of the cochlea was 0.04 ± 0.33 or 0.06 ± 0.43 cm for RL, 0.09 ± 0.27 or 0.07 ± 0.48 cm for AP, and 0.00 ± 0.21 or −0.24 ± 0.45 cm for SI with and without radiographic imaging, respectively. Setup with radiographic imaging reduced the standard deviation of the setup error by roughly 1–2 mm. The uncertainty of the cochlea dose depends on the treatment plan and the relative positions of the cochlea and target volumes. Combining results for the left and right cochlea, the authors found the accumulated uncertainty of the cochlea dose per fraction was 4.82 (0.39–16.8) cGy, or 10.1 (0.8–32.4) cGy, with and without radiographic imaging, respectively; the percentage uncertainties relative to the planned doses were 4.32% (0.28%–9.06%) and 10.2% (0.7%–63.6%), respectively. Conclusions: Patient setup error introduces uncertainty in the position of the cochlea during radiation treatment. With the assistance of radiographic imaging during setup, the standard deviation of setup error reduced by 31%, 42%, and 54% in RL, AP, and SI direction, respectively, and consequently, the uncertainty of the mean dose to cochlea reduced more than 50%. The authors estimate that the effects of these uncertainties on the probability of hearing loss for an individual patient could be as large as 10%. PMID:24320510

Steroid therapy and the risk of osteonecrosis in SARS patients: a dose-response meta-analysis.

PubMed

Zhao, R; Wang, H; Wang, X; Feng, F

2017-03-01

This meta-analysis synthesized current evidence from 10 trials to evaluate the association between steroid therapy and osteonecrosis incidence in patients with severe acute respiratory syndrome (SARS). Our results suggest that higher cumulative doses and longer treatment durations of steroids are more likely to lead to the development of osteonecrosis in SARS patients. The link between steroid treatment and the risk of osteonecrosis in SARS patients remains unknown. The present meta-analysis aimed to examine the dose-response association between steroid therapy and osteonecrosis incidence in SARS patients. The sex differences in the development of steroid-induced osteonecrosis were also examined. We searched PubMed, Web of Science, CNKI, and WANFANG for studies that involved steroid therapy and reported osteonecrosis data in SARS patients. Two authors independently extracted the data from the individual studies, and the rate ratio (RR) of osteonecrosis was calculated using random-effect models. Ten studies with 1137 recovered SARS patients met the inclusion criteria. Close relationships between osteonecrosis incidence and both the cumulative dose and treatment duration of steroids were observed. The summary RR of osteonecrosis was 1.57 (95% confidence interval (CI) 1.30-1.89, p < 0.001) per 5.0 g increase in the cumulative dose of steroids and was 1.29 (95% CI 1.09-1.53, p = 0.003) for each 10-day increment of increase in treatment duration. The relationship was non-linear (p non-linear  < 0.001 and p non-linear  = 0.022). There were no significant differences in the risk of developing osteonecrosis between the male and female patients (RR 0.01, 95% CI -0.03 to 0.06, p = 0.582). SARS patients who received higher cumulative doses and longer treatment durations of steroids were more likely to develop osteonecrosis, and there were no sex differences in this dose-dependent side effect. Our findings suggest that it is important to reduce osteonecrosis risk by modifying the cumulative dose and the treatment duration of steroids in SARS patients.

The effects of intraperitoneal administration of the GABA(B) receptor agonist baclofen on food intake in CFLP and C57BL/6 mice.

PubMed

Ebenezer, Ivor S; Prabhaker, Monika

2007-08-13

The effects of the GABA(B) receptor agonist baclofen were investigated on food intake in non-deprived CFLP and C57BL/6 mice. In Experiment 1, baclofen (1-8 mg /kg) administered i.p. to CFLP mice, produced a dose-related increase in food intake. The 4 and 8 mg/kg doses produced significant increases in cumulative feeding when measure 120 min after administration (at least P < 0.05, in each case). In Experiment 2, baclofen (1-10 mg/kg), administered intraperitoneally (i.p.) to C57BL/6 mice, also produced a dose-related increase in food intake. The 4 mg/kg dose of baclofen significantly increased cumulative food intake at 60 min (P < 0.05), while the 2 and 4 mg/kg doses significantly increased cumulative food intake at 120 min (P < 0.01, in each case). The 10mg/kg dose was without effect. These data show that systemic administration of the GABA(B) agonist baclofen produces an increase in food consumption in two different strains of mice and extend previous observations made in rat to another rodent species.

The non-cancer mortality experience of male workers at British Nuclear Fuels plc, 1946–2005

PubMed Central

McGeoghegan, Dave; Binks, Keith; Gillies, Michael; Jones, Steve; Whaley, Steve

2008-01-01

Background Recent studies of the Hiroshima and Nagasaki A-bomb survivors, together with some (but not all) cohorts exposed occupationally or medically to ionizing radiation, have found an increasing trend in mortality from non-malignant disease with increasing radiation dose. The aim of this study was to establish whether such a trend could be found in a large cohort of employees in the UK nuclear industry. Methods The cohort comprised 64 937 individuals ever employed at the study sites between 1946 and 2002, followed up to 2005; radiation exposures as measured by personal dosimeters (‘film badges’) were available for 42 426 individuals classified as ‘radiation workers’. Poisson regression models were used to investigate the relationship between excess mortality rates and cumulative radiation exposure, using both relative and additive risk models. Results The cohort shows a pronounced ‘healthy worker’ effect. Overall, socio-economic status as indicated by employment status has a greater influence on mortality than does radiation exposure status. For male radiation workers, there is an apparent dose response for mortality from circulatory system disease [P < 0.001, ERR = 0.65 (90% CI 0.36–0.98) Sv−1]. However there is evidence for inhomogeneity in the apparent dose response (P = 0.016), arising principally at cumulative doses in excess of 300 mSv, when the four categories of employment and radiation exposure status are examined separately. Conclusions We have found evidence for an association between mortality from non-cancer causes of death, particularly circulatory system disease, and external exposure to ionizing radiation in this cohort. However, the tentative nature of biological mechanisms that might explain such an effect at low chronic doses and the above inhomogeneities in apparent dose–response, mean that the results of our analysis are not consistent with any simple causal interpretation. Further work is required to explain these inhomogeneities, and on the possible role of factors associated with socio-economic status and shift working, before any further conclusions can be drawn. PMID:18319298

Technical Note: scuda: A software platform for cumulative dose assessment.

PubMed

Park, Seyoun; McNutt, Todd; Plishker, William; Quon, Harry; Wong, John; Shekhar, Raj; Lee, Junghoon

2016-10-01

Accurate tracking of anatomical changes and computation of actually delivered dose to the patient are critical for successful adaptive radiation therapy (ART). Additionally, efficient data management and fast processing are practically important for the adoption in clinic as ART involves a large amount of image and treatment data. The purpose of this study was to develop an accurate and efficient Software platform for CUmulative Dose Assessment (scuda) that can be seamlessly integrated into the clinical workflow. scuda consists of deformable image registration (DIR), segmentation, dose computation modules, and a graphical user interface. It is connected to our image PACS and radiotherapy informatics databases from which it automatically queries/retrieves patient images, radiotherapy plan, beam data, and daily treatment information, thus providing an efficient and unified workflow. For accurate registration of the planning CT and daily CBCTs, the authors iteratively correct CBCT intensities by matching local intensity histograms during the DIR process. Contours of the target tumor and critical structures are then propagated from the planning CT to daily CBCTs using the computed deformations. The actual delivered daily dose is computed using the registered CT and patient setup information by a superposition/convolution algorithm, and accumulated using the computed deformation fields. Both DIR and dose computation modules are accelerated by a graphics processing unit. The cumulative dose computation process has been validated on 30 head and neck (HN) cancer cases, showing 3.5 ± 5.0 Gy (mean±STD) absolute mean dose differences between the planned and the actually delivered doses in the parotid glands. On average, DIR, dose computation, and segmentation take 20 s/fraction and 17 min for a 35-fraction treatment including additional computation for dose accumulation. The authors developed a unified software platform that provides accurate and efficient monitoring of anatomical changes and computation of actually delivered dose to the patient, thus realizing an efficient cumulative dose computation workflow. Evaluation on HN cases demonstrated the utility of our platform for monitoring the treatment quality and detecting significant dosimetric variations that are keys to successful ART.

Technical Note: SCUDA: A software platform for cumulative dose assessment

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

Park, Seyoun; McNutt, Todd; Quon, Harry

Purpose: Accurate tracking of anatomical changes and computation of actually delivered dose to the patient are critical for successful adaptive radiation therapy (ART). Additionally, efficient data management and fast processing are practically important for the adoption in clinic as ART involves a large amount of image and treatment data. The purpose of this study was to develop an accurate and efficient Software platform for CUmulative Dose Assessment (SCUDA) that can be seamlessly integrated into the clinical workflow. Methods: SCUDA consists of deformable image registration (DIR), segmentation, dose computation modules, and a graphical user interface. It is connected to our imagemore » PACS and radiotherapy informatics databases from which it automatically queries/retrieves patient images, radiotherapy plan, beam data, and daily treatment information, thus providing an efficient and unified workflow. For accurate registration of the planning CT and daily CBCTs, the authors iteratively correct CBCT intensities by matching local intensity histograms during the DIR process. Contours of the target tumor and critical structures are then propagated from the planning CT to daily CBCTs using the computed deformations. The actual delivered daily dose is computed using the registered CT and patient setup information by a superposition/convolution algorithm, and accumulated using the computed deformation fields. Both DIR and dose computation modules are accelerated by a graphics processing unit. Results: The cumulative dose computation process has been validated on 30 head and neck (HN) cancer cases, showing 3.5 ± 5.0 Gy (mean±STD) absolute mean dose differences between the planned and the actually delivered doses in the parotid glands. On average, DIR, dose computation, and segmentation take 20 s/fraction and 17 min for a 35-fraction treatment including additional computation for dose accumulation. Conclusions: The authors developed a unified software platform that provides accurate and efficient monitoring of anatomical changes and computation of actually delivered dose to the patient, thus realizing an efficient cumulative dose computation workflow. Evaluation on HN cases demonstrated the utility of our platform for monitoring the treatment quality and detecting significant dosimetric variations that are keys to successful ART.« less

Long-Term Dose-Dependent Agalsidase Effects on Kidney Histology in Fabry Disease.

PubMed

Skrunes, Rannveig; Tøndel, Camilla; Leh, Sabine; Larsen, Kristin Kampevold; Houge, Gunnar; Davidsen, Einar Skulstad; Hollak, Carla; van Kuilenburg, André B P; Vaz, Frédéric M; Svarstad, Einar

2017-09-07

Dose-dependent clearing of podocyte globotriaosylceramide has previously been shown in patients with classic Fabry disease treated with enzyme replacement. Our study evaluates the dose-dependent effects of agalsidase therapy in serial kidney biopsies of patients treated for up to 14 years. Twenty patients with classic Fabry disease (12 men) started enzyme replacement therapy at a median age of 21 (range =7-62) years old. Agalsidase- α or - β was prescribed for a median of 9.4 (range =5-14) years. The lower fixed dose group received agalsidase 0.2 mg/kg every other week throughout the follow-up period. The higher dose group received a range of agalsidase doses (0.2-1.0 mg/kg every other week). Dose changes were made due to disease progression, suboptimal effect, or agalsidase- β shortage. Serial kidney biopsies were performed along with clinical assessment and biomarkers and scored according to recommendations from the International Study Group of Fabry Nephropathy. No statistical differences were found in baseline or final GFR or albuminuria. Kidney biopsies showed significant reduction of podocyte globotriaosylceramide in both the lower fixed dose group (-1.39 [SD=1.04]; P =0.004) and the higher dose group (-3.16 [SD=2.39]; P =0.002). Podocyte globotriaosylceramide (Gb3) reduction correlated with cumulative agalsidase dose ( r =0.69; P =0.001). Arterial/arteriolar intima Gb3 cleared significantly in the higher dose group, all seven patients with baseline intimal Gb3 cleared the intima, one patient gained intimal Gb3 inclusions ( P =0.03), and medial Gb3 did not change statistically in either group. Residual plasma globotriaosylsphingosine levels remained higher in the lower fixed dose group (20.1 nmol/L [SD=11.9]) compared with the higher dose group (10.4 nmol/L [SD=8.4]) and correlated with cumulative agalsidase dose in men ( r =0.71; P =0.01). Reduction of podocyte globotriaosylceramide was found in patients with classic Fabry disease treated with long-term agalsidase on different dosing regimens, correlating with cumulative dose. Limited clearing of arterial/arteriolar globotriaosylceramide raises concerns regarding long-term vascular effects of current therapy. Residual plasma globotriaosylsphingosine correlated with cumulative dose in men. Copyright © 2017 by the American Society of Nephrology.

Radiation dose from common radiological investigations and cumulative exposure in children with cystic fibrosis: an observational study from a single UK centre

PubMed Central

Ward, Rebecca; Carroll, William D; Cunningham, Paula; Ho, Sheng-Ang; Jones, Mary; Lenney, Warren; Thompson, David

2017-01-01

Objectives Cumulative radiation exposure is associated with increased risk of malignancy. This is important in cystic fibrosis (CF) as frequent imaging is required to monitor disease progression and diagnose complications. Previous estimates of cumulative radiation are outdated as the imaging was performed on older equipment likely to deliver higher radiation. Our objectives were to determine the radiation dose delivered to children during common radiological investigations using modern equipment and to identify the number of such investigations performed in a cohort of children with CF to calculate their cumulative radiation exposure. Design, setting and participants Data including age at investigation and radiation exposure measured as estimated effective dose (EED) were collected on 2827 radiological studies performed on children at one UK paediatric centre. These were combined with the details of all radiological investigations performed on 65 children with CF attending the same centre to enable calculation of each child’s cumulative radiation exposure. Results The mean EED for the common radiological investigations varied according to age. The range was 0.01–0.02 mSv for chest X-rays, 0.03–0.11 mSv for abdominal X-rays, 0.57–1.69 mSv for CT chest, 2.9–3.9 mSv for abdominal and pelvic CT, 0.20–0.21 mSv for sinus CT and 0.15–0.52 mSv for fluoroscopy-guided procedures. The mean EED was three to five times higher for helical compared with axial chest CT scans. The mean annual cumulative EED for our cohort of children with CF was 0.15 mSv/year with an estimated cumulative paediatric lifetime EED (0–18 years) of 3.5 mSv. Conclusions This study provides up-to-date estimations of the radiation exposure when using common radiological investigations. These doses and the estimates of cumulative radiation exposure in children with CF are lower than previously reported. This reflects the reduced EED associated with modern equipment and the use of age-specific scanning protocols. PMID:28827272

Comparison of skin dose measurement using nanoDot® dosimeter and machine readings of radiation dose during cardiac catheterization in children

PubMed Central

Balaguru, Duraisamy; Rodriguez, Matthew; Leon, Stephanie; Wagner, Louis K; Beasley, Charles W; Sultzer, Andrew; Numan, Mohammed T

2018-01-01

Objectives: Direct measurement of skin dose of radiation for children using optically stimulated luminescence (OSL) technology using nanoDot® (Landauer, Glenwood, IL, USA). Background: Radiation dose is estimated as cumulative air kerma (AK) and dosearea product based on standards established for adult size patients. Body size of pediatric patients who undergo cardiac catheterization for congenital heart disease vary widely from newborn to adolescence. Direct, skindose measurement applying OSL technology may eliminate errors in the estimate. Materials and Methods: The nanoDot® (1 cm × 1 cm × flat plastic cassette) is applied to patient's skin using adhesive tape during cardiac catheterization and radiation skin doses were read within 24 hrs. nanoDot® values were compared to the currently available cumulative AK values estimated and displayed on fluoroscopy monitor. Results: A total of 12 children were studied, aged 4 months to 18 years (median 1.1 years) and weight range 5.3–86 kg (median 8.4 kg). nanoDot® readings ranged from 2.58 mGy to 424.8 mGy (median 84.1 mGy). Cumulative AK ranged from 16.2 mGy to 571.2 mGy (median 171.1 mGy). Linear correlation was noted between nanoDot® values and AK values (R2 = 0.88, R = 0.94). nanoDot® readings were approximately 65% of the estimated cumulative AK estimated using the International Electrotechnical Commission standards. Conclusions: Application of OSL technology using nanoDot® provides an alternative to directly measure fluoroscopic skin dose in children during cardiac catheterization. Our data show that the actual skin dose for children is approximately one-third lower than the AK estimated using international standards for adult size patients. PMID:29440825

Comparison of skin dose measurement using nanoDot® dosimeter and machine readings of radiation dose during cardiac catheterization in children.

PubMed

Balaguru, Duraisamy; Rodriguez, Matthew; Leon, Stephanie; Wagner, Louis K; Beasley, Charles W; Sultzer, Andrew; Numan, Mohammed T

2018-01-01

Direct measurement of skin dose of radiation for children using optically stimulated luminescence (OSL) technology using nanoDot ® (Landauer, Glenwood, IL, USA). Radiation dose is estimated as cumulative air kerma (AK) and dosearea product based on standards established for adult size patients. Body size of pediatric patients who undergo cardiac catheterization for congenital heart disease vary widely from newborn to adolescence. Direct, skindose measurement applying OSL technology may eliminate errors in the estimate. The nanoDot ® (1 cm × 1 cm × flat plastic cassette) is applied to patient's skin using adhesive tape during cardiac catheterization and radiation skin doses were read within 24 hrs. nanoDot ® values were compared to the currently available cumulative AK values estimated and displayed on fluoroscopy monitor. A total of 12 children were studied, aged 4 months to 18 years (median 1.1 years) and weight range 5.3-86 kg (median 8.4 kg). nanoDot® readings ranged from 2.58 mGy to 424.8 mGy (median 84.1 mGy). Cumulative AK ranged from 16.2 mGy to 571.2 mGy (median 171.1 mGy). Linear correlation was noted between nanoDot® values and AK values ( R 2 = 0.88, R = 0.94). nanoDot® readings were approximately 65% of the estimated cumulative AK estimated using the International Electrotechnical Commission standards. Application of OSL technology using nanoDot® provides an alternative to directly measure fluoroscopic skin dose in children during cardiac catheterization. Our data show that the actual skin dose for children is approximately one-third lower than the AK estimated using international standards for adult size patients.

SU-E-J-181: Effect of Prostate Motion On Combined Brachytherapy and External Beam Dose Based On Daily Motion of the Prostate

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

Narayana, V; McLaughlin, P; University of Michigan, Ann Arbor, MI

2015-06-15

Purpose: In this study, the adequacy of target expansions on the combined external beam and implant dose was examined based on the measured daily motion of the prostate. Methods: Thirty patients received an I–125 prostate implant prescribed to dose of 90Gy. This was followed by external beam to deliver a dose of 90Gyeq (external beam equivalent) to the prostate over 25 to 30 fractions. An ideal IMRT plan was developed by optimizing the external beam dose based on the delivered implant dose. The implant dose was converted to an equivalent external beam dose using the linear quadratic model. Patients weremore » set up on the treatment table by daily orthogonal imaging and aligning the marker seeds in the prostate. Orthogonal images were obtained at the end of treatment to assess prostate intrafraction motion. Based on the observed motion of the markers between the initial and final images, 5 individual plans showing the actual dose delivered to the patient were calculated. A final true dose distribution was established based on summing the implant dose and the 5 external beam plans. Dose to the prostate, seminal vesicles, lymphnodes and normal tissues, rectal wall, urethra and lower sphincter were calculated and compared to ideal. On 18 patients who were sexually active, dose to the corpus cavernosum and internal pudendal artery was also calculated. Results: The average prostate motion in 3 orthogonal directions was less than 1 mm with a standard deviation of less than +2 mm. Dose and volume parameters showed that there was no decrease in dose to the targets and a marginal decrease in dose to in normal tissues. Conclusion: Dose delivered by seed implant moves with the prostate, decreasing the impact of intrafractions dose movement on actual dose delivered. Combined brachytherapy and external beam dose delivered to the prostate was not sensitive to prostate motion.« less

The addition of low-dose-rate brachytherapy and androgen-deprivation therapy decreases biochemical failure and prostate cancer death compared with dose-escalated external-beam radiation therapy for high-risk prostate cancer.

PubMed

Shilkrut, Mark; Merrick, Gregory S; McLaughlin, P William; Stenmark, Matthew H; Abu-Isa, Eyad; Vance, Sean M; Sandler, Howard M; Feng, Felix Y; Hamstra, Daniel A

2013-02-01

The objective of this study was to determine whether the addition of low-dose-rate brachytherapy or androgen-deprivation therapy (ADT) improves clinical outcome in patients with high-risk prostate cancer (HiRPCa) who received dose-escalated radiotherapy (RT). Between 1995 and 2010, 958 patients with HiRPCa were treated at Schiffler Cancer Center (n = 484) or at the University of Michigan (n = 474) by receiving either dose-escalated external-beam RT (EBRT) (n = 510; minimum prescription dose, 75 grays [Gy]; median dose, 78 Gy) or combined-modality RT (CMRT) consisting of (103) Pd implants (n = 369) or (125) I implants (n = 79) both with pelvic irradiation (median prescription dose, 45 Gy). The cumulative incidences of biochemical failure (BF) and prostate cancer-specific mortality (PCSM) were estimated by using the Kaplan-Meier method and Fine and Gray regression analysis. The median follow-up was 63.2 months (interquartile range, 35.4-99.0 months), and 250 patients were followed for >8 years. Compared with CMRT, patients who received EBRT had higher prostate-specific antigen levels, higher tumor classification, lower Gleason sum, and more frequent receipt of ADT for a longer duration. The 8-year incidence BF and PCSM among patients who received EBRT was 40% (standard error, 38%-44%) and 13% (standard error, 11%-15%) compared with 14% (standard error, 12%-16%; P < .0001) and 7% (standard error 6%-9%; P = .003) among patients who received CMRT. On multivariate analysis, the hazard ratios (HRs) for BF and PCSM were 0.35 (95% confidence interval [CI], 0.23-0.52; P < .0001) and 0.41 (95% CI, 0.23-0.75; P < .003), favoring CMRT. Increasing duration of ADT predicted decreased BF (P = .04) and PCSM (P = .001), which was greatest with long-term ADT (BF: HR, 0.33; P < .0001; 95% CI, 0.21-0.52; PCSM: HR, 0.30; P = .001; 95% CI, 0.15-0.6) even in the subgroup that received CMRT. In this retrospective comparison, both low-dose-rate brachytherapy boost and ADT were associated with decreased risks of BF and PCSM compared with EBRT. Copyright © 2012 American Cancer Society.

A Monte Carlo study of the impact of the choice of rectum volume definition on estimates of equivalent uniform doses and the volume parameter

NASA Astrophysics Data System (ADS)

Kvinnsland, Yngve; Muren, Ludvig Paul; Dahl, Olav

2004-08-01

Calculations of normal tissue complication probability (NTCP) values for the rectum are difficult because it is a hollow, non-rigid, organ. Finding the true cumulative dose distribution for a number of treatment fractions requires a CT scan before each treatment fraction. This is labour intensive, and several surrogate distributions have therefore been suggested, such as dose wall histograms, dose surface histograms and histograms for the solid rectum, with and without margins. In this study, a Monte Carlo method is used to investigate the relationships between the cumulative dose distributions based on all treatment fractions and the above-mentioned histograms that are based on one CT scan only, in terms of equivalent uniform dose. Furthermore, the effect of a specific choice of histogram on estimates of the volume parameter of the probit NTCP model was investigated. It was found that the solid rectum and the rectum wall histograms (without margins) gave equivalent uniform doses with an expected value close to the values calculated from the cumulative dose distributions in the rectum wall. With the number of patients available in this study the standard deviations of the estimates of the volume parameter were large, and it was not possible to decide which volume gave the best estimates of the volume parameter, but there were distinct differences in the mean values of the values obtained.

SU-E-J-106: The Use of Deformable Image Registration with Cone-Beam CT for a Better Evaluation of Cumulative Dose to Organs

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

Fillion, O; Gingras, L; Archambault, L

2015-06-15

Purpose: The knowledge of dose accumulation in the patient tissues in radiotherapy helps in determining the treatment outcomes. This project aims at providing a workflow to map cumulative doses that takes into account interfraction organ motion without the need for manual re-contouring. Methods: Five prostate cancer patients were studied. Each patient had a planning CT (pCT) and 5 to 13 CBCT scans. On each series, a physician contoured the prostate, rectum, bladder, seminal vesicles and the intestine. First, a deformable image registration (DIR) of the pCTs onto the daily CBCTs yielded registered CTs (rCT) . This rCT combined the accuratemore » CT numbers of the pCT with the daily anatomy of the CBCT. Second, the original plans (220 cGy per fraction for 25 fractions) were copied on the rCT for dose re-calculation. Third, the DIR software Elastix was used to find the inverse transform from the rCT to the pCT. This transformation was then applied to the rCT dose grid to map the dose voxels back to their pCT location. Finally, the sum of these deformed dose grids for each patient was applied on the pCT to calculate the actual dose delivered to organs. Results: The discrepancy between the planned D98 and D2 and these indices re-calculated on the rCT, are, on average, of −1 ± 1 cGy and 1 ± 2 cGy per fraction, respectively. For fractions with large anatomical motion, the D98 discrepancy on the re-calculated dose grid mapped onto the pCT can raise to −17 ± 4 cGy. The obtained cumulative dose distributions illustrate the same behavior. Conclusion: This approach allowed the evaluation of cumulative doses to organs with the help of uncontoured daily CBCT scans. With this workflow, the easy evaluation of doses delivered for EBRT treatments could ultimately lead to a better follow-up of prostate cancer patients.« less

SU-C-BRD-04: Comparison of Shallow Fluence to Deep Point Dose Measurements for Spine VMAT SBRT Patient-Specific QA

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

Cheung, J; Held, M; Morin, O

2015-06-15

Purpose: To investigate the sensitivity of traditional gamma-index-based fluence measurements for patient-specific measurements in VMAT delivered spine SBRT. Methods: The ten most recent cases for spine SBRT were selected. All cases were planned with Eclipse RapidArc for a TrueBeam STx. The delivery was verified using a point dose measurement with a Pinpoint 3D micro-ion chamber in a Standard Imaging Stereotactic Dose Verification Phantom. Two points were selected for each case, one within the target in a low dose-gradient region and one in the spinal cord. Measurements were localized using on-board CBCT. Cumulative and separate arc measurements were acquired with themore » ArcCheck and assessed using the SNC patient software with a 3%/3mm and 2%/2mm gamma analysis with global normalization and a 10% dose threshold. Correlations between data were determined using the Pearson Product-Moment Correlation. Results: For our cohort of patients, the measured doses were higher than calculated ranging from 2.2%–9.7% for the target and 1.0%–8.2% for the spinal cord. There was strong correlation between 3%/3mm and 2%/2mm passing rates (r=0.91). Moderate correlation was found between target and cord dose with a weak fit (r=0.67, R-Square=0.45). The cumulative ArcCheck measurements showed poor correlation with the measured point doses for both the target and cord (r=0.20, r=0.35). If the arcs are assessed separately with an acceptance criteria applied to the minimum passing rate between all arcs, a moderate negative correlation was found for the target and cord (r=−0.48, r= −0.71). The case with the highest dose difference (9.7%) received a passing rate of 97.2% for the cumulative arcs and 87.8% for the minimum with separate arcs. Conclusion: Our data suggest that traditional passing criteria using ArcCheck with cumulative measurements do not correlate well with dose errors. Separate arc analysis shows better correlation but may still miss large dose errors. Point dose verifications are recommended.« less

Schooling and National Income: How Large Are the Externalities?

ERIC Educational Resources Information Center

Breton, Theodore R.

2010-01-01

This paper uses a new data-set for cumulative national investment in formal schooling and a new instrument for schooling to estimate the national return on investment in 61 countries. These estimates are combined with data on the private rate of return on investment in schooling to estimate the external rate of return. In 1990 the external rate of…

Effects of B Vitamins Overload on Plasma Insulin Level and Hydrogen Peroxide Generation in Rats.

PubMed

Sun, Wuping; Zhai, Mingzhu; Zhou, Qian; Qian, Chengrui; Jiang, Changyu

2017-08-31

It has been reported that nicotinamide-overload induces oxidative stress associated with insulin resistance, the key feature of type 2 diabetes mellitus (T2DM). This study aimed to investigate the effects of B vitamins in T2DM. Glucose tolerance tests were carried out in adult Sprague-Dawley rats treated with or without cumulative doses of B vitamins. More specifically, insulin tolerance tests were also carried out in adult Sprague-Dawley rats treated with or without cumulative doses of Vitamin B3. We found that cumulative Vitamin B1 and Vitamin B3 administration significantly increased the plasma H₂O₂ levels associated with high insulin levels. Only Vitamin B3 reduced muscular and hepatic glycogen contents. Cumulative administration of nicotinic acid, another form of Vitamin B3, also significantly increased plasma insulin level and H₂O₂ generation. Moreover, cumulative administration of nicotinic acid or nicotinamide impaired glucose metabolism. This study suggested that excess Vitamin B1 and Vitamin B3 caused oxidative stress and insulin resistance.

Cumulative adversity in childhood and emergent risk factors for long-term health.

PubMed

Slopen, Natalie; Koenen, Karestan C; Kubzansky, Laura D

2014-03-01

To examine whether and when effects of cumulative adversity in the first 7 years of life are evident in relation to 3 childhood markers of risk for poor adult physical health. The study data are from an English birth cohort. Parental reports of 8 social risk factors were obtained during the child's first 7 years, and scores were created to reflect cumulative adversity at 4 developmental periods. At age 7 and 11 years, weight, height, and blood pressure (BP) were measured by clinic staff, and caregivers reported behavior problems. Linear regression was used to estimate associations of cumulative adversity with each outcome (n = 4361) and changes in these outcomes between 7 and 11 years (n = 3348). At age 7 years, mean adversity and chronic exposure to high adversity were associated with elevated body mass index (BMI) and internalizing and externalizing symptoms (P < .05), but not elevated BP. Adversity in all developmental periods was associated with elevated numbers of internalizing and externalizing symptoms (P < .0001), but associations were less robust for BMI. Adversity did not predict change in BMI or BP between age 7 and 11 years, however, it predicted increases in internalizing and externalizing symptoms (P < .0001). Cumulative adversity was associated with BMI and behavior problems at age 7 years, and our data indicate that timing and chronicity of exposure to adversity differentially influence diverse indicators of long-term health risk commonly measured in childhood. This research suggests the hypothesis that interventions to address adversity could reduce the development of multiple chronic disease risk factors and limit their effects on health. Copyright © 2014 Mosby, Inc. All rights reserved.

Dose fractionated gamma knife radiosurgery for large arteriovenous malformations on daily or alternate day schedule outside the linear quadratic model: Proof of concept and early results. A substitute to volume fractionation.

PubMed

Mukherjee, Kanchan Kumar; Kumar, Narendra; Tripathi, Manjul; Oinam, Arun S; Ahuja, Chirag K; Dhandapani, Sivashanmugam; Kapoor, Rakesh; Ghoshal, Sushmita; Kaur, Rupinder; Bhatt, Sandeep

2017-01-01

To evaluate the feasibility, safety and efficacy of dose fractionated gamma knife radiosurgery (DFGKRS) on a daily schedule beyond the linear quadratic (LQ) model, for large volume arteriovenous malformations (AVMs). Between 2012-16, 14 patients of large AVMs (median volume 26.5 cc) unsuitable for surgery or embolization were treated in 2-3 of DFGKRS sessions. The Leksell G frame was kept in situ during the whole procedure. 86% (n = 12) patients had radiologic evidence of bleed, and 43% (n = 6) had presented with a history of seizures. 57% (n = 8) patients received a daily treatment for 3 days and 43% (n = 6) were on an alternate day (2 fractions) regimen. The marginal dose was split into 2 or 3 fractions of the ideal prescription dose of a single fraction of 23-25 Gy. The median follow up period was 35.6 months (8-57 months). In the three-fraction scheme, the marginal dose ranged from 8.9-11.5 Gy, while in the two-fraction scheme, the marginal dose ranged from 11.3-15 Gy at 50% per fraction. Headache (43%, n = 6) was the most common early postoperative complication, which was controlled with short course steroids. Follow up evaluation of at least three years was achieved in seven patients, who have shown complete nidus obliteration in 43% patients while the obliteration has been in the range of 50-99% in rest of the patients. Overall, there was a 67.8% reduction in the AVM volume at 3 years. Nidus obliteration at 3 years showed a significant rank order correlation with the cumulative prescription dose (p 0.95, P value 0.01), with attainment of near-total (more than 95%) obliteration rates beyond 29 Gy of the cumulative prescription dose. No patient receiving a cumulative prescription dose of less than 31 Gy had any severe adverse reaction. In co-variate adjusted ordinal regression, only the cumulative prescription dose had a significant correlation with common terminology criteria for adverse events (CTCAE) severity (P value 0.04), independent of age, AVM volume, number of fractions and volume of brain receiving atleast 8 Gy of radiation. DFGKRS is feasible for large AVMs with a fair nidus obliteration rate and acceptable toxicity. Cumulative prescription dose seems to be the most significant independent predictor for outcome following DFGKRS with 29-30 Gy resulting in a fair nidus obliteration with least adverse events.

10 CFR 20.1203 - Determination of external dose from airborne radioactive material.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Determination of external dose from airborne radioactive material. 20.1203 Section 20.1203 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1203 Determination of external dose from airborne radioactive...

10 CFR 20.1203 - Determination of external dose from airborne radioactive material.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Determination of external dose from airborne radioactive material. 20.1203 Section 20.1203 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1203 Determination of external dose from airborne radioactive...

10 CFR 20.1203 - Determination of external dose from airborne radioactive material.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Determination of external dose from airborne radioactive material. 20.1203 Section 20.1203 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1203 Determination of external dose from airborne radioactive...

10 CFR 20.1203 - Determination of external dose from airborne radioactive material.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Determination of external dose from airborne radioactive material. 20.1203 Section 20.1203 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1203 Determination of external dose from airborne radioactive...

10 CFR 20.1203 - Determination of external dose from airborne radioactive material.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Determination of external dose from airborne radioactive material. 20.1203 Section 20.1203 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1203 Determination of external dose from airborne radioactive...

Cumulative Risk and Adolescent's Internalizing and Externalizing Problems: The Mediating Roles of Maternal Responsiveness and Self-Regulation

ERIC Educational Resources Information Center

Doan, Stacey N.; Fuller-Rowell, Thomas E.; Evans, Gary W.

2012-01-01

The purpose of the present study was to examine longitudinal associations among maternal responsiveness, self-regulation, and behavioral adjustment in adolescents. The authors used structural equation modeling to test a model that demonstrates that the effects of early cumulative risk on behavioral problems is mediated by maternal responsiveness…

Intravenous Iron Therapy in Patients with Iron Deficiency Anemia: Dosing Considerations

PubMed Central

Myers, Jennifer; Goodnough, Lawrence Tim

2015-01-01

Objective. To provide clinicians with evidence-based guidance for iron therapy dosing in patients with iron deficiency anemia (IDA), we conducted a study examining the benefits of a higher cumulative dose of intravenous (IV) iron than what is typically administered. Methods. We first individually analyzed 5 clinical studies, averaging the total iron deficit across all patients utilizing a modified Ganzoni formula; we then similarly analyzed 2 larger clinical studies. For the second of the larger studies (Study 7), we also compared the efficacy and retreatment requirements of a cumulative dose of 1500 mg ferric carboxymaltose (FCM) to 1000 mg iron sucrose (IS). Results. The average iron deficit was calculated to be 1531 mg for patients in Studies 1–5 and 1392 mg for patients in Studies 6-7. The percentage of patients who were retreated with IV iron between Days 56 and 90 was significantly (p < 0.001) lower (5.6%) in the 1500 mg group, compared to the 1000 mg group (11.1%). Conclusions. Our data suggests that a total cumulative dose of 1000 mg of IV iron may be insufficient for iron repletion in a majority of patients with IDA and a dose of 1500 mg is closer to the actual iron deficit in these patients. PMID:26257955

Assessment of radiation exposure from cesium-137 contaminated roads for epidemiological studies in Seoul, Korea.

PubMed

Lee, Yun-Keun; Ju, Young-Su; Lee, Won Jin; Hwang, Seung Sik; Yim, Sang-Hyuk; Yoo, Sang-Chul; Lee, Jieon; Choi, Kyung-Hwa; Burm, Eunae; Ha, Mina

2015-01-01

We aimed to assess the radiation exposure for epidemiologic investigation in residents exposed to radiation from roads that were accidentally found to be contaminated with radioactive cesium-137 ((137)Cs) in Seoul. Using information regarding the frequency and duration of passing via the (137)Cs contaminated roads or residing/working near the roads from the questionnaires that were obtained from 8875 residents and the measured radiation doses reported by the Nuclear Safety and Security Commission, we calculated the total cumulative dose of radiation exposure for each person. Sixty-three percent of the residents who responded to the questionnaire were considered as ever-exposed and 1% of them had a total cumulative dose of more than 10 mSv. The mean (minimum, maximum) duration of radiation exposure was 4.75 years (0.08, 11.98) and the geometric mean (minimum, maximum) of the total cumulative dose was 0.049 mSv (<0.001, 35.35) in the exposed. An individual exposure assessment was performed for an epidemiological study to estimate the health risk among residents living in the vicinity of (137)Cs contaminated roads. The average exposure dose in the exposed people was less than 5% of the current guideline.

Investigation of dose characteristics in three-dimensional MAGAT-type polymer gel dosimetry with MSE MR imaging

NASA Astrophysics Data System (ADS)

Lee, Jason J. S.; Tsai, Chia-Jung; Lo, Man-Kuok; Huang, Yung-Hui; Chen, Chien-Chuan; Wu, Jay; Tyan, Yeu-Sheng; Wu, Tung-Hsin

2008-05-01

A new type of normoxic polymer gel dosimeter, named MAGAT responses well to absorbed dose even when manufacturing in the presence of normal levels of oxygen. The aim of this study was to evaluate dose response, diffusion effect and cumulated dose response under multiple fractional irradiations of the MAGAT gel dosimeter using Multiple Spin-Echo (MSE) Magnetic Resonance (MR) sequence. Dose response was performed by irradiating MAGAT-gel-filled testing vials with a 6 MV linear accelerator and a linear relationship was present with doses from 0 to 6 Gy, but gradually, a bi-exponential function result was obtained with given doses up to 20 Gy. No significant difference in dose response was present between single and cumulated doses (p > 0.05). For study of diffusion effect, edge sharpness of the R2 map imaging between two split doses was smaller than 1 cm of dose profile penumbra between 20% and 80%. In conclusion, the MAGAT polymer gel dosimeter with MSE MR imaging is a promising method for dose verification in clinical radiation therapy practice.

Three-Dimensional Radiobiologic Dosimetry: Application of Radiobiologic Modeling to Patient-Specific 3-Dimensional Imaging–Based Internal Dosimetry

PubMed Central

Prideaux, Andrew R.; Song, Hong; Hobbs, Robert F.; He, Bin; Frey, Eric C.; Ladenson, Paul W.; Wahl, Richard L.; Sgouros, George

2010-01-01

Phantom-based and patient-specific imaging-based dosimetry methodologies have traditionally yielded mean organ-absorbed doses or spatial dose distributions over tumors and normal organs. In this work, radiobiologic modeling is introduced to convert the spatial distribution of absorbed dose into biologically effective dose and equivalent uniform dose parameters. The methodology is illustrated using data from a thyroid cancer patient treated with radioiodine. Methods Three registered SPECT/CT scans were used to generate 3-dimensional images of radionuclide kinetics (clearance rate) and cumulated activity. The cumulated activity image and corresponding CT scan were provided as input into an EGSnrc-based Monte Carlo calculation: The cumulated activity image was used to define the distribution of decays, and an attenuation image derived from CT was used to define the corresponding spatial tissue density and composition distribution. The rate images were used to convert the spatial absorbed dose distribution to a biologically effective dose distribution, which was then used to estimate a single equivalent uniform dose for segmented volumes of interest. Equivalent uniform dose was also calculated from the absorbed dose distribution directly. Results We validate the method using simple models; compare the dose-volume histogram with a previously analyzed clinical case; and give the mean absorbed dose, mean biologically effective dose, and equivalent uniform dose for an illustrative case of a pediatric thyroid cancer patient with diffuse lung metastases. The mean absorbed dose, mean biologically effective dose, and equivalent uniform dose for the tumor were 57.7, 58.5, and 25.0 Gy, respectively. Corresponding values for normal lung tissue were 9.5, 9.8, and 8.3 Gy, respectively. Conclusion The analysis demonstrates the impact of radiobiologic modeling on response prediction. The 57% reduction in the equivalent dose value for the tumor reflects a high level of dose nonuniformity in the tumor and a corresponding reduced likelihood of achieving a tumor response. Such analyses are expected to be useful in treatment planning for radionuclide therapy. PMID:17504874

Tolerance of the Brachial Plexus to High-Dose Reirradiation

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

Chen, Allen M., E-mail: achen5@kumc.edu; Yoshizaki, Taeko; Velez, Maria A.

Purpose: To study the tolerance of the brachial plexus to high doses of radiation exceeding historically accepted limits by analyzing human subjects treated with reirradiation for recurrent tumors of the head and neck. Methods and Materials: Data from 43 patients who were confirmed to have received overlapping dose to the brachial plexus after review of radiation treatment plans from the initial and reirradiation courses were used to model the tolerance of this normal tissue structure. A standardized instrument for symptoms of neuropathy believed to be related to brachial plexus injury was utilized to screen for toxicity. Cumulative dose was calculatedmore » by fusing the initial dose distributions onto the reirradiation plan, thereby creating a composite plan via deformable image registration. The median elapsed time from the initial course of radiation therapy to reirradiation was 24 months (range, 3-144 months). Results: The dominant complaints among patients with symptoms were ipsilateral pain (54%), numbness/tingling (31%), and motor weakness and/or difficulty with manual dexterity (15%). The cumulative maximum dose (Dmax) received by the brachial plexus ranged from 60.5 Gy to 150.1 Gy (median, 95.0 Gy). The cumulative mean (Dmean) dose ranged from 20.2 Gy to 111.5 Gy (median, 63.8 Gy). The 1-year freedom from brachial plexus–related neuropathy was 67% and 86% for subjects with a cumulative Dmax greater than and less than 95.0 Gy, respectively (P=.05). The 1-year complication-free rate was 66% and 87%, for those reirradiated within and after 2 years from the initial course, respectively (P=.06). Conclusion: The development of brachial plexus–related symptoms was less than expected owing to repair kinetics and to the relatively short survival of the subject population. Time-dose factors were demonstrated to be predictive of complications.« less

Relationships between iron dose, hospitalizations and mortality in incident haemodialysis patients: a propensity-score matched approach.

PubMed

Varas, Javier; Ramos, Rosa; Aljama, Pedro; Pérez-García, Rafael; Moreso, Francesc; Pinedo, Miguel; Ignacio Merello, José; Stuard, Stefano; Canaud, Bernard; Martín-Malo, Alejandro

2018-01-01

Intravenous iron management is common in the haemodialysis population. However, the safest dosing strategy remains uncertain, in terms of the risk of hospitalization and mortality. We aimed to determine the effects of cumulative monthly iron doses on mortality and hospitalization. This multicentre observational retrospective propensity-matched score study included 1679 incident haemodialysis patients. We measured baseline demographic variables, haemodialysis clinical parameters and laboratory analytical values. We compared outcomes among quartiles of cumulative iron dose (mg/kg/month). We implemented propensity-score matching (PSM) to reduce confounding due to indication. In the PSM cohort (330 patients), we compared outcomes between groups that received cumulative iron doses above and below 5.66 mg/kg/month. Kaplan-Meier analyses showed that the high iron dose group had significantly worse survival than the low iron dose group. A univariate analysis indicated that the monthly iron dose could significantly predict mortality. However, a multivariate regression did not confirm that finding. The multivariate regression analysis revealed that iron doses  >5.58 mg/kg/month were not associated with elevated mortality risk, but they were associated with elevated risks of all-cause and cardiovascular-related hospitalizations. These results were ratified in the PSM population. Intravenous iron administration is advisable for maintaining haemoglobin levels in patients that receive haemodialysis. Our data suggested that large monthly iron doses, adjusted for body weight, were associated with more hospitalizations, but not with mortality or infection-related hospitalizations. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Addressing as low as reasonably achievable (ALARA) issues: investigation of worker collective external and extremity dose data

DOE PAGES

Cournoyer, Michael Edward; Costigan, Stephen Andrew; Schreiber, Stephen Bruce

2017-03-17

Plutonium emits both neutrons and photons and when it is stored or handled inside a glovebox, both photons and neutrons are significant external radiation hazards. Doses to the extremities are usually dominated by gamma radiation in typical plutonium glovebox operations. Excess external dose can generates stochastic effects consisting of cancer and benign tumors in some organs. Direct doses from radiation sources external to the body are measured by thermoluminescent dosimeters (TLDs) placed on the glovebox worker between the neck and waist. Wrist dosimeters are used to assess externally penetrating radiation including neutrons and provide an estimate of neutron radiation exposuremore » to the extremities. Both TLDs and wrist dosimeters are processed monthly for most glovebox workers. Here, worker collective extremity and external dose data have been analyzed to prevent and mitigate external radiation events through the use of Lean Manufacturing and Six Sigma business practices (LSS). Employing LSS, statistically significant variations (trends) are identified in worker collective extremity and external dose data. Finally, the research results presented in this paper are pivotal to the ultimate focus of this program, which is to minimize external radiation events.« less

Addressing as low as reasonably achievable (ALARA) issues: investigation of worker collective external and extremity dose data

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

Cournoyer, Michael Edward; Costigan, Stephen Andrew; Schreiber, Stephen Bruce

Plutonium emits both neutrons and photons and when it is stored or handled inside a glovebox, both photons and neutrons are significant external radiation hazards. Doses to the extremities are usually dominated by gamma radiation in typical plutonium glovebox operations. Excess external dose can generates stochastic effects consisting of cancer and benign tumors in some organs. Direct doses from radiation sources external to the body are measured by thermoluminescent dosimeters (TLDs) placed on the glovebox worker between the neck and waist. Wrist dosimeters are used to assess externally penetrating radiation including neutrons and provide an estimate of neutron radiation exposuremore » to the extremities. Both TLDs and wrist dosimeters are processed monthly for most glovebox workers. Here, worker collective extremity and external dose data have been analyzed to prevent and mitigate external radiation events through the use of Lean Manufacturing and Six Sigma business practices (LSS). Employing LSS, statistically significant variations (trends) are identified in worker collective extremity and external dose data. Finally, the research results presented in this paper are pivotal to the ultimate focus of this program, which is to minimize external radiation events.« less

External-beam Co-60 radiotherapy for canine nasal tumors: a comparison of survival by treatment protocol.

PubMed

Yoon, J H; Feeney, D A; Jessen, C R; Walter, P A

2008-02-01

A retrospective analysis of survival times in dogs with intranasal tumors was performed comparing those treated using hypofractionated or full course Co-60 radiotherapy protocols alone or with surgical adjuvant therapy and those receiving no radiation treatment. One hundred thirty-nine dogs presented to the University of Minnesota Veterinary Medical Center for treatment of histologically-confirmed nasal neoplasia between July 1983 and October 2001 met the criteria for review. Statistically analyzed parameters included age at diagnosis, tumor histologic classification, fractionation schedule (number of treatments, and number of treatment days/week) (classified as hypofractionated if 2 or less treatments/week); calculated minimum tumor dose/fraction; calculated total minimum tumor dose (classified as hypofractionated if less than 37 Gy in six or fewer fractions); number of radiotherapy portals, a treatment gap of more than 7 days in a full course (3-5 treatments/week, 3-3.5 week treatment time) radiotherapy protocol, the influence of eye shields on survival following single portal DV fields, the survey radiographic extent of the disease, and the presence or absence of cytoreductive surgery. There was a significant relationship only between protocols using 3 or more treatments/week and at least 37 Gy cumulative minimum tumor dose and survival. However, there was no significant relationship between either total minimum tumor dose or dose/fraction and survival and there were no significant relationships between survival and any of the other variables analyzed including tumor histologic type.

A case study of IMRT planning (Plan B) subsequent to a previously treated IMRT plan (Plan A)

NASA Astrophysics Data System (ADS)

Cao, F.; Leong, C.; Schroeder, J.; Lee, B.

2014-03-01

Background and purpose: Treatment of the contralateral neck after previous ipsilateral intensity modulated radiation therapy (IMRT) for head and neck cancer is a challenging problem. We have developed a technique that limits the cumulative dose to the spinal cord and brainstem while maximizing coverage of a planning target volume (PTV) in the contralateral neck. Our case involves a patient with right tonsil carcinoma who was given ipsilateral IMRT with 70Gy in 35 fractions (Plan A). A left neck recurrence was detected 14 months later. The patient underwent a neck dissection followed by postoperative left neck radiation to a dose of 66 Gy in 33 fractions (Plan B). Materials and Methods: The spinal cord-brainstem margin (SCBM) was defined as the spinal cord and brainstem with a 1.0 cm margin. Plan A was recalculated on the postoperative CT scan but the fluence outside of SCBM was deleted. A further modification of Plan A resulted in a base plan that was summed with Plan B to evaluate the cumulative dose received by the spinal cord and brainstem. Plan B alone was used to evaluate for coverage of the contralateral neck PTV. Results: The maximum cumulative doses to the spinal cord with 0.5cm margin and brainstem with 0.5cm margin were 51.96 Gy and 45.60 Gy respectively. For Plan B, 100% of the prescribed dose covered 95% of PTVb1. Conclusion: The use of a modified ipsilateral IMRT plan as a base plan is an effective way to limit the cumulative dose to the spinal cord and brainstem while enabling coverage of a PTV in the contralateral neck.

Influence of lake trophic structure on iodine-131 accumulation and subsequent cumulative radiation dose to trout thyroids.

PubMed

Martinez, Nicole E; Johnson, Thomas E; Pinder, John E

2014-05-01

Iodine-131 is a major component of the atmospheric releases following reactor accidents, and the passage of (131)I through food chains from grass to human thyroids has been extensively studied. By comparison, the fate and effects of (131)I deposition onto lakes and other aquatic systems have been less studied. In this study we: (1) reanalyze 1960s data from experimental releases of (131)I into two small lakes; (2) compare the effects of differences in lake trophic structures on the accumulation of (131)I by fish; (3) relate concentrations in fish and fish tissues to that in the water column using empirically estimated uptake (L kg(-1) d(-1)) and loss (d(-1)) parameters; and (4) show that the largest concentrations in the thyroids of trout (Oncorhynchus mykiss) may occur from 8 to 32 days after initial release. Iodine-131 concentration in trout thyroids at 30-days post release may be >1000 times that in the water. Estimates of cumulative radiation dose (mGy) to thyroids computed using an anatomically-appropriate model of trout thyroid structure within the Monte Carlo N-particle modeling software predicted cumulative thyroid doses that increased approximately linearly after the first 8 days and resulted in 32-day cumulative thyroid doses that ranged from 6 mGy g(-1) to 18 mGy g(-1) per 1 Bq mL(-1) of initial (131)I in the water depending upon fish size. The majority of this dose is due to beta emissions, and the dose varies with positions in the thyroid tissue. Copyright © 2013 Elsevier Ltd. All rights reserved.

Leukaemia mortality and low-dose ionising radiation in the WISMUT uranium miner cohort (1946-2013).

PubMed

Kreuzer, Michaela; Sobotzki, Christina; Fenske, Nora; Marsh, James W; Schnelzer, Maria

2017-03-01

To examine the risk of death from leukaemia in relation to occupational chronic low-level external and internal radiation exposure in a cohort of 58 972 former German uranium miners with mortality follow-up from 1946 to 2013. The red bone marrow (RBM) dose from low-linear energy transfer (LET) (mainly external γ-radiation) and high-LET (mainly radon gas) radiation was estimated based on a job-exposure matrix and biokinetic/dosimetric models. Linear excess relative risks (ERR) and 95% CIs were estimated via Poisson regression for chronic lymphatic leukaemia (CLL) and non-CLL. The mean cumulative low-LET and high-LET RBM doses among the 86% radiation-exposed workers were 48 and 9 mGy, respectively. There was a positive non-significant dose-response for mortality from non-CLL (n=120) in relation to low-LET (ERR/Gy=2.18; 95% CI -0.41 to 6.37) and high-LET radiation (ERR/Gy=16.65; 95% -1.13 to 46.75). A statistically significant excess was found for the subgroup chronic myeloid leukaemia (n=31) in relation to low-LET radiation (ERR/Gy=7.20; 95% CI 0.48 to 24.54) and the subgroup myeloid leukaemia (n=99) (ERR/Gy=26.02; 95% CI 2.55 to 68.99) for high-LET radiation. The ERR/Gy tended to be about five to ten times higher for high-LET versus low-LET radiation; however, the CIs largely overlapped. Results indicate no association of death from CLL (n=70) with either type of radiation. Our findings indicate an increased risk of death for specific subtypes from non-CLL in relation to chronic low-LET and high-LET radiation, but no such relation for CLL. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

PMH 9907: Long-term outcomes of a randomized phase 3 study of short-term bicalutamide hormone therapy and dose-escalated external-beam radiation therapy for localized prostate cancer.

PubMed

McPartlin, Andrew J; Glicksman, Rachel; Pintilie, Melania; Tsuji, Debbie; Mok, Gary; Bayley, Andrew; Chung, Peter; Bristow, Robert G; Gospodarowicz, Mary K; Catton, Charles N; Milosevic, Michael; Warde, Padraig R

2016-08-15

The role of hormone therapy (HT) with dose-escalated external-beam radiotherapy (DE-EBRT) in the treatment of intermediate-risk prostate cancer (IRPC) remains controversial. The authors report the long-term outcome of a phase 3 study of DE-EBRT with or without HT for patients with localized prostate cancer (LPC). From 1999 to 2006, 252 of an intended 338 patients with LPC were randomized to receive DE-EBRT with or without 5 months of neoadjuvant and concurrent bicalutamide 150 mg once daily. The study was closed early because of contemporary concerns surrounding bicalutamide. The primary outcome was biochemical failure (BF) incidence, and the secondary endpoints were overall survival (OS), local control (LC), and quality of life. The BF and OS rates were estimated using the cumulative incidence function and Kaplan-Meier methods and were compared using the Gray test and the log-rank test. Eleven patients were excluded from analysis. Characteristics were well balanced in each treatment arm. Ninety-five percent of patients had IRPC. The prescribed dose increased from 75.6 grays (Gy) in 42 fractions to 78 Gy in 39 fractions over the period. At a median follow-up of 9.1 years, 98 BFs occurred, with no significant effect of HT versus no HT on the BF rate (40% vs 47%; P = .32), the OS rate (82% vs 86%; P = .37), the LC rate (52% vs 48 %; P = .32) or quality of life, in the patients who completed the questionnaires. Dose escalation to 75.6 Gy versus >75.6 Gy reduced the BF rate by 26% (P = .004). For patients who predominantly have IRPC, the addition of HT to DE-EBRT did not significantly affect BF, OS, or LC. Bicalutamide appeared to be well tolerated. The conclusions from the study are limited by incomplete recruitment. Cancer 2016;122:2595-603. © 2016 American Cancer Society. © 2016 American Cancer Society.

Irradiation of members of the general public from radioactive caesium following the Chernobyl reactor accident: Field studies in a highly contaminated area in the Bryansk region, Russia

NASA Astrophysics Data System (ADS)

Thornberg, Charlotte

From 1990 to 1998, estimations of the effective dose due to irradiation from 137Cs and 134Cs were carried out for inhabitants in rural villages in the Bryansk region, Russia. The villages, situated about 180 km from the Chernobyl power plant received deposition of 137Cs in the range 0.9-2.7 MBq m-2 due to the accident in 1986. The body burden of 137,134Cs was estimated from measurements of the urinary concentration of caesium radionuclides, together with in vivo measurements using a portable detector. The external effective dose was estimated from measurements with thermoluminescent (TL)-dosemeters worn by the participants during one month each year. In a case study, the changes in biokinetics of 137Cs during pregnancy was investigated in a woman with an unintended intake of 137Cs via mushrooms grown in the area. During pregnancy the biological half-time of caesium was 54% of that before pregnancy. The ratio of the 137Cs concentration in breast milk (Bq L-1) to that in the mother's body (Bq kg-1) was 15% one month after the child was born. The body burden of 137Cs in the Russian individuals calculated from urine samples showed a good agreement with the body burden estimated from in vivo measurements in the same individuals. Normalisation of the caesium concentration in the urine samples by the use of potassium or creatinine excretion introduced systematic differences and a larger spread in the calculated values of the 137Cs body burden as compared with calculations without normalisation. The yearly effective dose to inhabitants in the Russian villages varied between 1.2 and 2.5 mSv as a mean for all villages between 1991 and 1998 and the internal effective dose was 30-50% of the total effective dose. The external effective dose decreased on average 15% per year, while the internal effective dose varied, depending to a great extent on the availability of mushrooms. The cumulated effective dose for a 70-year period after the accident was calculated to be 100 mSv assuming that the effective dose will decrease by only the physical decay of 137Cs (2% per year) after 1998. Individuals may receive considerably higher effective doses, up to 0.5 Sv during a life-time considering the large spread in dose values among individuals.

Extending Prednisolone Treatment Does Not Reduce Relapses in Childhood Nephrotic Syndrome

PubMed Central

Kist-van Holthe, Joana E.; van Rijswijk, Nienske; de Mos, Nienke I.; Hop, Wim C.J.; Wetzels, Jack F.M.; van der Heijden, Albert J.; Nauta, Jeroen

2012-01-01

Prolonged prednisolone treatment for the initial episode of childhood nephrotic syndrome may reduce relapse rate, but whether this results from the increased duration of treatment or a higher cumulative dose remains unclear. We conducted a randomized, double-blind, placebo-controlled trial in 69 hospitals in The Netherlands. We randomly assigned 150 children (9 months to 17 years) presenting with nephrotic syndrome to either 3 months of prednisolone followed by 3 months of placebo (n=74) or 6 months of prednisolone (n=76), and median follow-up was 47 months. Both groups received equal cumulative doses of prednisolone (approximately 3360 mg/m2). Among the 126 children who started trial medication, relapses occurred in 48 (77%) of 62 patients who received 3 months of prednisolone and 51 (80%) of 64 patients who received 6 months of prednisolone. Frequent relapses, according to international criteria, occurred with similar frequency between groups as well (45% versus 50%). In addition, there were no statistically significant differences between groups with respect to the eventual initiation of prednisolone maintenance and/or other immunosuppressive therapy (50% versus 59%), steroid dependence, or adverse effects. In conclusion, in this trial, extending initial prednisolone treatment from 3 to 6 months without increasing cumulative dose did not benefit clinical outcome in children with nephrotic syndrome. Previous findings indicating that prolonged treatment regimens reduce relapses most likely resulted from increased cumulative dose rather than the treatment duration. PMID:23274956

Decorporation Approach after Rat Lung Contamination with Plutonium: Evaluation of the Key Parameters Influencing the Efficacy of a Protracted Chelation Treatment.

PubMed

Grémy, Olivier; Coudert, Sylvie; Renault, Daniel; Miccoli, Laurent

2017-11-01

While the efficacy of a protracted zinc (Zn)- or calcium (Ca)-diethylenetriaminepentaacetic acid (DTPA) treatment in reducing transuranic body burden has already been demonstrated, questions about therapeutic variables remain. In response to this, we designed animal experiments primarily to assess both the effect of fractionation of a given dose and the effect of the frequency of dose fraction, with the same total dose. In our study, rats were contaminated intravenously with plutonium (Pu) then treated several days later with Ca-DTPA given at once or in various split-dose regimens cumulating to the same total dose and spread over several days. Similar efficacies were induced by the injection of the total dose or by splitting the dose in several smaller doses, independent of the number of doses and the dose level per injection. In a second study, rats were pulmonary contaminated, and three weeks later they received a Ca-DTPA dose 11-fold higher than the maximal daily recommended dose, administered either as a single bolus or as numerous multiple injections cumulating to the same dose, based on different injection frequency schedules. Independent of frequency schedule, the various split-dose regimens spread over weeks/months were as efficient as single delivery of the total dose in mobilizing lung plutonium, and had a therapeutic advantage for removal of retained hepatic and bone plutonium burdens. We concluded that cumulative dose level was a therapeutic variable of greater importance than the distribution of split doses for the success of a repeated treatment regimen on retained tissue plutonium. In addition, pulmonary administration of clodronate, which aims at killing alveolar macrophages and subsequently releasing their plutonium content, and which is associated with a continuous Ca-DTPA infusion regimen, suggested that the efficacy of injected Ca-DTPA in decorporating lung deposit is limited, due to its restricted penetration into alveolar macrophages and not because plutonium, as a physicochemical form, is unavailable for chelation.

Work-related lesions of the supraspinatus tendon: a case-control study.

PubMed

Seidler, Andreas; Bolm-Audorff, Ulrich; Petereit-Haack, Gabriela; Ball, Elke; Klupp, Magdalena; Krauss, Noëlle; Elsner, Gine

2011-04-01

To examine the dose-response relationship between cumulative duration of work with highly elevated arms (work above shoulder level) as well as of manual material handling and ruptures of the supraspinatus tendon in a population-based case-control study. In 14 radiologic practices, we recruited 483 male patients aged 25-65 with radiographically confirmed partial (n = 385) or total (n = 98) supraspinatus tears associated with shoulder pain. A total of 300 male control subjects were recruited. Data were gathered in a structured personal interview. To calculate cumulative exposure, the self-reported duration of lifting/carrying of heavy loads (>20 kg) as well as the duration of work with highly elevated arms was added up over the entire working life. The results of our study support a dose-response relationship between cumulative duration of work with highly elevated arms and symptomatic supraspinatus tendon tears. For a cumulative duration of >3,195 h work above shoulder level, the risk of a supraspinatus tendon rupture is elevated to 2.0 (95% CI 1.1-3.5), adjusted for age, region, lifting/carrying of heavy loads, handheld vibration, apparatus gymnastics/shot put/javelin/hammer throwing/wrestling, and tennis. The cumulative duration of carrying/lifting of heavy loads also yields a positive dose-response relation with disease (independent from work above shoulder level and from handheld vibration), with an adjusted odds ratio of 1.8 (95% CI 1.0-3.2) in the highest exposure category (>77 h). We find an increased risk for subjects exposed to handheld vibration with an adjusted OR of 3.2 (95% CI 1.7-5.9) in the highest exposure category (16 years or more in the job with exposure), but a clear dose-response relationship is lacking. This study points to a potential etiologic role of long-term cumulative effects of work with highly elevated arms and heavy lifting/carrying on shoulder tendon disorders.

No evidence found for an association between prednisone dose and FVC change in newly-treated pulmonary sarcoidosis.

PubMed

Broos, Caroline E; Poell, Linda H C; Looman, Caspar W N; In 't Veen, Johannes C C M; Grootenboers, Marco J J H; Heller, Roxane; van den Toorn, Leon M; Wapenaar, Monique; Hoogsteden, Henk C; Kool, Mirjam; Wijsenbeek, Marlies S; van den Blink, Bernt

2018-05-01

Prednisone is used as first-line therapy for pulmonary sarcoidosis. What dosing strategy has the best balance between effect and side-effects is largely unknown. We analyzed change in forced vital capacity (FVC) and weight during different prednisone doses used in daily practice for treatment naïve pulmonary sarcoidosis patients. Multilevel models were used to describe FVC and weight change over time. Correlations were calculated using linear regression models. Fifty-four patients were included. FVC changed over time (p < 0.001), with an average increase of 9.6% predicted (95% CI: 7.2 to 12.1) at 12 months. Weight changed significantly over time (p < 0.001), with an average increase of 4.3 kg (95% CI: 3.0 to 5.6) at 12 months. Although FVC and weight changed significantly over time, there was little correlation between prednisone dose and FVC change, while weight increase correlated significantly with cumulative prednisone dose at 24 months. In patients treated with a high cumulative prednisone dose, baseline FVC was on average lower (p = 0.001) compared to low dose treated patients, while no significant differences were observed in need for second/third-line therapy or number of exacerbations. A strategy leading to a low cumulative dose at 12 months was defined by rapid dose tapering to 10 mg/day within 3.5 months. These results suggest that prednisone therapy aimed at improving or preserving FVC in newly- treated pulmonary sarcoidosis can often be reduced in dose, using a treatment regimen that is characterized by early dose tapering. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inhaled corticosteroids and asthma control in adult-onset asthma: 12-year follow-up study.

PubMed

Vähätalo, Iida; Ilmarinen, Pinja; Tuomisto, Leena E; Niemelä, Onni; Kankaanranta, Hannu

2018-04-01

Prescribed inhaled corticosteroid (ICS) doses in asthma have been studied in cross-sectional settings whereas long-term follow-up studies have not been carried out. To evaluate prescribed medication longitudinally by calculating cumulative ICS doses and dose changes in a cohort of new-onset adult asthma during 12 years and in different groups of asthma control. A total of 203 patients were followed for 12 years as part of Seinäjoki Adult Asthma Study (SAAS). All asthma-related visits and prescribed medication over the study period were collected from medical records. Total cumulative ICS dose for the 12-year follow-up period was 3.4g (±SEM 0.1) per patient. Both respiratory specialists and GPs prescribed step-ups and step-downs in ICS treatment and in total 649 dose changes were noted during the follow-up (median 3(1-5) per patient). Patients with uncontrolled asthma received higher ICS doses throughout the follow-up period, and therefore, cumulative 12-year ICS dose (3.8g ± SEM 0.2) in this group was higher than that in those with partially controlled (3.4g ± SEM 0.2) or controlled disease (2.9g ± SEM 0.2) (p = 0.0001). Patients with uncontrolled asthma were also prescribed a higher number of ICS dose changes than patients with controlled disease. Despite frequent dose changes and high ICS doses during the 12-year follow-up, the level of asthma control remained poor in patients with uncontrolled asthma. This suggests that high ICS doses may not be effective enough for management of disease in patients with uncontrolled adult-onset asthma and novel targeted treatments are required. Copyright © 2018 Elsevier Ltd. All rights reserved.

Barriers to Success in Parent Training for Young Children with Developmental Delay: The Role of Cumulative Risk

ERIC Educational Resources Information Center

Bagner, Daniel M.; Graziano, Paulo A.

2013-01-01

The purpose of this study was to examine the effect of cumulative risk on dropout and treatment outcome in parent training. Participants were 44 families of young children (mean age of 49.59 months) who presented with elevated externalizing behavior problems and developmental delay or borderline developmental delay. All families were offered to…

PRESTO-II: a low-level waste environmental transport and risk assessment code

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

Fields, D.E.; Emerson, C.J.; Chester, R.O.

PRESTO-II (Prediction of Radiation Effects from Shallow Trench Operations) is a computer code designed for the evaluation of possible health effects from shallow-land and, waste-disposal trenches. The model is intended to serve as a non-site-specific screening model for assessing radionuclide transport, ensuing exposure, and health impacts to a static local population for a 1000-year period following the end of disposal operations. Human exposure scenarios considered include normal releases (including leaching and operational spillage), human intrusion, and limited site farming or reclamation. Pathways and processes of transit from the trench to an individual or population include ground-water transport, overland flow, erosion,more » surface water dilution, suspension, atmospheric transport, deposition, inhalation, external exposure, and ingestion of contaminated beef, milk, crops, and water. Both population doses and individual doses, as well as doses to the intruder and farmer, may be calculated. Cumulative health effects in terms of cancer deaths are calculated for the population over the 1000-year period using a life-table approach. Data are included for three example sites: Barnwell, South Carolina; Beatty, Nevada; and West Valley, New York. A code listing and example input for each of the three sites are included in the appendices to this report.« less

The Fukushima Health Management Survey: estimation of external doses to residents in Fukushima Prefecture

NASA Astrophysics Data System (ADS)

Ishikawa, Tetsuo; Yasumura, Seiji; Ozasa, Kotaro; Kobashi, Gen; Yasuda, Hiroshi; Miyazaki, Makoto; Akahane, Keiichi; Yonai, Shunsuke; Ohtsuru, Akira; Sakai, Akira; Sakata, Ritsu; Kamiya, Kenji; Abe, Masafumi

2015-08-01

The Fukushima Health Management Survey (including the Basic Survey for external dose estimation and four detailed surveys) was launched after the Fukushima Dai-ichi Nuclear Power Plant accident. The Basic Survey consists of a questionnaire that asks Fukushima Prefecture residents about their behavior in the first four months after the accident; and responses to the questionnaire have been returned from many residents. The individual external doses are estimated by using digitized behavior data and a computer program that included daily gamma ray dose rate maps drawn after the accident. The individual external doses of 421,394 residents for the first four months (excluding radiation workers) had a distribution as follows: 62.0%, <1 mSv 94.0%, <2 mSv 99.4%, <3 mSv. The arithmetic mean and maximum for the individual external doses were 0.8 and 25 mSv, respectively. While most dose estimation studies were based on typical scenarios of evacuation and time spent inside/outside, the Basic Survey estimated doses considering individually different personal behaviors. Thus, doses for some individuals who did not follow typical scenarios could be revealed. Even considering such extreme cases, the estimated external doses were generally low and no discernible increased incidence of radiation-related health effects is expected.

The Fukushima Health Management Survey: estimation of external doses to residents in Fukushima Prefecture

PubMed Central

Ishikawa, Tetsuo; Yasumura, Seiji; Ozasa, Kotaro; Kobashi, Gen; Yasuda, Hiroshi; Miyazaki, Makoto; Akahane, Keiichi; Yonai, Shunsuke; Ohtsuru, Akira; Sakai, Akira; Sakata, Ritsu; Kamiya, Kenji; Abe, Masafumi

2015-01-01

The Fukushima Health Management Survey (including the Basic Survey for external dose estimation and four detailed surveys) was launched after the Fukushima Dai-ichi Nuclear Power Plant accident. The Basic Survey consists of a questionnaire that asks Fukushima Prefecture residents about their behavior in the first four months after the accident; and responses to the questionnaire have been returned from many residents. The individual external doses are estimated by using digitized behavior data and a computer program that included daily gamma ray dose rate maps drawn after the accident. The individual external doses of 421,394 residents for the first four months (excluding radiation workers) had a distribution as follows: 62.0%, <1 mSv; 94.0%, <2 mSv; 99.4%, <3 mSv. The arithmetic mean and maximum for the individual external doses were 0.8 and 25 mSv, respectively. While most dose estimation studies were based on typical scenarios of evacuation and time spent inside/outside, the Basic Survey estimated doses considering individually different personal behaviors. Thus, doses for some individuals who did not follow typical scenarios could be revealed. Even considering such extreme cases, the estimated external doses were generally low and no discernible increased incidence of radiation-related health effects is expected. PMID:26239643

Long-Term Results of a Phase II Trial of Ultrasound-Guided Radioactive Implantation of the Prostate for Definitive Management of Localized Adenocarcinoma of the Prostate (RTOG 98-05)

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

Lawton, Colleen A., E-mail: clawton@mcw.edu; Hunt, Daniel; Lee, W. Robert

2011-09-01

Purpose: To evaluate the long-term effectiveness of transrectal ultrasound-guided permanent radioactive I{sup 125} implantation of the prostate for organ confined adenocarcinoma of the prostate compared with historical data of prostatectomy and external beam radiotherapy within a cooperative group setting. Methods and Materials: Patients accrued to this study had histologically confirmed, locally confined adenocarcinoma of the prostate clinical stage T1b, T1c, or T2a; no nodal or metastatic disease; prostate-specific antigen level of {<=}10 ng/ml; and a Gleason score of {<=}6. All patients underwent transrectal ultrasound-guided radioactive I{sup 125} seed implantation into the prostate. The prescribed dose was 145 Gy to themore » prostate planning target volume. Results: A total of 101 patients from 27 institutions were accrued to this protocol; by design, no single institution accrued more than 8 patients. There were 94 eligible patients. The median follow up was 8.1 years (range, 0.1-9.2 years). After 8 years, 8 patients had protocol-defined biochemical (prostate-specific antigen) failure (cumulative incidence, 8.0%); 5 patients had local failure (cumulative incidence, 5.5%); and 1 patient had distant failure (cumulative incidence, 1.1%; this patient also had biochemical failure and died of causes not related to prostate cancer). The 8-year overall survival rate was 88%. At last follow-up, no patient had died of prostate cancer or related toxicities. Three patients had maximum late toxicities of Grade 3, all of which were genitourinary. No Grade 4 or 5 toxicities were observed. Conclusions: The long-term results of this clinical trial have demonstrated that this kind of trial can be successfully completed through the RTOG and that results in terms of biochemical failure and toxicity compare very favorably with other brachytherapy published series as well as surgical and external beam radiotherapy series. In addition, the prospective, multicenter design highlights the probable generalizability of the outcomes.« less

The Association Between the Use of Zolpidem and the Risk of Alzheimer's Disease Among Older People.

PubMed

Cheng, Hui-Ting; Lin, Fang-Ju; Erickson, Steven R; Hong, Jin-Liern; Wu, Chung-Hsuen

2017-11-01

To evaluate the association between zolpidem use and the risk of Alzheimer's disease among older people. A retrospective cohort study using data from 2001 to 2011 from the National Health Insurance Research Database. Taiwan. A total of 6,922 patients aged 65 years or older enrolled from January 2002 to December 2004 (the enrollment period). Zolpidem users were identified as patients who used zolpidem during the enrollment period. The index date was the date of the first zolpidem prescription. Dosage of zolpidem use was defined using cumulative defined daily dose (cDDD) based on the cumulative dosage that patients took within one year after the index date (grouped as: less than 28, 28-90, 91-180, and more than 180 cDDD). The occurrence of Alzheimer's disease was defined as the time period from the end of one year after the index date to the date of the Alzheimer's disease diagnosis. The propensity score was used to adjust the measured confounders of Alzheimer's disease. Cox proportional hazards models were used to evaluate the association between zolpidem use and the incidence of Alzheimer's disease. Zolpidem users with a high cumulative dose (>180 cDDD) in the first year after initiation had a significantly greater risk of Alzheimer's disease than non-zolpidem users (HR = 2.97, 95% CI = 1.61-5.49) and low cumulative dose (<28 cDDD) users (HR = 4.18, 95% CI = 1.77-9.86). We found the use of a high cumulative dose of zolpidem was associated with an increased risk of Alzheimer's disease among older people living in Taiwan. It is advised to use caution when considering long-term use of zolpidem in older patients. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Clinical research on liver reserve function by 13C-phenylalanine breath test in aged patients with chronic liver diseases

PubMed Central

2010-01-01

Background The objective of this study was to investigate whether the 13C-phenylalanine breath test could be useful for the evaluation of hepatic function in elderly volunteers and patients with chronic hepatitis B and liver cirrhosis. Methods L-[1-13C] phenylalanine was administered orally at a dose of 100 mg to 55 elderly patients with liver cirrhosis, 30 patients with chronic hepatitis B and 38 elderly healthy subjects. The breath test was performed at 8 different time points (0, 10, 20, 30, 45, 60, 90, 120 min) to obtain the values of Delta over baseline, percentage 13CO2 exhalation rate and cumulative excretion (Cum). The relationships of the cumulative excretion with the 13C-%dose/h and blood biochemical parameters were investigated. Results The 13C-%dose/h at 20 min and 30 min combined with the cumulative excretion at 60 min and 120 min correlated with hepatic function tests, serum albumin, hemoglobin, platelet and Child-Pugh score. Prothrombin time, total and direct bilirubin were significantly increased, while serum albumin, hemoglobin and platelet, the cumulative excretion at 60 min and 120 min values decreased by degrees of intensity of the disease in Child-Pugh A, B, and C patients (P < 0.01). Conclusions The 13C-phenylalanine breath test can be used as a non-invasive assay to evaluate hepatic function in elderly patients with liver cirrhosis. The 13C-%dose/h at 20 min, at 30 min and cumulative excretion at 60 min may be the key value for determination at a single time-point. 13C-phenylalanine breath test is safe and helpful in distinguishing different stages of hepatic dysfunction for elderly cirrhosis patients. PMID:20459849

Real time chemical exposure and risk monitor

DOEpatents

Thrall, Karla D.; Kenny, Donald V.; Endres, George W. R.; Sisk, Daniel R.

1997-01-01

The apparatus of the present invention is a combination of a breath interface and an external exposure dosimeter interface to a chemical analysis device, all controlled by an electronic processor for quantitatively analyzing chemical analysis data from both the breath interface and the external exposure dosimeter for determining internal tissue dose. The method of the present invention is a combination of steps of measuring an external dose, measuring breath content, then analyzing the external dose and breath content and determining internal tissue dose.

Real time chemical exposure and risk monitor

DOEpatents

Thrall, K.D.; Kenny, D.V.; Endres, G.W.R.; Sisk, D.R.

1997-07-08

The apparatus of the present invention is a combination of a breath interface and an external exposure dosimeter interface to a chemical analysis device, all controlled by an electronic processor for quantitatively analyzing chemical analysis data from both the breath interface and the external exposure dosimeter for determining internal tissue dose. The method of the present invention is a combination of steps of measuring an external dose, measuring breath content, then analyzing the external dose and breath content and determining internal tissue dose. 7 figs.

Lack of developmental and reproductive toxicity of 2,3,3',4,4'-pentachlorobiphenyl (PCB-105) in Ring-Necked Pheasants

USGS Publications Warehouse

Hornung, M.W.; Miller, L.; Goodman, B.; Melancon, M.J.; Peterson, R.E.

1998-01-01

Mono-ortho PCBs are global contaminants of wildlife with the potential to produce toxicity by an aryl hydrocarbon receptor (AhR)-mediated mechanism. To determine the potency of 2,3,3',4,4'pentachlorobiphenyl (PCB-105) for producing reproductive and developmental toxicity, adult ring-necked pheasant hens (Phasianus colchicus) were orally dosed with 0, 0.06, 0.6 or 6 mg PCB105/kg hen/week for 10 weeks to achieve cumulative doses of 0, 0.6, 6, or 60 mg PCB -105/hen after which hens were bred with untreated roosters once per week for 8 weeks. Except at week 6 of the egglaying period when cumulative egg production in the 6mg PCB 105/hen group was greater than controls, fertilized egg production was not significantly different between treatment groups. Embryo mortality and chick mortality were not significantly different between treatment groups. Total body and heart weights of all chicks 1 day posthatch (dph) were not different between groups, however liver weights of chicks from the 60mg/kg treatment groups were greater than controls at 1 dph. The first chick to hatch from each hen was reared to 21 dph and among these birds the total body, liver and heart weights were not different between groups. There were no dose-related malformations of the beak or limbs, and no signs of subcutaneous edema, ascites, or pericardial edema in chicks at 1 or 21 dph. Hepatic microsomal monooxygenase activities [ethoxyresorufin-O-dealkylase (EROD), benzyloxyresorufin-O-dealkylase (BROD), and methyloxyresorufin-O-dealkylase (MROD)] were significantly elevated in chicks at 1 dph from hens given a cumulative PCB105 dose of 6 mg/kg and in chicks at 21 dph from hens given a cumulative PCB dose of 60 mg/kg. These results indicate that a cumulative PCB-105 dose up to 60 mg/kg hen does not decrease the production of fertilized eggs or increase embryo or chick mortality in ring-necked pheasants, but does increase chick hepatic monooxygenase activity.

The Effect of Total Cumulative Dose, Number of Treatment Cycles, Interval between Injections, and Length of Treatment on the Frequency of Occurrence of Antibodies to Botulinum Toxin Type A in the Treatment of Muscle Spasticity

ERIC Educational Resources Information Center

Bakheit, Abdel Magid O.; Liptrot, Anthea; Newton, Rachel; Pickett, Andrew M.

2012-01-01

A large cumulative dose of botulinum toxin type A (BoNT-A), frequent injections, a short interval between treatment cycles, and a long duration of treatment have all been suggested, but not confirmed, to be associated with a high incidence of neutralizing antibodies to the neurotoxin. The aim of this study was to investigate whether these…

Development of doxorubicin-induced chronic cardiotoxicity in the B6C3F{sub 1} mouse model

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

Desai, Varsha G., E-mail: varsha.desai@fda.hhs.gov; Herman, Eugene H.; Moland, Carrie L.

2013-01-01

Serum levels of cardiac troponins serve as biomarkers of myocardial injury. However, troponins are released into the serum only after damage to cardiac tissue has occurred. Here, we report development of a mouse model of doxorubicin (DOX)-induced chronic cardiotoxicity to aid in the identification of predictive biomarkers of early events of cardiac tissue injury. Male B6C3F{sub 1} mice were administered intravenous DOX at 3 mg/kg body weight, or an equivalent volume of saline, once a week for 4, 6, 8, 10, 12, and 14 weeks, resulting in cumulative DOX doses of 12, 18, 24, 30, 36, and 42 mg/kg, respectively.more » Mice were sacrificed a week following the last dose. A significant reduction in body weight gain was observed in mice following exposure to a weekly DOX dose for 1 week and longer compared to saline-treated controls. DOX treatment also resulted in declines in red blood cell count, hemoglobin level, and hematocrit compared to saline-treated controls after the 2nd weekly dose until the 8th and 9th doses, followed by a modest recovery. All DOX-treated mice had significant elevations in cardiac troponin T concentrations in plasma compared to saline-treated controls, indicating cardiac tissue injury. Also, a dose-related increase in the severity of cardiac lesions was seen in mice exposed to 24 mg/kg DOX and higher cumulative doses. Mice treated with cumulative DOX doses of 30 mg/kg and higher showed a significant decline in heart rate, suggesting drug-induced cardiac dysfunction. Altogether, these findings demonstrate the development of DOX-induced chronic cardiotoxicity in B6C3F{sub 1} mice. -- Highlights: ► 24 mg/kg was a cumulative cardiotoxic dose of doxorubicin in male B6C3F{sub 1} mice. ► Doxorubicin-induced hematological toxicity was in association with splenomegaly. ► Doxorubicin induced severe testicular toxicity in B6C3F{sub 1} male mice.« less

Early transcriptional changes in cardiac mitochondria during chronic doxorubicin exposure and mitigation by dexrazoxane in mice

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

Vijay, Vikrant; Moland, Carrie L.; Han, Tao

Identification of early biomarkers of cardiotoxicity could help initiate means to ameliorate the cardiotoxic actions of clinically useful drugs such as doxorubicin (DOX). Since DOX has been shown to target mitochondria, transcriptional levels of mitochondria-related genes were evaluated to identify early candidate biomarkers in hearts of male B6C3F{sub 1} mice given a weekly intravenous dose of 3 mg/kg DOX or saline (SAL) for 2, 3, 4, 6, or 8 weeks (6, 9, 12, 18, or 24 mg/kg cumulative DOX doses, respectively). Also, a group of mice was pretreated (intraperitoneally) with the cardio-protectant, dexrazoxane (DXZ; 60 mg/kg) 30 min before eachmore » weekly dose of DOX or SAL. At necropsy a week after the last dose, increased plasma concentrations of cardiac troponin T (cTnT) were detected at 18 and 24 mg/kg cumulative DOX doses, whereas myocardial alterations were observed only at the 24 mg/kg dose. Of 1019 genes interrogated, 185, 109, 140, 184, and 451 genes were differentially expressed at 6, 9, 12, 18, and 24 mg/kg cumulative DOX doses, respectively, compared to concurrent SAL-treated controls. Of these, expression of 61 genes associated with energy metabolism and apoptosis was significantly altered before and after occurrence of myocardial injury, suggesting these as early genomics markers of cardiotoxicity. Much of these DOX-induced transcriptional changes were attenuated by pretreatment of mice with DXZ. Also, DXZ treatment significantly reduced plasma cTnT concentration and completely ameliorated cardiac alterations induced by 24 mg/kg cumulative DOX. This information on early transcriptional changes during DOX treatment may be useful in designing cardioprotective strategies targeting mitochondria. - Highlights: • Altered mitochondria-related gene expression before heart injury by doxorubicin • Dexrazoxane mitigated doxorubicin-induced early expression changes in mitochondria. • Dexrazoxane completely ameliorated doxorubicin-induced pathology in mouse heart.« less

Effect of co-medication on the pharmacokinetic parameters of phenobarbital in asphyxiated newborns.

PubMed

Šíma, M; Pokorná, P; Hronová, K; Slanař, O

2015-01-01

Phenobarbital is an anticonvulsive drug widely used in newborns with hypoxic-ischemic encephalopathy. The objective of our study was to describe possible effect of frequently co-administered medications (dopamine, dobutamine, norepinephrine, furosemide, phenytoin, and analgesics) on the phenobarbital pharmacokinetics in full term newborns with hypoxic-ischemic encephalopathy. Phenobarbital pharmacokinetic parameters (standardized intravenous loading dose was 10-20 mg/kg, maintenance dose 2-6 mg/kg/day) were computed using non-compartmental analysis. Co-medication was evaluated throughout the whole treatment period up to 5 days. Volume of distribution, clearance, and half-life median values (95 % CI) for phenobarbital in the whole study population (n=37) were 0.48 (0.41-0.56) l/kg, 0.0034 (0.0028-0.0040) l/h/kg, and 93.7 (88.1-99.2) h, respectively. Phenobarbital pharmacokinetic parameters were not significantly affected by vasoactive drugs (dopamine, dobutamine, and norepinephrine), furosemide, phenytoin, or analgesics. Furthermore, no dose-dependent alteration of phenobarbital pharmacokinetic parameters was noted for vasoactive medication at doses equivalent to cumulative vasoactive-inotropic score (area under the curve in a plot of vasoactive-inotropic score against time) 143.2-8473.6, furosemide at cumulative doses of 0.2-42.9 mg/kg, or phenytoin at cumulative doses of 10.3-46.2 mg/kg. Phenobarbital pharmacokinetics was not affected by investigated co-administered drugs used in newborns with hypoxic-ischemic encephalopathy in real clinical settings.

Characterization of efficacy and toxicity after high-dose pelvic reirradiation with palliative intent for genitourinary second malignant neoplasms or local recurrences after full-dose radiation therapy in the pelvis: A high-volume cancer center experience.

PubMed

Kamran, Sophia C; Harshman, Lauren C; Bhagwat, Mandar S; Muralidhar, Vinayak; Nguyen, Paul L; Martin, Neil E; La Follette, Stephanie; Faso, Sarah; Viswanathan, Akila N; Efstathiou, Jason A; Beard, Clair J

2017-01-01

The use of large-field external beam reirradiation (re-RT) after pelvic radiation therapy (RT) for genitourinary (GU) cancers has not been reported. We report the results of such treatment in patients with either symptomatic GU second malignant neoplasms or locally recurrent pelvic tumors after initial RT for whom surgery or further systemic therapy was not an option. The records of 28 consecutive patients with advanced, bulky GU malignancies treated with high-dose, large-field re-RT with palliative intent between 2008 and 2014 were retrospectively reviewed. Descriptive outcome analyses focused on toxicities and symptom control, and responses were evaluated by 2 independent observers. Twenty-seven male patients (96%) were included. Median initial external beam RT dose was 64 Gy (range, 30-75.6 Gy). The median time between initial RT and re-RT was 9.5 years (range, 0.2-32 years). At the time of re-RT, there were 16 local recurrences and 12 second malignant neoplasms together comprising 16 bladder, 10 prostate, 1 ureteral, and 1 penile cancer. Indications for re-RT were pain and bleeding/hemorrhage. The median equivalent sphere diameter planning target volume for re-RT was 8.6 cm (range, 4.7-16.3 cm). Given the severity of the symptoms and the bulk of the disease at the time of re-RT, a higher dose of RT was administered. The median re-RT dose was 50 Gy (range, 27.5-66 Gy). For patients who received <60 Gy, hypofractionation of 250 cGy was used. The median cumulative dose was 113.9 Gy (range, 81.5-132.8 Gy). Re-RT was well tolerated with no Radiation Therapy Oncology Group grade 3-4 toxicities. Twenty-four patients (92%) had complete resolution of symptoms, and relief was durable in 67% of patients. The median overall survival was 5.8 months (range, 0.3-38.9 months). Of those patients who are still alive, 100% remain free of initial symptoms. This small series suggests that aggressive re-RT of inoperable and symptomatic GU malignancies that is undertaken with meticulous treatment planning is well tolerated and provides excellent, durable relief without undue short-term toxicity. Validation in a larger prospective cohort is required.

Acute and Cumulative Effects of Unmodified 50-nm Nano-ZnO on Mice.

PubMed

Kong, Tao; Zhang, Shu-Hui; Zhang, Ji-Liang; Hao, Xue-Qin; Yang, Fan; Zhang, Cai; Yang, Zi-Jun; Zhang, Meng-Yu; Wang, Jie

2018-01-02

Nanometer zinc oxide (nano-ZnO) is widely used in diverse industrial and agricultural fields. Due to the extensive contact humans have with these particles, it is crucial to understand the potential effects that nano-ZnO have on human health. Currently, information related to the toxicity and mechanisms of nano-ZnO is limited. The aim of the present study was to investigate acute and cumulative toxic effects of 50-nm unmodified ZnO in mice. This investigation will seek to establish median lethal dose (LD50), a cumulative coefficient, and target organs. The acute and cumulative toxicity was investigated by Karber's method and via a dose-increasing method, respectively. During the experiment, clinical signs, mortality, body weights, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. The LD50 was 5177-mg/kg·bw; the 95% confidence limits for the LD50 were 5116-5238-mg/kg·bw. It could be concluded that the liver, kidney, lung, and gastrointestinal tract were target organs for the 50-nm nano-ZnO acute oral treatment. The cumulative coefficient (K) was 1.9 which indicated that the cumulative toxicity was apparent. The results also indicated that the liver, kidney, lung, and pancrea were target organs for 50-nm nano-ZnO cumulative oral exposure and might be target organs for subchronic and chronic toxicity of oral administered 50-nm ZnO.

Direct measurement of a patient's entrance skin dose during pediatric cardiac catheterization

PubMed Central

Sun, Lue; Mizuno, Yusuke; Iwamoto, Mari; Goto, Takahisa; Koguchi, Yasuhiro; Miyamoto, Yuka; Tsuboi, Koji; Chida, Koichi; Moritake, Takashi

2014-01-01

Children with complex congenital heart diseases often require repeated cardiac catheterization; however, children are more radiosensitive than adults. Therefore, radiation-induced carcinogenesis is an important consideration for children who undergo those procedures. We measured entrance skin doses (ESDs) using radio-photoluminescence dosimeter (RPLD) chips during cardiac catheterization for 15 pediatric patients (median age, 1.92 years; males, n = 9; females, n = 6) with cardiac diseases. Four RPLD chips were placed on the patient's posterior and right side of the chest. Correlations between maximum ESD and dose–area products (DAP), total number of frames, total fluoroscopic time, number of cine runs, cumulative dose at the interventional reference point (IRP), body weight, chest thickness, and height were analyzed. The maximum ESD was 80 ± 59 (mean ± standard deviation) mGy. Maximum ESD closely correlated with both DAP (r = 0.78) and cumulative dose at the IRP (r = 0.82). Maximum ESD for coiling and ballooning tended to be higher than that for ablation, balloon atrial septostomy, and diagnostic procedures. In conclusion, we directly measured ESD using RPLD chips and found that maximum ESD could be estimated in real-time using angiographic parameters, such as DAP and cumulative dose at the IRP. Children requiring repeated catheterizations would be exposed to high radiation levels throughout their lives, although treatment influences radiation dose. Therefore, the radiation dose associated with individual cardiac catheterizations should be analyzed, and the effects of radiation throughout the lives of such patients should be followed. PMID:24968708

Assessment of radiation exposure from cesium-137 contaminated roads for epidemiological studies in Seoul, Korea

PubMed Central

Lee, Yun-Keun; Ju, Young-Su; Lee, Won Jin; Hwang, Seung Sik; Yim, Sang-Hyuk; Yoo, Sang-Chul; Lee, Jieon; Choi, Kyung-Hwa; Burm, Eunae; Ha, Mina

2015-01-01

Objectives We aimed to assess the radiation exposure for epidemiologic investigation in residents exposed to radiation from roads that were accidentally found to be contaminated with radioactive cesium-137 (137Cs) in Seoul. Methods Using information regarding the frequency and duration of passing via the 137Cs contaminated roads or residing/working near the roads from the questionnaires that were obtained from 8875 residents and the measured radiation doses reported by the Nuclear Safety and Security Commission, we calculated the total cumulative dose of radiation exposure for each person. Results Sixty-three percent of the residents who responded to the questionnaire were considered as ever-exposed and 1% of them had a total cumulative dose of more than 10 mSv. The mean (minimum, maximum) duration of radiation exposure was 4.75 years (0.08, 11.98) and the geometric mean (minimum, maximum) of the total cumulative dose was 0.049 mSv (<0.001, 35.35) in the exposed. Conclusions An individual exposure assessment was performed for an epidemiological study to estimate the health risk among residents living in the vicinity of 137Cs contaminated roads. The average exposure dose in the exposed people was less than 5% of the current guideline. PMID:26184047

LEUKEMIA, LYMPHOMA AND MULTIPLE MYELOMA MORTALITY (1950–1999) AND INCIDENCE (1969–1999) IN THE ELDORADO URANIUM WORKERS COHORT

PubMed Central

Zablotska, Lydia B.; Lane, Rachel S.D.; Frost, Stanley E.; Thompson, Patsy A.

2014-01-01

Uranium workers are chronically exposed to low levels of radon decay products (RDP) and gamma (γ) radiation. Risks of leukemia from acute and high doses of γ-radiation are well-characterized, but risks from lower doses and dose-rates and from RDP exposures are controversial. Few studies have evaluated risks of other hematologic cancers in uranium workers. The purpose of this study was to analyze radiation-related risks of hematologic cancers in the cohort of Eldorado uranium miners and processors first employed in 1932–1980 in relation to cumulative RDP exposures and γ-ray doses. The average cumulative RDP exposure was 100.2 working level months and the average cumulative whole-body γ-radiation dose was 52.2 millisievert. We identified 101 deaths and 160 cases of hematologic cancers in the cohort. Overall, male workers had lower mortality and cancer incidence rates for all outcomes compared with the general Canadian male population, a likely healthy worker effect. No statistically significant association between RDP exposure or γ-ray doses, or a combination of both, and mortality or incidence of any hematologic cancer was found. We observed consistent but non-statistically significant increases in risks of chronic lymphocytic leukemia (CLL) and Hodgkin lymphoma (HL) incidence and non-Hodgkin lymphoma (NHL) mortality with increasing γ-ray doses. These findings are consistent with recent studies of increased risks of CLL and NHL incidence after γ-radiation exposure. Further research is necessary to understand risks of other hematologic cancers from low-dose exposures to γ-radiation. PMID:24583244

External doses of residents near Semipalatinsk nuclear test site.

PubMed

Takada, J; Hoshi, M; Nagatomo, T; Yamamoto, M; Endo, S; Takatsuji, T; Yoshikawa, I; Gusev, B I; Sakerbaev, A K; Tchaijunusova, N J

1999-12-01

Accumulated external radiation doses of residents near the Semipalatinsk nuclear test site of the former USSR are presented as a results of study by the thermoluminescence technique for bricks sampled at several settlements in 1995 and 1996. The external doses that we evaluated from exposed bricks were up to about 100 cGy for resident. The external doses at several points in the center of Semipalatinsk City ranged from a background level to 60 cGy, which was remarkably high compared with the previously reported values based on military data.

Analysis and evaluation for consumer goods containing NORM in Korea.

PubMed

Jang, Mee; Chung, Kun Ho; Lim, Jong Myoung; Ji, Young Yong; Kim, Chang Jong; Kang, Mun Ja

2017-08-01

We analyzed the consumer goods containing NORM by ICP-MS and evaluated the external dose. To evaluate the external dose, we assumed the small room model as irradiation scenario and calculated the specific effective dose rate using MCNPX code. The external doses for twenty goods are less than 1 mSv considering the specific effective dose rates and usage quantities. However, some of them have relatively high dose and the activity concentration limits are necessary as a screening tool. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of childhood thyroid cancer prevalence among 3 areas based on external radiation dose after the Fukushima Daiichi nuclear power plant accident

PubMed Central

Ohira, Tetsuya; Takahashi, Hideto; Yasumura, Seiji; Ohtsuru, Akira; Midorikawa, Sanae; Suzuki, Satoru; Fukushima, Toshihiko; Shimura, Hiroki; Ishikawa, Tetsuo; Sakai, Akira; Yamashita, Shunichi; Tanigawa, Koichi; Ohto, Hitoshi; Abe, Masafumi; Suzuki, Shinichi

2016-01-01

Abstract The 2011 Great East Japan Earthquake led to a subsequent nuclear accident at the Fukushima Daiichi Nuclear Power Plant. In its wake, we sought to examine the association between external radiation dose and thyroid cancer in Fukushima Prefecture. We applied a cross-sectional study design with 300,476 participants aged 18 years and younger who underwent thyroid examinations between October 2011 and June 2015. Areas within Fukushima Prefecture were divided into three groups based on individual external doses (≥1% of 5 mSv, <99% of 1 mSv/y, and the other). The odds ratios (ORs) and 95% confidence intervals of thyroid cancer for all areas, with the lowest dose area as reference, were calculated using logistic regression models adjusted for age and sex. Furthermore, the ORs of thyroid cancer for individual external doses of 1 mSv or more and 2 mSv or more, with the external dose less than 1 mSv as reference, were calculated. Prevalence of thyroid cancer for the location groups were 48/100,000 for the highest dose area, 36/100,000 for the middle dose area, and 41/100,000 for the lowest dose area. Compared with the lowest dose area, age-, and sex-adjusted ORs (95% confidence intervals) for the highest-dose and middle-dose areas were 1.49 (0.36–6.23) and 1.00 (0.67–1.50), respectively. The duration between accident and thyroid examination was not associated with thyroid cancer prevalence. There were no significant associations between individual external doses and prevalence of thyroid cancer. External radiation dose was not associated with thyroid cancer prevalence among Fukushima children within the first 4 years after the nuclear accident. PMID:27583855

Comparison of childhood thyroid cancer prevalence among 3 areas based on external radiation dose after the Fukushima Daiichi nuclear power plant accident: The Fukushima health management survey.

PubMed

Ohira, Tetsuya; Takahashi, Hideto; Yasumura, Seiji; Ohtsuru, Akira; Midorikawa, Sanae; Suzuki, Satoru; Fukushima, Toshihiko; Shimura, Hiroki; Ishikawa, Tetsuo; Sakai, Akira; Yamashita, Shunichi; Tanigawa, Koichi; Ohto, Hitoshi; Abe, Masafumi; Suzuki, Shinichi

2016-08-01

The 2011 Great East Japan Earthquake led to a subsequent nuclear accident at the Fukushima Daiichi Nuclear Power Plant. In its wake, we sought to examine the association between external radiation dose and thyroid cancer in Fukushima Prefecture. We applied a cross-sectional study design with 300,476 participants aged 18 years and younger who underwent thyroid examinations between October 2011 and June 2015. Areas within Fukushima Prefecture were divided into three groups based on individual external doses (≥1% of 5 mSv, <99% of 1 mSv/y, and the other). The odds ratios (ORs) and 95% confidence intervals of thyroid cancer for all areas, with the lowest dose area as reference, were calculated using logistic regression models adjusted for age and sex. Furthermore, the ORs of thyroid cancer for individual external doses of 1 mSv or more and 2 mSv or more, with the external dose less than 1 mSv as reference, were calculated. Prevalence of thyroid cancer for the location groups were 48/100,000 for the highest dose area, 36/100,000 for the middle dose area, and 41/100,000 for the lowest dose area. Compared with the lowest dose area, age-, and sex-adjusted ORs (95% confidence intervals) for the highest-dose and middle-dose areas were 1.49 (0.36-6.23) and 1.00 (0.67-1.50), respectively. The duration between accident and thyroid examination was not associated with thyroid cancer prevalence. There were no significant associations between individual external doses and prevalence of thyroid cancer. External radiation dose was not associated with thyroid cancer prevalence among Fukushima children within the first 4 years after the nuclear accident.

Rapid Hymenoptera venom immunotherapy: comparative safety of three protocols.

PubMed

Birnbaum, J; Charpin, D; Vervloet, D

1993-03-01

We compared 284 sting-allergic patients treated with either a 4 day (group 1), 6 hr (group 2) or 210 min (group 3) rapid venom immunotherapy (RVIT) protocol using honey bee (HB) or yellow jacket (YJ) venom at cumulative doses of 527.6 micrograms, 226.6 micrograms and 101.1 micrograms respectively. The 4 day protocol involved four times as many injections as the 210 min protocol and twice as many as the 6 hr protocol. Desensitization was conducted in a hospital providing full emergency resuscitation facilities. In group 1, 1 x 100 micrograms boosters were given on days 7, 10, 15 and 45 and, in groups 2 and 3, 2 x 50 micrograms boosters were given on day 15 and 1 x 100 micrograms on day 45. The patients in the three groups were comparable with regard to clinical characteristics and immunological reactivity determined by skin tests. All patients had large local reactions. Systemic reactions (SR) occurred in 28.2% of patients in group 1, 28.6% in group 2 and 6.9% in group 3. The mean total cumulative venom dose (s.e.m.) for occurrence of SR was 123.75 (+/- 24.2) in group 1, 183.27 (+/- 28.5) in group 2, and 36.43 (+/- 9.3) in group 3. HB led to more systemic reactions than YJ venom. The rate of SR decreased when the cumulative venom dose was reduced during RVIT. The median dose was 137.6 micrograms in group 1, 226.6 micrograms in group 2, and 21.1 micrograms in group 3. No systemic reactions were observed after the booster injections. The results of this study suggest that short RVIT protocols with low cumulative doses carry a lesser risk of SR.

A randomized, double-blinded, placebo-controlled oral challenge study to evaluate the allergenicity of commercial, food-grade fish gelatin.

PubMed

Hansen, Tine K; Poulsen, Lars K; Stahl Skov, Per; Hefle, Susan L; Hlywka, Jason J; Taylor, Steve L; Bindslev-Jensen, Ulla; Bindslev-Jensen, Carsten

2004-12-01

Recent interest in the labeling of foods and food proteins derived from allergenic sources necessitates determination of the potential allergenicity of such food ingredients. Fish gelatin is extracted from the skin of fish species known to elicit allergic reactions in sensitized individuals. To determine the allergenicity of fish gelatin by double-blinded, placebo-controlled food challenges (DBPCFC) in clinically fish-allergic individuals. Thirty fish-allergic patients diagnosed according to the EAACI Guidelines were included (age 9-50 years). Skin prick tests (SPT) and Histamine Release tests (HR) were performed with fish gelatin and codfish, and codfish-specific IgE was measured. All patients underwent DBPCFC with a cumulative dose of 14.61 g fish gelatin. In all 30 patients SPT, HR, and specific IgE to codfish were positive. SPT and HR with fish gelatin were positive in 3/30 and 7/30, respectively. One patient showed mild reaction to placebo and no reaction to the active challenge. Two patients reported mild subjective reactions to active challenge. Upon re-challenge one of them described subjective symptoms again to the active challenge (7.61 g cumulated dose of fish gelatin) with no reaction to placebo, while the other experienced very mild subjective symptoms to placebo and nothing to the active. The proportion of truly sensitive patients was estimated to 0.03 in the total study group. None of 30 fish allergic patients reacted adversely to the ingestion of 3.61 g cumulative dose of fish gelatin. In this study fish gelatin presents no risk to fish-allergic patients at the doses typically used. Statistically, these results indicate that there is 95% certainty that 90% of fish-allergic consumers will not react to ingestion of a 3.61 g cumulative dose of fish gelatin.

DOSE-RESPONSE MODELING FOR THE ASSESSMENT OF CUMULATIVE RISK DUE TO EXPOSURE TO N-METHYL CARBAMATE PESTICIDES

EPA Science Inventory

The US EPAs N-Methyl Carbamate Cumulative Risk Assessment (NMCRA) assesses the effect on acetylcholine esterase (AChE) activity of exposure to 10 N-methyl carbamate (NMC) pesticides through dietary, drinking water, and residential exposures.

CUMULATIVE RISK ASSESSMENT FOR QUANTITATIVE RESPONSE DATA

EPA Science Inventory

The Relative Potency Factor approach (RPF) is used to normalize and combine different toxic potencies among a group of chemicals selected for cumulative risk assessment. The RPF method assumes that the slopes of the dose-response functions are all equal; but this method depends o...

Cumulative organophosphate pesticide exposure and risk assessment among pregnant women living in an agricultural community: a case study from the CHAMACOS cohort.

PubMed Central

Castorina, Rosemary; Bradman, Asa; McKone, Thomas E; Barr, Dana B; Harnly, Martha E; Eskenazi, Brenda

2003-01-01

Approximately 230,000 kg of organophosphate (OP) pesticides are applied annually in California's Salinas Valley. These activities have raised concerns about exposures to area residents. We collected three spot urine samples from pregnant women (between 1999 and 2001) enrolled in CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas), a longitudinal birth cohort study, and analyzed them for six dialkyl phosphate metabolites. We used urine from 446 pregnant women to estimate OP pesticide doses with two deterministic steady-state modeling methods: method 1, which assumed the metabolites were attributable entirely to a single diethyl or dimethyl OP pesticide; and method 2, which adapted U.S. Environmental Protection Agency (U.S. EPA) draft guidelines for cumulative risk assessment to estimate dose from a mixture of OP pesticides that share a common mechanism of toxicity. We used pesticide use reporting data for the Salinas Valley to approximate the mixture to which the women were exposed. Based on average OP pesticide dose estimates that assumed exposure to a single OP pesticide (method 1), between 0% and 36.1% of study participants' doses failed to attain a margin of exposure (MOE) of 100 relative to the U.S. EPA oral benchmark dose(10) (BMD(10)), depending on the assumption made about the parent compound. These BMD(10) values are doses expected to produce a 10% reduction in brain cholinesterase activity compared with background response in rats. Given the participants' average cumulative OP pesticide dose estimates (method 2) and regardless of the index chemical selected, we found that 14.8% of the doses failed to attain an MOE of 100 relative to the BMD(10) of the selected index. An uncertainty analysis of the pesticide mixture parameter, which is extrapolated from pesticide application data for the study area and not directly quantified for each individual, suggests that this point estimate could range from 1 to 34%. In future analyses, we will use pesticide-specific urinary metabolites, when available, to evaluate cumulative OP pesticide exposures. PMID:14527844

USING DOSE ADDITION TO ESTIMATE CUMULATIVE RISKS FROM EXPOSURES TO MULTIPLE CHEMICALS

EPA Science Inventory

The Food Quality Protection Act (FQPA) of 1996 requires the EPA to consider the cumulative risk from exposure to multiple chemicals that have a common mechanism of toxicity. Three methods, hazard index (HI), point-of-departure index (PODI), and toxicity equivalence factor (TEF), ...

EFFECTS-BASED CUMULATIVE RISK ASSESSMENT IN A LOW-INCOME URBAN COMMUNITY NEAR A SUPERFUND SITE

EPA Science Inventory

We will introduce into the cumulative risk assessment framework novel methods for non-cancer risk assessment, techniques for dose-response modeling that extend insights from chemical mixtures frameworks to non-chemical stressors, multilevel statistical methods used to address ...

An Integrated Approach to Segmentation and Nonrigid Registration for Application in Image-Guided Pelvic Radiotherapy

PubMed Central

Lu, Chao; Chelikani, Sudhakar; Papademetris, Xenophon; Knisely, Jonathan P.; Milosevic, Michael F.; Chen, Zhe; Jaffray, David A.; Staib, Lawrence H.; Duncan, James S.

2011-01-01

External beam radiotherapy (EBRT) has become the preferred options for non-surgical treatment of prostate cancer and cervix cancer. In order to deliver higher doses to cancerous regions within these pelvic structures (i.e. prostate or cervix) while maintaining or lowering the doses to surrounding non-cancerous regions, it is critical to account for setup variation, organ motion, anatomical changes due to treatment and intra-fraction motion. In previous work, manual segmentation of the soft tissues is performed and then images are registered based on the manual segmentation. In this paper, we present an integrated automatic approach to multiple organ segmentation and nonrigid constrained registration, which can achieve these two aims simultaneously. The segmentation and registration steps are both formulated using a Bayesian framework, and they constrain each other using an iterative conditional model strategy. We also propose a new strategy to assess cumulative actual dose for this novel integrated algorithm, in order to both determine whether the intended treatment is being delivered and, potentially, whether or not a plan should be adjusted for future treatment fractions. Quantitative results show that the automatic segmentation produced results that have an accuracy comparable to manual segmentation, while the registration part significantly outperforms both rigid and non-rigid registration. Clinical application and evaluation of dose delivery show the superiority of proposed method to the procedure currently used in clinical practice, i.e. manual segmentation followed by rigid registration. PMID:21646038

Hyperparathyroidism in persons exposed to iodine-131 from the Hanford Nuclear Site.

PubMed

Hamilton, Thomas E; Davis, Scott; Onstad, Lynn; Kopecky, Kenneth J

2005-12-01

The risk of primary hyperparathyroidism from exposure to external radiation has been well documented in the last 20 yr. However, it remains unclear whether hyperparathyroidism might also be caused by internal exposure to radioactive iodine. The objective of this study was to determine whether exposure to 131I from the Hanford Nuclear Site during 1944-1957 increased the risk of hyperparathyroidism among people living in the area. The Hanford Thyroid Disease Study was conducted as a retrospective cohort study. The study setting was the general community in Washington State. The participants were 5199 persons born to mothers with usual residence in one of seven counties in eastern Washington State, randomly selected from birth records for the years 1940-1946. Of the 5199 selected, 3440 underwent a Hanford Thyroid Disease Study clinical evaluation, including an evaluation for hyperparathyroidism. Individual thyroid radiation dose, which could be estimated for 3191 study participants, ranged from 0.0029-2823 mGy (mean, 174 mGy). Hyperparathyroidism was the main outcome measure. Of 3440 evaluable participants, we confirmed 12 cases of primary hyperparathyroidism (0.35%). We found no evidence that the cumulative incidence of hyperparathyroidism increased with increasing radiation dose. In summary, this study shows no evidence that 131I, received at young ages and at the doses and exposure conditions experienced by this cohort, increased the risk of primary hyperparathyroidism. However, the effects of different doses and conditions of exposure to 131I on the risk of hyperparathyroidism remain to be defined.

Special cases for proton beam radiotherapy: re-irradiation, lymphoma, and breast cancer.

PubMed

Plastaras, John P; Berman, Abigail T; Freedman, Gary M

2014-12-01

The dose distributions that can be achieved with protons are usually superior to those of conventional photon external-beam radiation. There are special cases where proton therapy may offer a substantial potential benefit compared to photon treatments where toxicity concerns dominate. Re-irradiation may theoretically be made safer with proton therapy due to lower cumulative lifetime doses to sensitive tissues, such as the spinal cord. Proton therapy has been used in a limited number of patients with rectal, pancreatic, esophageal, and lung cancers. Chordomas and soft tissue sarcomas require particularly high radiation doses, posing additional challenges for re-irradiation. Lymphoma is another special case where proton therapy may be advantageous. Late toxicities from even relatively low radiation doses, including cardiac complications and second cancers, are of concern in lymphoma patients with high cure rates and long life expectancies. Proton therapy has begun to be used for consolidation after chemotherapy in patients with Hodgkin and non-Hodgkin lymphoma. Breast cancer is another emerging area of proton therapy development and use. Proton therapy may offer advantages compared to other techniques in the setting of breast boosts, accelerated partial breast irradiation, and post-mastectomy radiotherapy. In these settings, proton therapy may decrease toxicity associated with breast radiotherapy. As techniques are refined in proton therapy, we may be able to improve the therapeutic ratio by maintaining the benefits of radiotherapy while better minimizing the risks. Copyright © 2014 Elsevier Inc. All rights reserved.

A prospective cohort study of exposure-response relationship for vibration-induced white finger.

PubMed

Bovenzi, M

2010-01-01

To investigate prospectively the relation between vibration-induced white finger (VWF) and measures of cumulative (lifetime) exposure to hand-transmitted vibration (HTV). Two hundred and forty-nine HTV workers and 138 control men of the same companies participated in a 3-year follow-up study. The diagnosis of VWF (Raynaud's phenomenon in the controls) was based on the medical history, the administration of colour charts and the results of a cold test. Tool vibration magnitudes were expressed as root-mean-square (r.m.s.) acceleration, frequency-weighted according to international standard ISO 5349-1 and also unweighted over the frequency range 6.3-1250 Hz. From the vibration magnitudes and exposure durations, alternative measures of cumulative vibration dose were calculated for each HTV worker, according to the expression: dose = Sigmaa(i)(m)t(i), where a(i) is the acceleration magnitude on tool i, t(i) is the lifetime exposure duration (hours) for tool i, and m = 0, 1, 2 or 4. The incidence of VWF varied from 5 to 6% in the HTV workers versus 0 to 1.5% for Raynaud's phenomenon in the controls. After adjusting for potential confounders, measures of cumulative vibration dose derived from total operating hours and high powers of unweighted acceleration (ie, , with m>1) gave better predictions of the occurrence of VWF than dose measures calculated from frequency-weighted acceleration (ie, ). These findings were observed in the entire sample of HTV workers, in those with no VWF at the initial investigation, and in those with normal cold test results at baseline. This prospective cohort study suggests that measures of cumulative vibration doses constructed from unweighted r.m.s. acceleration perform better for the prediction of VWF than dose measures calculated according to the recommendations of current standards. These findings should contribute to the improvement of the ISO frequency weighting for evaluating the severity of hand-transmitted vibration.

Survey on low-dose medical radiation exposure in occupational workers: the effect on hematological change

NASA Astrophysics Data System (ADS)

Ryu, J. K.; Cho, S. M.; Cho, J. H.; Dong, K. R.; Chung, W. K.; Lee, J. W.

2013-03-01

This study examined the changes in the hematological index caused by low-dose medical radiation exposure in workers in a medical radiation-exposed environment. The cumulative dose was obtained using thermoluminescent dosimeters over a 9-year period, and the changes in hematological index count (red blood cells (RBCs), hemoglobin, platelets, white blood cells (WBCs), monocytes, lymphocytes, neutrophils, basophils, and eosinophils) were examined in both the occupational workers and controls. In total, 370 occupational workers and 335 controls were compared. The analysis led to the following observations: (1) The average cumulative dose in males and females was 9.65±15.2 and 4.82±5.55 mSv, respectively. (2) In both males and females, there was a very low correlation between the occupation period and the cumulative dose (r<±0.25). (3) When the occupation period was longer, the WBC counts both decreased and increased in the male workers and the RBC counts were lower in the workers than in the control group (p<0.05). In females, the WBC counts both decreased and increased in the workers and the eosinophil counts were lower in the workers than in the control group (p<0.01). (4) When the cumulative dose was large, the lymphocyte counts decreased in male workers and the platelet count was lower in the workers than in the control group (p<0.05). In females, the lymphocyte count and RBC count were lower in the workers than in the control group (p<0.05). Abnormal distributions of some blood indices were observed in the occupational radiation workers compared with the controls. Attempts were made to limit radiation exposure to personnel, but the employees did not always follow the preset rules. Actually, the adverse effects of low-level radiation were attributed to probability. Overall, workers should obey the radiation protection regulations provided by the government and a national system of radiation protection is needed.

Studies on the bronchodilator, tremorogenic, cardiovascular and hypokalaemic effects of fenoterol dry powder in asthma.

PubMed Central

Bauer, K G; Kaik, B; Sertl, K; Kaik, G A

1993-01-01

1. The airway and tremor response and cardiovascular and hypokalaemic effects of single and cumulative doses of fenoterol given by dry powder capsules (DPC) and by metered dose inhaler (MDI) were studied in asthmatics in two randomized, crossover trials. 2. Single doses of fenoterol DPC and MDI (0.2 mg, 0.4 mg), investigated in 24 subjects, produced similar, dose-dependent increases in FEV1. Fenoterol DPC caused less tremor response and less hypokalaemic effects than fenoterol MDI. 3. Cumulative doses of fenoterol DPC and MDI (0.2, 0.6, 1.4, 3.0, 6.2 mg), investigated in 12 subjects, produced a comparable bronchodilatation (mean maximum increase in FEV1 was 0.53 +/- 0.06/0.52 +/- 0.081 for DPC/MDI) and a similar, dose-dependent rise in heart rate (35 +/- 3.81/41 +/- 2.25 beats min(-1)). The rise in tremor and the fall in plasma potassium were smaller after DPC than after MDI. The mean maximum changes were 51.58 +/- 6.41/95.83 +/- 6.75 cm s(-2) for tremor and -0.68 +/- 0.09/-0.96 +/- 0.10 mmol l(-1) for potassium. 4. Our findings may result from a difference in the pharmacokinetics of the dry powder and the aerosol formulation, particularly differences in distribution and absorption. 5. In conclusion, fenoterol DPC used in low therapeutic doses (0.2,0.4 mg), is preferable to the MDI. Fenoterol DPC used as rescue medication in high cumulative doses, do not suggest a greater safety margin than the MDI and the same restrictions should be considered for the fenoterol dry powder formulation as suggested for the MDI. PMID:12959305

Leukemia, lymphoma and multiple myeloma mortality (1950-1999) and incidence (1969-1999) in the Eldorado uranium workers cohort.

PubMed

Zablotska, Lydia B; Lane, Rachel S D; Frost, Stanley E; Thompson, Patsy A

2014-04-01

Uranium workers are chronically exposed to low levels of radon decay products (RDP) and gamma (γ) radiation. Risks of leukemia from acute and high doses of γ-radiation are well-characterized, but risks from lower doses and dose-rates and from RDP exposures are controversial. Few studies have evaluated risks of other hematologic cancers in uranium workers. The purpose of this study was to analyze radiation-related risks of hematologic cancers in the cohort of Eldorado uranium miners and processors first employed in 1932-1980 in relation to cumulative RDP exposures and γ-ray doses. The average cumulative RDP exposure was 100.2 working level months and the average cumulative whole-body γ-radiation dose was 52.2 millisievert. We identified 101 deaths and 160 cases of hematologic cancers in the cohort. Overall, male workers had lower mortality and cancer incidence rates for all outcomes compared with the general Canadian male population, a likely healthy worker effect. No statistically significant association between RDP exposure or γ-ray doses, or a combination of both, and mortality or incidence of any hematologic cancer was found. We observed consistent but non-statistically significant increases in risks of chronic lymphocytic leukemia (CLL) and Hodgkin lymphoma (HL) incidence and non-Hodgkin lymphoma (NHL) mortality with increasing γ-ray doses. These findings are consistent with recent studies of increased risks of CLL and NHL incidence after γ-radiation exposure. Further research is necessary to understand risks of other hematologic cancers from low-dose exposures to γ-radiation. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Individual external doses below the lowest reference level of 1 mSv per year five years after the 2011 Fukushima nuclear accident among all children in Soma City, Fukushima: A retrospective observational study.

PubMed

Tsubokura, Masaharu; Murakami, Michio; Nomura, Shuhei; Morita, Tomohiro; Nishikawa, Yoshitaka; Leppold, Claire; Kato, Shigeaki; Kami, Masahiro

2017-01-01

After the 2011 Fukushima Daiichi nuclear power plant accident, little information has been available on individual doses from external exposure among residents living in radioactively contaminated areas near the nuclear plant; in the present study we evaluated yearly changes in the doses from external exposure after the accident and the effects of decontamination on external exposure. This study considered all children less than 16 years of age in Soma City, Fukushima who participated in annual voluntary external exposure screening programs during the five years after the accident (n = 5,363). In total, 14,405 screening results were collected. The median participant age was eight years. The geometric mean levels of annual additional doses from external exposure attributable to the Fukushima accident, decreased each year: 0.60 mSv (range: not detectable (ND)-4.29 mSv), 0.37 mSv (range: ND-3.61 mSv), 0.22 mSv (range: ND-1.44 mSv), 0.20 mSv (range: ND-1.87 mSv), and 0.17 mSv (range: ND-0.85 mSv) in 2011, 2012, 2013, 2014, and 2015, respectively. The proportion of residents with annual additional doses from external exposure of more than 1 mSv dropped from 15.6% in 2011 to zero in 2015. Doses from external exposure decreased more rapidly than those estimated from only physical decay, even in areas without decontamination (which were halved in 395 days from November 15, 2011), presumably due to the weathering effects. While the ratios of geometric mean doses immediately after decontamination to before were slightly lower than those during the same time in areas without decontamination, annual additional doses reduced by decontamination were small (0.04-0.24 mSv in the year of immediately after decontamination was completed). The results of this study showed that the levels of external exposure among Soma residents less than 16 years of age decreased during the five years after the Fukushima Daiichi nuclear power plant accident. Decontamination had only limited and temporal effects on reducing individual external doses.

Cancer in the offspring of radiation workers: a record linkage study.

PubMed Central

Draper, G. J.; Little, M. P.; Sorahan, T.; Kinlen, L. J.; Bunch, K. J.; Conquest, A. J.; Kendall, G. M.; Kneale, G. W.; Lancashire, R. J.; Muirhead, C. R.; O'Connor, C. M.; Vincent, T. J.

1997-01-01

OBJECTIVES: To test the "Gardner hypothesis" that childhood leukaemia and non-Hodgkin lymphoma can be caused by fathers' exposure to ionising radiation before the conception of the child, and, more generally, to investigate whether such radiation exposure of either parent is a cause of childhood cancer. DESIGN: Case-control study. SETTING: Great Britain. SUBJECTS: 35,949 children diagnosed as having cancer, together with matched controls. MAIN OUTCOME MEASURES: Parental employment as radiation worker as defined by inclusion in the National Registry for Radiation Workers and being monitored for external radiation before conception of child; cumulative dose of external ionising radiation for various periods of employment before conception; dose during pregnancy. RESULTS: After cases studied by Gardner and colleagues were excluded, fathers of children with leukaemia or non-Hodgkin lymphoma were significantly more likely than fathers of controls to have been radiation workers (relative risk 1.77, 95% confidence interval 1.05 to 3.03) but there was no dose-response relation for any of the exposure periods studied; indeed, the association was greatest for those with doses below the level of detection. No increased risk was found for fathers with a lifetime preconception dose of 100 mSv or more, or with a dose in the 6 months before conception of 10 mSv or more. There was no increased risk for the group of other childhood cancers. Mothers' radiation work was associated with a significant increase of childhood cancer (relative risk 5.00, 1.42 to 26.94; based on 15 cases and 3 controls). Only four of the case mothers and no controls were radiation workers during pregnancy. CONCLUSIONS: These results do not support the hypothesis that paternal preconception irradiation is a cause of childhood leukaemia and non-Hodgkin lymphoma; the observed associations may be chance findings or results from exposure to infective or other agents. If there is any increased risk for the children of fathers who are radiation workers, it is small in absolute terms: in Britain the average risk by age 15 years is 6.5 per 10,000; our best estimate, using all available data, is that the increase is 5.4 per 10,000. For mothers, the numbers are too small for reliable estimates of the risk, if any, to be made. PMID:9393219

Risk Associated with Cumulative Oral Glucocorticoid Use in Patients with Giant Cell Arteritis in Real-World Databases from the USA and UK.

PubMed

Gale, Sara; Wilson, Jessica C; Chia, Jenny; Trinh, Huong; Tuckwell, Katie; Collinson, Neil; Dimonaco, Sophie; Jick, Susan; Meier, Christoph; Mohan, Shalini V; Sarsour, Khaled

2018-05-11

Treatment of giant cell arteritis (GCA) involves immediate initiation of high-dose glucocorticoid therapy with slow tapering of the dose over many months. Chronic exposure to glucocorticoids is associated with serious comorbidities. The objective of this analysis was to determine the glucocorticoid exposure and risk of glucocorticoid-related adverse events (AEs) in real-world patients with GCA. Data from the Truven Healthcare MarketScan ® database (from January 1, 2000, to June 30, 2015) and the Clinical Practice Research Datalink (CPRD; from January 1, 1995, to August 31, 2013) were used to retrospectively analyze patients aged ≥ 50 years with GCA in the USA and UK, respectively. Outcomes included oral glucocorticoid use (cumulative prednisone-equivalent exposure), glucocorticoid-related AEs and the association of AE risk with glucocorticoid exposure over 52 weeks. Of the 4804 patients in the US MarketScan database and 3973 patients in the UK CPRD database included, 71.3 and 74.6% were women and mean age was 73.4 and 73.0 years, respectively. Median starting glucocorticoid dose and cumulative glucocorticoid dose at 52 weeks were 20-50 mg/day and 4000-4800 mg, respectively. The most frequent glucocorticoid-related AEs were hypertension and eye, bone health, and glucose tolerance conditions. In the first year after diagnosis, the likelihood of any glucocorticoid-related AE was significantly increased for each 1 g increase in cumulative glucocorticoid dose in the US and UK cohorts (odds ratio [95% CI], 1.170 [1.063, 1.287] and 1.06 [1.03, 1.09], respectively; P < 0.05 for both). Similar trends were observed for the risk of glucocorticoid-related AEs over full follow-up (mean, USA: 3.9 years, UK: 6.3 years). In real-world patients with GCA, increased cumulative glucocorticoid exposure was associated with an increased risk of glucocorticoid-related AEs. F. Hoffmann-La Roche Ltd. Plain language summary available for this article.

Pediatric cleft palate patients show a 3- to 5-fold increase in cumulative radiation exposure from dental radiology compared with an age- and gender-matched population: a retrospective cohort study.

PubMed

Jacobs, Reinhilde; Pauwels, Ruben; Scarfe, William C; De Cock, Carl; Dula, Karl; Willems, Guy; Verdonck, An; Politis, Constantinus

2018-05-01

The objective of the study was to compare estimates of pediatric cumulative exposure and lifetime attributable risk (LAR) of radiation-induced cancer from dental radiology between cleft palate (CP) subjects and age- and gender-matched controls (non-CP), with and without orthodontic treatment. The radiation exposure frequency of CP subjects and non-CP controls with and without orthodontic treatment was compared for two-dimensional radiography (intra-oral, panoramic and cephalometric radiography), computed tomography (CT), and cone-beam CT (CBCT) using cumulative radiation dose as an estimate. From this dose estimate, the age- and gender-dependent risk for radiation-induced stochastic effects was calculated for each patient group. CP patients received more radiographic examinations than non-CP controls, with the exception of intra-oral radiographs. The cumulative dose to CP patients was considerably higher (1963 μSv at the age of 20 years) than non-CP patients with (597 μSv) and without (383 μSv) orthodontic treatment, primarily due to the higher frequency of CT scanning. Accordingly, CP patients had a three to five times higher LAR than non-CP patients. This study suggests a significantly higher lifetime radiation exposure to CP patients than non-CP controls from dental radiographic procedures. Diagnostic benefits from the use of CT and CBCT in children must be justified and appropriate dose optimization strategies implemented. The present study indicates the need for proper justification and optimization of pediatric exposures in dentistry, with a special focus on high-risk groups.

Demographic and socioenvironmental predictors of premorbid marijuana use among patients with first-episode psychosis.

PubMed

Pauselli, Luca; Birnbaum, Michael L; Vázquez Jaime, Beatriz Paulina; Paolini, Enrico; Kelley, Mary E; Broussard, Beth; Compton, Michael T

2018-01-31

We identified, in subjects with first-episode psychosis, demographic and socioenvironmental predictors of three variables pertaining to premorbid marijuana use: age at initiation of marijuana use, trajectories of marijuana use in the five years prior to onset of psychosis, and the cumulative "dose" of marijuana intake in that same premorbid period. We enrolled 247 first-episode psychosis patients and collected data on lifetime marijuana/alcohol/tobacco use, age at onset of psychosis, diverse socioenvironmental variables, premorbid adjustment, past traumatic experiences, perceived neighborhood-level social disorder, and cannabis use experiences. Bivariate tests were used to examine associations between the three premorbid marijuana use variables and hypothesized predictors. Regression models determined which variables remained independently significantly associated. Age at initiation of cigarette smoking was linked to earlier initiation, faster escalation, and higher cumulative dose of premorbid marijuana use. During childhood, poorer academic performance was predictive of an earlier age at initiation of marijuana use, while poorer sociability was related to more rapid escalation to daily use and a higher cumulative dose. As expected, experiencing euphoric effects was positively correlated with trajectories and cumulative dose, but having negative experiences was unrelated. Traumatic childhood/adolescent experiences were correlated with rapid escalation and amount of marijuana used, but not with age at initiation of marijuana use. These data expand the very limited literature on predictors of premorbid marijuana use in first-episode psychosis. Given its association with earlier age at onset of psychosis, and poorer outcomes among first-episode patients, prevention and treatment efforts should be further developed. Copyright © 2018 Elsevier B.V. All rights reserved.

RISK ASSESSMENT FOR CRYPTOSPORIDIUM: A HIERARCHICAL BAYESIAN ANALYSIS OF HUMAN DOSE-RESPONSE DATA. (R828035)

EPA Science Inventory

Three dose_¯response studies were conducted with healthy volunteers using different Cryptosporidium parvum isolates (IOWA, TAMU, and UCP). The study data were previously analyzed for median infectious dose (ID₅₀) using a simple cumulative perce...

Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 2: The predicted hyper responder.

PubMed

Oudshoorn, Simone C; van Tilborg, Theodora C; Eijkemans, Marinus J C; Oosterhuis, G Jur E; Friederich, Jaap; van Hooff, Marcel H A; van Santbrink, Evert J P; Brinkhuis, Egbert A; Smeenk, Jesper M J; Kwee, Janet; de Koning, Corry H; Groen, Henk; Lambalk, Cornelis B; Mol, Ben Willem J; Broekmans, Frank J M; Torrance, Helen L

2017-12-01

Does a reduced FSH dose in women with a predicted hyper response, apparent from a high antral follicle count (AFC), who are scheduled for IVF/ICSI lead to a different outcome with respect to cumulative live birth rate and safety? Although in women with a predicted hyper response (AFC > 15) undergoing IVF/ICSI a reduced FSH dose (100 IU per day) results in similar cumulative live birth rates and a lower occurrence of any grade of ovarian hyperstimulation syndrome (OHSS) as compared to a standard dose (150 IU/day), a higher first cycle cancellation rate and similar severe OHSS rate were observed. Excessive ovarian response to controlled ovarian stimulation (COS) for IVF/ICSI may result in increased rates of cycle cancellation, the occurrence of OHSS and suboptimal live birth rates. In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can be used to predict response to COS. No consensus has been reached on whether ORT-based FSH dosing improves effectiveness and safety in women with a predicted hyper response. Between May 2011 and May 2014, we performed an open-label, multicentre RCT in women with regular menstrual cycles and an AFC > 15. Women with polycystic ovary syndrome (Rotterdam criteria) were excluded. The primary outcome was ongoing pregnancy achieved within 18 months after randomization and resulting in a live birth. Secondary outcomes included the occurrence of OHSS and cost-effectiveness. Since this RCT was embedded in a cohort study assessing over 1500 women, we expected to randomize 300 predicted hyper responders. Women with an AFC > 15 were randomized to an FSH dose of 100 IU or 150 IU/day. In both groups, dose adjustment was allowed in subsequent cycles (maximum 25 IU in the reduced and 50 IU in the standard group) based on pre-specified criteria. Both effectiveness and cost-effectiveness were evaluated from an intention-to-treat perspective. We randomized 255 women to a daily FSH dose of 100 IU and 266 women to a daily FSH dose of 150 IU. The cumulative live birth rate was 66.3% (169/255) in the reduced versus 69.5% (185/266) in the standard group (relative risk (RR) 0.95 [95%CI, 0.85-1.07], P = 0.423). The occurrence of any grade of OHSS was lower after a lower FSH dose (5.2% versus 11.8%, RR 0.44 [95%CI, 0.28-0.71], P = 0.001), but the occurrence of severe OHSS did not differ (1.3% versus 1.1%, RR 1.25 [95%CI, 0.38-4.07], P = 0.728). As dose reduction was not less expensive (€4.622 versus €4.714, delta costs/woman €92 [95%CI, -479-325]), there was no dominant strategy in the economic analysis. Despite our training programme, the AFC might have suffered from inter-observer variation. Although strict cancellation criteria were provided, selective cancelling in the reduced dose group (for poor response in particular) cannot be excluded as observers were not blinded for the FSH dose and small dose adjustments were allowed in subsequent cycles. However, as first cycle live birth rates did not differ from the cumulative results, the open design probably did not mask a potential benefit for the reduced dosing group. As this RCT was embedded in a larger cohort study, the power in this study was unavoidably lower than it should be. Participants had a relatively low BMI from an international perspective, which may limit generalization of the findings. In women with a predicted hyper response scheduled for IVF/ICSI, a reduced FSH dose does not affect live birth rates. A lower FSH dose did reduce the incidence of mild and moderate OHSS, but had no impact on severe OHSS. Future research into ORT-based dosing in women with a predicted hyper response should compare various safety management strategies and should be powered on a clinically relevant safety outcome while assessing non-inferiority towards live birth rates. This trial was funded by The Netherlands Organization for Health Research and Development (ZonMW, Project Number 171102020). SCO, TCvT and HLT received an unrestricted research grant from Merck Serono (the Netherlands). CBL receives grants from Merck, Ferring and Guerbet. BWJM is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for OvsEva, Merck and Guerbet. FJMB receives monetary compensation as a member of the external advisory board for Ferring pharmaceutics BV and Merck Serono for consultancy work for Gedeon Richter (Belgium) and Roche Diagnostics (Switzerland) and for a research cooperation with Ansh Labs (USA). All other authors have nothing to declare. Registered at the ICMJE-recognized Dutch Trial Registry (www.trialregister.nl). Registration number: NTR2657. 20 December 2010. 12 May 2011. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

SU-F-J-63: Abdominal Diameter Changes in Children During Volumetric Modulated Arc Therapy (VMAT): Is Re-Planning Needed?

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

Guerreiro, F; Janssens, G; Seravalli, E

Purpose: To investigate the dosimetric impact of daily changes in patient’s diameter, due to weight gain/loss and air in the bowel, based on CBCT information during radiotherapy treatment of pediatric abdominal tumors. Methods: 10 pediatric patients with neuroblastoma (n=6) and Wilms’ (n=4) tumors were included. Available CBCTs were affinely registered to the planning CT for daily set-up variations corrections. A density override approach assigning air-density to the random air pockets and water-density to the remaining anatomy was used to determine the CBCT and CT dose. Clinical VMAT plans, with a PTV prescribed dose ranging between (14.4- 36) Gy, were re-optimizedmore » on the density override CT and re-calculated on each CBCT. Dose-volume statistics of the PTV and kidneys, delineated on each CBCT, were used to compare the daily and cumulative CBCT dose with the reference CT dose. Results: The average patient diameter variation was (0.5 ± 0.7) cm (maximum daily difference of 2.3 cm). The average PTV mean dose difference (MDD) between the CT and the cumulative CBCT plans was (0.1 ± 1.1) % (maximum daily MDD of 2%). A reduction in target coverage up to 3% and 7% was observed for the cumulative and daily CBCT plans, respectively. The average kidneys’ cumulative MDD was (−2.7 ± 3.6) % (maximum daily MDD of −12%), corresponding to an overdosage. Conclusion: Due to patient’s diameter changes, a target underdosage was assessed. Given the high local tumor control of neuroblastoma and Wilms’ diseases, the need of re-planning might be discarded. However, the assessed kidneys overdosage could represent a problem when the normal tissue tolerance is reached. The necessity of re-planning should then be considered to reduce the risk of long-term renal complications. Due to the poor softtissue contrast on CBCT, MRI-guidance is required to obtain a better assessment of the accumulated dose on the remaining OARs.« less

Aluminum/vacuum multilayer configuration for spatial high-energy electron shielding via electron return effects induced by magnetic field.

PubMed

Chen, Tuo; Tang, Xiaobin; Chen, Feida; Ni, Minxuan; Huang, Hai; Zhang, Yun; Chen, Da

2017-06-26

Radiation shielding of high-energy electrons is critical for successful space missions. However, conventional passive shielding systems exhibit several limitations, such as heavy configuration, poor shielding ability, and strong secondary bremsstrahlung radiation. In this work, an aluminum/vacuum multilayer structure was proposed based on the electron return effects induced by magnetic field. The shielding property of several configurations was evaluated by using the Monte Carlo method. Results showed that multilayer systems presented improved shielding ability to electrons, and less secondary x-ray transmissions than those of conventional systems. Moreover, the influences of magnetic flux density and number of layers on the shielding property of multilayer systems were investigated using a female Chinese hybrid reference phantom based on cumulative dose. In the case of two aluminum layers, the cumulative dose in a phantom gradually decreased with increasing magnetic flux density. The maximum decline rate was found within 0.4-1 Tesla. With increasing layers of configuration, the cumulative dose decreased and the shielding ability improved. This research provides effective shielding measures for future space radiation protection in high-energy electron environments.

A Comparison Between Low-Dose-Rate Brachytherapy With or Without Androgen Deprivation, External Beam Radiation Therapy With or Without Androgen Deprivation, and Radical Prostatectomy With or Without Adjuvant or Salvage Radiation Therapy for High-Risk Prostate Cancer

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

Ciezki, Jay P., E-mail: ciezkij@ccf.org; Weller, Michael; Reddy, Chandana A.

Purpose: We compare the efficacy and toxicity among the 3 major modalities available used to treat high-risk prostate cancer (HRCaP). Methods and Materials: From 1996 to 2012, 2557 HRCaP patients were treated: 734 received external beam radiation therapy (EBRT) with or without androgen deprivation therapy (ADT), 515 received low-dose-rate prostate brachytherapy (LDR) with or without ADT, and 1308 received radical prostatectomy (RP) with or without EBRT. Biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), and prostate cancer–specific mortality (PCSM) were assessed. Toxicity was assessed using the Common Terminology Criteria for Adverse Events, version 4.03. The log-rank test compared bRFS andmore » cRFS among the modalities, and Cox regression identified factors associated with bRFS and cRFS. Gray's test compared differences in late toxicity and PSCM among the modalities. Competing risk regression identified factors associated with PCSM. Results: The median follow-up time and age were 63.5 months and 65 years, respectively. The bRFS at 5 and 10 years, respectively, was 74% and 53% for EBRT, 74% and 52% for LDR, and 65% and 47% for RP (P=.0001). The cRFS at 5 and 10 years, respectively, was 85% and 73% for EBRT, 90% and 76% for LDR, and 89% and 75% for RP (P=.121). The PCSM at 5 and 10 years, respectively, was 5.3% and 11.2% for EBRT, 3.2% and 3.6% for LDR, and 2.8% and 6.8% for RP (P=.0004). The 10-year cumulative incidence of ≥grade 3 genitourinary toxicity was 8.1% for EBRT, 7.2% for LDR, and 16.4% for RP (P<.0001). The 10-year cumulative incidence of ≥grade 3 gastrointestinal toxicity was 4.6% for EBRT, 1.1% for LDR, and 1.0% for RP (P<.0001). Conclusion: HRCaP treated with EBRT, LDR, or RP yields efficacy showing better bRFS for LDR and EBRT relative to RP, equivalence for cRFS, and a PCSM advantage of LDR and RP over EBRT. The toxicity is lowest for LDR.« less

A Comparison Between Low-Dose-Rate Brachytherapy With or Without Androgen Deprivation, External Beam Radiation Therapy With or Without Androgen Deprivation, and Radical Prostatectomy With or Without Adjuvant or Salvage Radiation Therapy for High-Risk Prostate Cancer.

PubMed

Ciezki, Jay P; Weller, Michael; Reddy, Chandana A; Kittel, Jeffrey; Singh, Harguneet; Tendulkar, Rahul; Stephans, Kevin L; Ulchaker, James; Angermeier, Kenneth; Stephenson, Andrew; Campbell, Steven; Haber, Georges-Pascal; Klein, Eric A

2017-04-01

We compare the efficacy and toxicity among the 3 major modalities available used to treat high-risk prostate cancer (HRCaP). From 1996 to 2012, 2557 HRCaP patients were treated: 734 received external beam radiation therapy (EBRT) with or without androgen deprivation therapy (ADT), 515 received low-dose-rate prostate brachytherapy (LDR) with or without ADT, and 1308 received radical prostatectomy (RP) with or without EBRT. Biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), and prostate cancer-specific mortality (PCSM) were assessed. Toxicity was assessed using the Common Terminology Criteria for Adverse Events, version 4.03. The log-rank test compared bRFS and cRFS among the modalities, and Cox regression identified factors associated with bRFS and cRFS. Gray's test compared differences in late toxicity and PSCM among the modalities. Competing risk regression identified factors associated with PCSM. The median follow-up time and age were 63.5 months and 65 years, respectively. The bRFS at 5 and 10 years, respectively, was 74% and 53% for EBRT, 74% and 52% for LDR, and 65% and 47% for RP (P=.0001). The cRFS at 5 and 10 years, respectively, was 85% and 73% for EBRT, 90% and 76% for LDR, and 89% and 75% for RP (P=.121). The PCSM at 5 and 10 years, respectively, was 5.3% and 11.2% for EBRT, 3.2% and 3.6% for LDR, and 2.8% and 6.8% for RP (P=.0004). The 10-year cumulative incidence of ≥grade 3 genitourinary toxicity was 8.1% for EBRT, 7.2% for LDR, and 16.4% for RP (P<.0001). The 10-year cumulative incidence of ≥grade 3 gastrointestinal toxicity was 4.6% for EBRT, 1.1% for LDR, and 1.0% for RP (P<.0001). HRCaP treated with EBRT, LDR, or RP yields efficacy showing better bRFS for LDR and EBRT relative to RP, equivalence for cRFS, and a PCSM advantage of LDR and RP over EBRT. The toxicity is lowest for LDR. Copyright © 2016 Elsevier Inc. All rights reserved.

Ranitidine Can Potentiate The Prokinetic Effect Of Itopride At Low Doses- An In Vitro Study.

PubMed

Butt, Aroosa Ishtiaq; Khan, Bushra Tayyaba; Khan, Asma; Khan, Qamar-Uz-Zaman

2017-01-01

Gastroparesis and GERD occur concomitantly in 40 percent of the cases. Prokinetic drugs and acid blockers are employed as the main treatment modality. Ranitidine is an acid blocker with additional prokinetic activity and Itopride is a known prokinetic drug. This study was designed to observe the synergistic potentiating prokinetic effect of Ranitidine on itopride on isolated duodenum of rabbits. Ranitidine (10-5-10-3) and itopride (10-6-10-5) were added in increasing concentrations to isolated duodenum of rabbits and contractions were recorded on PowerLab Data acquisition unit AHK/214. Cumulative dose response curves were constructed. The potentiating prokinetic effect of Ranitidine on itopride was seen by using a fixed dose of ranitidine and cumulatively enhancing doses of itopride on iWorx. Ranitidine and itopride produced a dose dependent reversible contraction of the isolated tissue of rabbits with ranitidine showing a max response of 0.124mV and itopride showing a maximum response of 0.131mV. Ranitidine was able to potentiate the prokinetic effect of itopride at low doses but at high dose the effect began to wane off. Ranitidine and itopride produce a statistically significant synergistic potentiating prokinetic effect at low doses in vitro.

Low-Dose N,N-Dimethylformamide Exposure and Liver Injuries in a Cohort of Chinese Leather Industry Workers.

PubMed

Qi, Cong; Gu, Yiyang; Sun, Qing; Gu, Hongliang; Xu, Bo; Gu, Qing; Xiao, Jing; Lian, Yulong

2017-05-01

We assessed the risk of liver injuries following low doses of N,N-dimethylformamide (DMF) below threshold limit values (20 mg/m) among leather industry workers and comparison groups. A cohort of 429 workers from a leather factory and 466 non-exposed subjects in China were followed for 4 years. Poisson regression and piece-wise linear regression were used to examine the relationship between DMF and liver injury. Workers exposed to a cumulative dose of DMF were significantly more likely than non-exposed workers to develop liver injury. A nonlinear relationship between DMF and liver injury was observed, and a threshold of the cumulative DMF dose for liver injury was 7.30 (mg/m) year. The findings indicate the importance of taking action to reduce DMF occupational exposure limits for promoting worker health.

(BOSC) DOSE-RESPONSE MODELING FOR THE ASSESSMENT OF CUMULATIVE RISK DUE TO EXPOSURE TO N-METHYL CARBAMATE PRESTICIDES

EPA Science Inventory

THE US EPA'S N-METHYL CARBAMATE CUMULATIVE RISK ASSESSMENT (NMCRA) ASSESSES THE EFFECT ON ACETYLCHOLINE ESTERASE (AChE) ACTIVITY OF EXPOSURE TO 10 N-METHLY CARBAMATE (NMC)PESTICIDES THROUGH DIETARY, DRINKING WATER, AND RESIDENTIAL EXPOSURES. THESE DATA THUS INFORM, BUT DO NOT COM...

The biodistribution and dosimetry of {sup 117m}Sn DTPA with special emphasis on active marrow absorbed doses

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

Stubbs, J.; Atkins, H.

1999-01-01

{sup 117m}Sn(4+) DTPA is a new radiopharmaceutical for the palliation of pain associated with metastatic bone cancer. Recently, the Phase 2 clinical trials involving 47 patients were completed. These patients received administered activities in the range 6.7--10.6 MBq/kg of body mass. Frequent collections of urine were acquired over the first several hours postadministration and daily cumulative collections were obtained for the next 4--10 days. Anterior/posterior gamma camera images were obtained frequently over the initial 10 days. Radiation dose estimates were calculated for 8 of these patients. Each patient`s biodistribution data were mathematically simulated using a multicompartmental model. The model consistedmore » of the following compartments: central, bone, kidney, other tissues, and cumulative urine. The measured cumulative urine data were used as references for the cumulative urine excretion compartment. The total-body compartment (sum of the bone surfaces, central, kidney, and other tissues compartments) was reference to all activity not excreted in the urine.« less

Low-Dose Aspirin Reduces Breast Cancer Risk in Women with Diabetes: A Nationwide Retrospective Cohort Study in Taiwan.

PubMed

Yang, Yi-Sun; Kornelius, Edy; Chiou, Jeng-Yuan; Lai, Yung-Rung; Lo, Shih-Chang; Peng, Chiung-Huei; Huang, Chien-Ning

2017-12-01

Low-dose aspirin is commonly used for preventing cardiovascular disease in people with diabetes, but its association with cancer remains controversial. This study used a nationwide population-based reimbursement database to investigate the relationship between low-dose aspirin use and breast cancer incidence in women with diabetes. This retrospective cohort study was conducted using data retrieved from the National Health Insurance Research Database in Taiwan from January 1, 1998 to December 31, 2011. Women diagnosed as having diabetes with low-dose aspirin use (75-165 mg daily) were identified as the study population, whereas those without low-dose aspirin use were selected as the comparison group. We analyzed 148,739 patients with diabetes. Their mean age (standard deviation) was 63.3 (12.8) years. A total of 27,378 patients were taking aspirin. Overall, the use of aspirin in patients with diabetes reduced the risk of breast cancer by 18% (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.71-0.94) after adjustment for potential confounders, namely age and comorbidities. Specifically, a cumulative dose of aspirin exceeding 88,900 mg was observed to reduce the risk of breast cancer by 47% (HR, 0.53, 95% CI, 0.43-0.67); however, low (<8,600 mg) and medium (8,600-88,900 mg) cumulative doses of aspirin did not reduce the risk of breast cancer. Our findings suggest that a cumulative aspirin dosage of more than 88,900 mg daily was associated with a reduced risk of breast cancer in women with diabetes. However, additional studies are necessary to confirm these findings.

Radiation exposure during in-situ pinning of slipped capital femoral epiphysis hips: does the patient positioning matter?

PubMed

Mohammed, Riazuddin; Johnson, Karl; Bache, Ed

2010-07-01

Multiple radiographic images may be necessary during the standard procedure of in-situ pinning of slipped capital femoral epiphysis (SCFE) hips. This procedure can be performed with the patient positioned on a fracture table or a radiolucent table. Our study aims to look at any differences in the amount and duration of radiation exposure for in-situ pinning of SCFE performed using a traction table or a radiolucent table. Sixteen hips in thirteen patients who were pinned on radiolucent table were compared for the cumulative radiation exposure to 35 hips pinned on a fracture table in 33 patients during the same time period. Cumulative radiation dose was measured as dose area product in Gray centimeter2 and the duration of exposure was measured in minutes. Appropriate statistical tests were used to test the significance of any differences. Mean cumulative radiation dose for SCFE pinned on radiolucent table was statistically less than for those pinned on fracture table (P<0.05). The mean duration of radiation exposure on either table was not significantly different. Lateral projections may increase the radiation doses compared with anteroposterior projections because of the higher exposure parameters needed for side imaging. Our results showing decreased exposure doses on the radiolucent table are probably because of the ease of a frog leg lateral positioning obtained and thereby the ease of lateral imaging. In-situ pinning of SCFE hips on a radiolucent table has an additional advantage that the radiation dose during the procedure is significantly less than that of the procedure that is performed on a fracture table.

Identifying the health risks from very low-dose sparsely ionizing radiation

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

Dreyer, N.A.; Friedlander, E.

1982-01-01

The health risks from low-dose sparsely ionizing (low-LET) radiation have been the subject of continued debate. At present, quantitative estimates of risk are extremely uncertain due to the controversy surrounding both the dosimetry for A-bomb survivor data and the choice of mathematical models for extrapolating risk from high to low doses. Nevertheless, much can be learned about the nature of the health risks by reviewing the epidemiologic literature. We present a summary of diseases which have been associated with low-LET radiation (<1000 rad) in at least two independent studies, according to the mean cumulative organ dose at which the diseasemore » was observed. At organ doses of less than or equal to50 rad, the only diseases that have been reported consistently are thyroid cancer, salivary gland tumors, and leukemia. The first two diseases were observed in association with x-ray epilation of the scalp for tinea capitis, a therapy which is no longer employed. On the other hand, leukemia has been observed repeatedly to occur at cumulative doses of greater than or equal to30 rad low-LET radiation.« less

UVER and UV index at high altitude in Northwestern Argentina.

PubMed

Utrillas, M P; Marín, M J; Esteve, A R; Salazar, G; Suarez, H; Castillo, J; Martínez-Lozano, J A

2016-10-01

Measurements of ultraviolet erythemal radiation (UVER) made during two years at three sites located at altitudes over 1000ma.s.l. in Northwestern Argentina (Salta, San Carlos, and El Rosal) have been used to estimate and analyze the UV Index (UVI) and the cumulative doses at these locations. For the UVER irradiance, data of January (maximum values) and June (minimum values) have been analyzed as representative of the year for all locations. The UVI reaches extreme (>11) values in >20% of the analyzed days in Salta (1190ma.s.l.), while these are reached in San Carlos (1611ma.s.l.) and El Rosal (3355ma.s.l.) in >40% of the analyzed days. Finally, the cumulative doses over an average year have also been studied for each location. The doses received during austral summer and autumn are of the same order, and represent one third of the annual dose, while the doses received during austral winter and spring represent one sixth of the annual dose approximately. Copyright © 2016 Elsevier B.V. All rights reserved.

A summary of evidence on radiation exposures received near to the Semipalatinsk nuclear weapons test site in Kazakhstan.

PubMed

Simon, Steven L; Baverstock, Keith F; Lindholm, Carita

2003-06-01

The presently available evidence about the magnitude of doses received by members of the public living in villages in the vicinity of Semipalatinsk nuclear test in Kazakhstan, particularly with respect to external radiation, while preliminary, is conflicting. The village of Dolon, in particular, has been identified for many years as the most highly exposed location in the vicinity of the test site. Previous publications cited external doses of more than 2 Gy to residents of Dolon while an expert group assembled by the WHO in 1997 estimated that external doses were likely to have been less than 0.5 Gy. In 2001, a larger expert group workshop was held in Helsinki jointly by the WHO, the National Cancer Institute of the United States, and the Radiation and Nuclear Safety Authority of Finland, with the expressed purpose to acquire data to evaluate the state of knowledge concerning doses received in Kazakhstan. This paper summarizes evidence presented at that workshop. External dose estimates from calculations based on sparse physical measurements and bio-dosimetric estimates based on chromosome abnormalities and electron paramagnetic resonance from a relatively small sample of teeth do not agree well. The physical dose estimates are generally higher than the biodosimetric estimates (1 Gy or more compared to 0.5 Gy or less). When viewed in its entirety, the present body of evidence does not appear to support external doses greater than 0.5 Gy; however, research is continuing to try and resolve the difference in dose estimates from the different methods. Thyroid doses from internal irradiation, which can only be estimated via calculation, are expected to have been several times greater than the doses from external irradiation, especially where received by small children.

beta- and gamma-Comparative dose estimates on Enewetak Atoll.

PubMed

Crase, K W; Gudiksen, P H; Robison, W L

1982-05-01

Enewetak Atoll is one of the Pacific atolls used for atmospheric testing of U.S. nuclear weapons. Beta dose and gamma-ray exposure measurements were made on two islands of the Enewetak Atoll during July-August 1976 to determine the beta and low energy gamma-contribution to the total external radiation doses to the returning Marshallese. Measurements were made at numerous locations with thermoluminescent dosimeters (TLD), pressurized ionization chambers, portable NaI detectors, and thin-window pancake GM probes. Results of the TLD measurements with and without a beta-attenuator indicate that approx. 29% of the total dose rate at 1 m in air is due to beta- or low energy gamma-contribution. The contribution at any particular site, however, is somewhat dependent on ground cover, since a minimal amount of vegetation will reduce it significantly from that over bare soil, but thick stands of vegetation have little effect on any further reductions. Integral 30-yr external shallow dose estimates for future inhabitants were made and compared with external dose estimates of a previous large scale radiological survey (En73). Integral 30-yr shallow external dose estimates are 25-50% higher than whole body estimates. Due to the low penetrating ability of the beta's or low energy gamma's, however, several remedial actions can be taken to reduce the shallow dose contribution to the total external dose.

ESTIMATING CONTAMINANT DOSE FOR INTERMITTENT DERMAL CONTACT: MODEL DEVELOPMENT, TESTING, AND APPLICATION

EPA Science Inventory

Assessments of aggregate exposure to pesticides and other surface contamination in residential environments are often driven by assumptions about dermal contacts. Accurately predicting cumulative doses from realistic skin contact scenarios requires characterization of exposure sc...

Individual external doses below the lowest reference level of 1 mSv per year five years after the 2011 Fukushima nuclear accident among all children in Soma City, Fukushima: A retrospective observational study

PubMed Central

Murakami, Michio; Nomura, Shuhei; Morita, Tomohiro; Nishikawa, Yoshitaka; Leppold, Claire; Kato, Shigeaki; Kami, Masahiro

2017-01-01

After the 2011 Fukushima Daiichi nuclear power plant accident, little information has been available on individual doses from external exposure among residents living in radioactively contaminated areas near the nuclear plant; in the present study we evaluated yearly changes in the doses from external exposure after the accident and the effects of decontamination on external exposure. This study considered all children less than 16 years of age in Soma City, Fukushima who participated in annual voluntary external exposure screening programs during the five years after the accident (n = 5,363). In total, 14,405 screening results were collected. The median participant age was eight years. The geometric mean levels of annual additional doses from external exposure attributable to the Fukushima accident, decreased each year: 0.60 mSv (range: not detectable (ND)–4.29 mSv), 0.37 mSv (range: ND–3.61 mSv), 0.22 mSv (range: ND–1.44 mSv), 0.20 mSv (range: ND–1.87 mSv), and 0.17 mSv (range: ND–0.85 mSv) in 2011, 2012, 2013, 2014, and 2015, respectively. The proportion of residents with annual additional doses from external exposure of more than 1 mSv dropped from 15.6% in 2011 to zero in 2015. Doses from external exposure decreased more rapidly than those estimated from only physical decay, even in areas without decontamination (which were halved in 395 days from November 15, 2011), presumably due to the weathering effects. While the ratios of geometric mean doses immediately after decontamination to before were slightly lower than those during the same time in areas without decontamination, annual additional doses reduced by decontamination were small (0.04–0.24 mSv in the year of immediately after decontamination was completed). The results of this study showed that the levels of external exposure among Soma residents less than 16 years of age decreased during the five years after the Fukushima Daiichi nuclear power plant accident. Decontamination had only limited and temporal effects on reducing individual external doses. PMID:28235009

Radiation exposure of ventilated trauma patients in intensive care: a retrospective study comparing two time periods.

PubMed

Yee, Micaela V; Barron, Rochelle A; Knobloch, Tom A; Pandey, Umesh; Twyford, Catherine; Freebairn, Ross C

2012-08-01

To describe the cumulative effective dose of radiation that was received during the initial Emergency Department assessment and ICU stay of patients admitted with trauma, who required mechanical ventilation, during two time periods. A retrospective analysis of radiological and clinical data, set in a regional nonurban ICU. Two cohorts (starting 1 January 2004 and 1 January 2009), each comprising 45 adult patients admitted with trauma who were mechanically ventilated in intensive care, were studied. Frequency and type of radiological examinations, demographic information, and clinical data were collated from the radiological database, hospital admission record and Australian Outcomes Research Tool for Intensive Care database. Cumulative effective doses were calculated and expressed as a total dose and average daily dose for each cohort. The median cumulative effective dose per patient (in milliSieverts) increased from 34.59 [interquartile range (IQR) 9.08-43.91] in 2004 to 40.51 (IQR 22.01-48.87) in 2009, P=0.045. An increased number of computed tomography examinations per patient was also observed over the same interval from an average of 2.11 (median 2, IQR 1-3) in 2004 to an average of 2.62 (2, 2-4) in 2009, P=0.046. The radiation exposure of mechanically ventilated trauma patients in intensive care has increased over time. Radiation exposure should be prospectively monitored and staff should be aware of the increased risk resulting from this change in practice.

Predicting Late Effects of Pelvic Radiotherapy: Is There a Better Approach?

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

Wedlake, Linda J.; Thomas, Karen B.Sc.; Lalji, Amyn

2010-11-15

Purpose: Significant chronic symptoms following pelvic radiotherapy occur more frequently than commonly realized. Predictive factors for the development of late symptoms are poorly defined. Moderate sustained acute (cumulative) toxicity might predict severe late effects better than peak reaction. Methods and Materials: To determine prospectively whether peak or cumulative gastrointestinal (GI) acute symptoms better predict late symptoms in patients receiving pelvic radiotherapy. Symptom scores were measured weekly from the start of radiotherapy, and at 1 year using the Modified Inflammatory Bowel Disease Questionnaire-Bowel subset. The possible prognostic impact of patient-related factors was explored. Results: Three hundred and eight patients were recruited.more » 100 were excluded due to lack of follow-up data at one year resulting from death, too ill, stoma, relapsed, non-response or withdrawal. A further 15 were excluded for incomplete data, leaving 193 patients with evaluable data. Of these, 28 had GI, 101 urological, and 64 gynecological cancers. Patients' median age was 65 years (range, 23-82), and they were treated with median 60 Gy dose for a median of 6 weeks. Univariate analysis revealed a significant association between cumulative acute symptom scores and scores at 1 year (p < 0.001), which was dose-independent (p < 0.001). Acute peak and 1-year scores were not associated (p = 0.431). The correlation coefficient between cumulative acute symptoms and symptoms at 1 year was 0.367 and for peak acute symptoms was weaker at 0.057. Patients with an abnormal body mass index and current smokers were more likely to experience worse symptoms at 1 year. Conclusion: Cumulative acute symptoms are more predictive of late symptoms than peak acute changes in score. This association is independent of the radiotherapy dose delivered and is suggestive of a consequential late effect.« less

In vitro comparison of the antiproliferative effects of rhenium-186 and rhenium-188 on human aortic endothelial cells.

PubMed

Sauter, Alexander; Arthasana, Daniel; Dittmann, Helmut; Pritzkow, Maren; Wiesinger, Benjamin; Schmehl, Joerg; Brechtel, Klaus; Bantleon, Rüdiger; Claussen, Claus; Kehlbach, Rainer

2011-08-01

Rhenium-186 ((186)Re) and rhenium-188 ((188)Re) are promising radionuclides for the inhibition of restenosis after percutaneous transluminal angioplasty or other vascular interventions. Until now the maximal dose tolerance of endothelial cells has not been clearly known. To characterize the effects of local irradiation treatment, human aortic endothelial cells (ECs) were incubated with different doses of (186)Re and (188)Re. Two days after plating, ECs received treatment for a period of 5 days. The total radiation doses applied were 1, 4, 8, 16, and 32 Gy. On days 1, 3, 5, 7, and 12 after initial rhenium incubation, cell growth, clonogenic activity, cell-cycle distribution, and cytoskeletal architecture were evaluated. From the first day on, a dose-dependent growth inhibition was observed. Cumulative doses of ≥32 Gy caused a weak colony formation and significant alterations in the cytoskeletal architecture. An increased fraction of cells in G2/M phase was seen for cumulative radiation doses of ≥16 Gy. Interestingly, there were no significant differences between (186)Re and (188)Re. Even for low dose rates of β particles a dose-dependent proliferation inhibition of ECs is seen. Doses beyond 32 Gy alter the cytoskeletal architecture with possibly endothelial dysfunction and late thrombosis.

Dosimetry in differentiated thyroid carcinoma (12-1402R)

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

Minguez, Pablo; Genolla, Jose; Celeiro, Jose Javier

2013-01-15

Purpose: The aim of this study has been to perform a dosimetric study in the treatments of differentiated thyroid cancer (DTC) performed in our center in order to find a dose-effect correlation. Methods: Thirty patients treated for DTC with 3700 MBq of {sup 131}I have been included in this study. For reasons of radiological protection all of them spent two nights as inpatients. Dose rate at 1 m from all patients was measured approximately 20 and 44 h after the administration of the radioiodine and a whole body scan in the gamma camera was performed approximately 1 week later. Withmore » those measurements and by using a model of two compartments the activities in thyroid bed remnants and in the whole body were calculated as a function of time. The integration of both activities yields the corresponding cumulated activities. Absorbed doses to thyroid bed remnants and to the whole body can be calculated following the MIRDOSE method-that is, by multiplying the corresponding cumulated activities by the corresponding S factors. Results: The absorbed doses to thyroid bed remnants calculated in this study fall into a very wide range (13-1161 Gy) and showed the highest correlation factors with the following parameters: the absorbed dose rate to thyroid bed remnants, the cumulated activity in thyroid bed remnants, and the maximum radioiodine uptake in thyroid bed remnants. The absorbed doses to the whole body range from 0.12 to 0.23 Gy. The ablation was successful in all patients, and in spite of the wide range of absorbed doses to thyroid bed remnants obtained, no dose-effect correlation could be obtained. Conclusions: Facing DTC treatments from a dosimetric viewpoint in which a predosimetry to calculate the activity of {sup 131}I to be administered is performed is a subject difficult to handle. This statement is based on the fact that although a very wide range of absorbed doses to thyroid bed remnants was obtained (including several absorbed doses well below some dose thresholds previously published to achieve ablation of thyroid bed remnants), ablation of thyroid bed remnants was successful for all patients and therefore no dose-effect correlation could be determined.« less

SU-E-J-127: Real-Time Dosimetric Assessment for Adaptive Head-And-Neck Treatment Via A GPU-Based Deformable Image Registration Framework

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

Qi, S; Neylon, J; Chen, A

2014-06-01

Purposes: To systematically monitor anatomic variations and their dosimetric consequences during head-and-neck (H'N) radiation therapy using a GPU-based deformable image registration (DIR) framework. Methods: Eleven H'N IMRT patients comprised the subject population. The daily megavoltage CT and weekly kVCT scans were acquired for each patient. The pre-treatment CTs were automatically registered with their corresponding planning CT through an in-house GPU-based DIR framework. The deformation of each contoured structure was computed to account for non-rigid change in the patient setup. The Jacobian determinant for the PTVs and critical structures was used to quantify anatomical volume changes. Dose accumulation was performed tomore » determine the actual delivered dose and dose accumulation. A landmark tool was developed to determine the uncertainty in the dose distribution due to registration error. Results: Dramatic interfraction anatomic changes leading to dosimetric variations were observed. During the treatment courses of 6–7 weeks, the parotid gland volumes changed up to 34.7%, the center-of-mass displacement of the two parotids varied in the range of 0.9–8.8mm. Mean doses were within 5% and 3% of the planned mean doses for all PTVs and CTVs, respectively. The cumulative minimum/mean/EUD doses were lower than the planned doses by 18%, 2%, and 7%, respectively for the PTV1. The ratio of the averaged cumulative cord maximum doses to the plan was 1.06±0.15. The cumulative mean doses assessed by the weekly kVCTs were significantly higher than the planned dose for the left-parotid (p=0.03) and right-parotid gland (p=0.006). The computation time was nearly real-time (∼ 45 seconds) for registering each pre-treatment CT to the planning CT and dose accumulation with registration accuracy (for kVCT) at sub-voxel level (<1.5mm). Conclusions: Real-time assessment of anatomic and dosimetric variations is feasible using the GPU-based DIR framework. Clinical implementation of this technology may enable timely plan adaption and potentially lead to improved outcome.« less

Anthracycline-induced cardiotoxicity in patients with paediatric bone sarcoma and soft tissue sarcoma.

PubMed

Bini, Ilaria; Asaftei, Sebastian D; Riggi, Chiara; Tirtei, Elisa; Manicone, Rosaria; Biasin, Eleonora; Basso, Maria Eleonora; Agnoletti, Gabriella; Fagioli, Franca

2017-11-01

Anthracycline cardiotoxicity is an important side-effect in long-term childhood cancer survivors. We evaluated the incidence of and factors associated with anthracycline cardiotoxicity in a population of patients diagnosed with bone or soft tissue sarcoma. Materials and methods We retrospectively enrolled patients diagnosed with bone or soft tissue sarcoma, from 1995 to 2011, treated with anthracycline chemotherapy at our Centre and with a follow-up echocardiography carried out ⩾3 years from cardiotoxic therapy completion. Cardiac toxicity was graded using Common Terminology Criteria for Adverse Events version 4.0. A total of 82 patients were eligible. The median age at treatment was 11.9 years (1.44-18). We evaluated the median cumulative anthracycline dose, age at treatment, sex, thoracic radiotherapy, hematopoietic stem cell transplantation, and high-dose cyclophosphamide treatment as possible risk factors for cardiotoxicity. The median cumulative anthracycline dose was 390.75 mg/m2 (80-580). Of the 82 patients, 12 (14.6%) developed cardiotoxicity with grade ⩾2 ejection fraction decline: four patients were asymptomatic and did not receive any treatment; six patients were treated with pharmacological heart failure therapy; one patient with severe cardiomyopathy underwent heart transplantation and did not need any further treatment; and one patient died while waiting for heart transplantation. The median time at cardiac toxicity, from the end of anthracycline frontline chemotherapy, was 4.2 years (0.05-9.6). Cumulative anthracycline dose ⩾300 mg/m2 (p 0.04) was the only risk factor for cardiotoxicity on statistical analyses. In our population, the cumulative incidence of cardiotoxicity is comparable to rates in the literature. This underlines the need for primary prevention and lifelong cardiac toxicity surveillance programmes in long-term childhood cancer survivors.

Cumulative and antagonistic effects of a mixture of the antiandrogens vinclozolin and iprodione in the pubertal male rat.

PubMed

Blystone, Chad R; Lambright, Christy S; Cardon, Mary C; Furr, Johnathan; Rider, Cynthia V; Hartig, Phillip C; Wilson, Vickie S; Gray, Leon E

2009-09-01

Vinclozolin and iprodione are dicarboximide fungicides that display antiandrogenic effects in the male rat, which suggests that a mixture would lead to cumulative effects on androgen-sensitive end points. Iprodione is a steroid synthesis inhibitor, but androgen receptor antagonist activity, which is displayed by vinclozolin, has not been fully evaluated. Here, we demonstrate that iprodione binds to the human androgen receptor (IC(50) = 86.0 microM), reduces androgen-dependent gene expression, and reduces androgen-sensitive tissue weights in castrated male rats (Hershberger assay). Since vinclozolin and iprodione affect common targets in the pubertal male rat, we tested the hypothesis that a mixture would have cumulative antiandrogenic effects. An iprodione dose, that does not significantly affect androgen-dependent morphological end points, was combined with vinclozolin doses (2 x 5 factorial design). Sprague-Dawley rats were dosed by gavage with vinclozolin at 0, 10, 30, 60, and 100 mg/kg/day with and without 50 mg iprodione/kg/day from postnatal day (PND) 23 to 55-57 (n = 8 per group). The age at puberty (preputial separation [PPS]), organ weights, serum hormones, and ex vivo testis steroid hormone production were measured. Vinclozolin delayed PPS, reduced androgen-sensitive organ weights, and increased serum testosterone. The addition of iprodione enhanced the vinclozolin inhibition of PPS (PND 47.5 vs.49.1; two-way ANOVA: iprodione main effect p = 0.0002). The dose response for several reproductive and nonreproductive organ weights was affected in a cumulative manner. In contrast, iprodione antagonized the vinclozolin-induced increase in serum testosterone. These results demonstrate that these fungicides interact on common targets in a tissue-specific manner when coadministered to the pubertal male rat.

Association of cumulative dose of haloperidol with next-day delirium in older medical ICU patients.

PubMed

Pisani, Margaret A; Araujo, Katy L B; Murphy, Terrence E

2015-05-01

To evaluate the association between cumulative dose of haloperidol and next-day diagnosis of delirium in a cohort of older medical ICU patients, with adjustment for its time-dependent confounding with fentanyl and intubation. Prospective, observational study. Medical ICU at an urban, academic medical center. Age 60 years and older admitted to the medical ICU who received at least one dose of haloperidol (n = 93). Of these, 72 patients were intubated at some point in their medical ICU stay, whereas 21 were never intubated. None. Detailed data were collected concerning time, dosage, route of administration of all medications, as well as for important clinical covariates, and daily status of intubation and delirium using the confusion assessment method for the ICU and a chart-based algorithm. Among nonintubated patients, and after adjustment for time-dependent confounding and important covariates, each additional cumulative milligram of haloperidol was associated with 5% higher odds of next-day delirium with odds ratio of 1.05 (credible interval [CI], 1.02-1.09). After adjustment for time-dependent confounding and covariates, intubation was associated with a five-fold increase in odds of next-day delirium with odds ratio of 5.66 (CI, 2.70-12.02). Cumulative dose of haloperidol among intubated patients did not change their already high likelihood of next-day delirium. After adjustment for time-dependent confounding, the positive associations between indicators of intubation and of cognitive impairment and next-day delirium became stronger. These results emphasize the need for more studies regarding the efficacy of haloperidol for treatment of delirium among older medical ICU patients and demonstrate the value of assessing nonintubated patients.

Assessment of late cardiotoxicity of pirarubicin (THP) in children with acute lymphoblastic leukemia.

PubMed

Shimomura, Yasuto; Baba, Reizo; Watanabe, Arata; Horikoshi, Yasuo; Asami, Keiko; Hyakuna, Nobuyuki; Iwai, Asayuki; Matsushita, Takeshi; Yamaji, Kazutaka; Hori, Toshinori; Tsurusawa, Masahito

2011-09-01

Pirarubicin (tetrahydropyranyl-adriamycin: THP) is a derivative of doxorubicin with reportedly less cardiotoxicity in adults. However no studies of cardiotoxicity in children treated with THP have been reported. This study was performed to assess the THP-induced cardiotoxicity for children with acute lymphoblastic leukemia (ALL). This study comprised 61 asymptomatic patients aged from 7.6 to 25.7 years old. Median follow-up time after completion of anthracycline treatment was 8.1 years (range: 1.7-12.5). The cumulative dose of THP ranged from 120 to 740 mg/m(2) with a median of 180 mg/m(2) . Patients underwent electrocardiogram (ECG), echocardiography, the 6-min walk test (6MWT), and measurements of serum brain natriuretic peptide (BNP) before and after exercise. All subjects showed normal left ventricular function assessed by echocardiography. Ventricular premature contraction in Holter ECG and reduced exercise tolerance in the 6MWT were detected in 2/46 (3.3%) and 5/41(12.2%), respectively. Abnormal BNP levels were detected in 6/60 (10%) both before and after exercise. The cumulative dose of THP was significantly correlated with BNP levels after exercise (r = 0.27, P = 0.03), but not with any other cardiac measurements. Further analysis revealed that subjects with a high cumulative dose ≧300 mg/m(2) had significantly higher BNP levels after exercise compared with subjects with a low cumulative dose <300 mg/m(2) (P = 0.04). No significant cardiac dysfunction was detected in long-term survivors who received THP treatment. The use of post-exercise BNP level to indicate high cardiotoxicity risk should be verified by further study. Copyright © 2011 Wiley-Liss, Inc.

Radiation risks in lung cancer screening programs: a comparison with nuclear industry workers and atomic bomb survivors.

PubMed

McCunney, Robert J; Li, Jessica

2014-03-01

The National Lung Cancer Screening Trial (NLST) demonstrated that screening with low-dose CT (LDCT) scan reduced lung cancer and overall mortality by 20% and 7%, respectively. The LDCT scanning involves an approximate 2-mSv dose, whereas full-chest CT scanning, the major diagnostic study used to follow up nodules, may involve a dose of 8 mSv. Radiation associated with CT scanning and other diagnostic studies to follow up nodules may present an independent risk of lung cancer. On the basis of the NLST, we estimated the incidence and prevalence of nodules detected in screening programs. We followed the Fleischner guidelines for follow-up of nodules to assess cumulative radiation exposure over 20- and 30-year periods. We then evaluated nuclear worker cohort studies and atomic bomb survivor studies to assess the risk of lung cancer from radiation associated with long-term lung cancer screening programs. The findings indicate that a 55-year-old lung screening participant may experience a cumulative radiation exposure of up to 280 mSv over a 20-year period and 420 mSv over 30 years. These exposures exceed those of nuclear workers and atomic bomb survivors. This assessment suggests that long-term (20-30 years) LDCT screening programs are associated with nontrivial cumulative radiation doses. Current lung cancer screening protocols, if conducted over 20- to 30-year periods, can independently increase the risk of lung cancer beyond cigarette smoking as a result of cumulative radiation exposure. Radiation exposures from LDCT screening and follow-up diagnostic procedures exceed lifetime radiation exposures among nuclear power workers and atomic bomb survivors.

Safety of multiple stereotactic radiosurgery treatments for multiple brain lesions.

PubMed

Hillard, Virany H; Shih, Lynn L; Chin, Shing; Moorthy, Chitti R; Benzil, Deborah L

2003-07-01

Stereotactic radiosurgery (SRS) is a widely used therapy for multiple brain lesions, and studies have clearly established the safety and efficacy of single-dose SRS. However, as patient survival has increased, the recurrence of tumors and the development of metastases to new sites within the brain have made it desirable to repeat treatments over time. The cumulative toxicity of multi-isocenter, multiple treatments has not been well defined. We have retrospectively studied 10 patients who received multiple SRS treatments for multiple brain lesions to assess the cumulative toxicity of these treatments. In a retrospective review of all patients treated with SRS using the X-knife (Radionics, Burlington, MA) at Westchester Medical Center/New York Medical College between December 1995 and December 2000, 10 patients were identified who received at least two treatments to at least 3 isocenters and had a minimum follow-up period of 6 months. Image fusion technique was used to determine cumulative doses to targeted lesions, whole brain and critical brain structures. Toxicities and complications were identified by chart and radiological review. The average of the maximum doses (cGy) to a point within the whole brain was 2402 (range 1617-3953); to the brainstem, 1059 (range 48-4126); to the right optic nerve, 223 (range 14-1012); to the left optic nerve, 159 (range 17-475); and to the optic chiasm, 219 (range 15-909). There were no focal neurological toxicities, including visual disturbances, cranial nerve palsies, or ataxia in any of the 10 patients. There were also no global toxicities, including cognitive decline or secondary tumors. Only one patient developed seizures that were difficult to control in association with radiation necrosis. Multiple SRS treatments at the cumulative doses used in our study are a safe therapy for patients with multiple brain lesions.

Curvilinear bodies are associated with adverse effects on muscle function but not with hydroxychloroquine dosing.

PubMed

Khoo, Thomas; Otto, Sophia; Smith, Caroline; Koszyca, Barbara; Lester, Sue; Blumbergs, Peter; Limaye, Vidya

2017-03-01

The clinical significance of curvilinear bodies (CB) seen in association with hydroxychloroquine (HCQ) therapy is uncertain. Patients with CB on muscle biopsy performed between 2006 and the present were identified, and their clinical features including body mass index and cumulative HCQ dose were recorded. A control group of 16 patients with idiopathic inflammatory myositis (IIM) on HCQ at time of biopsy but without evidence of CB was identified. Nineteen patients with CB were identified; details were available for 18. Among patients with CB, 7/18 also had IIM. Seven out of ten patients with CB who did not have IIM or MHCI/II expression had proximal weakness; 7/11 had raised serum creatinine kinase (CK) levels. There was no difference in body weight (p = 0.47), body mass index (p = 0.93), cumulative HCQ dose (p = 0.52) or cumulative dose adjusted for body weight (p = 0.39) or body mass index (p = 0.32) between patients with CB and controls. Patients with CB had lower median CK levels than controls (p = 0.034). Weakness was present in 12/17 patients and 12/16 controls (p = 1.0). Concurrent proton-pump inhibitors were co-prescribed in 12/18 (67 %) patients with CB and in 6/16 (38 %) controls (p = 0.17). Development of CB does not appear to be related to cumulative HCQ dose or body weight. Patients with CB frequently have muscle weakness in the absence of MHC1 expression suggesting a role for non-immune mechanisms of muscle injury. A high proportion of patients with CB are co-prescribed proton-pump inhibitors raising the possibility that co-prescription of both agents may disrupt lysosomal function and adversely affect muscle function.

Ketorolac use may increase risk of postoperative pancreatic fistula after pancreaticoduodenectomy.

PubMed

Kowalsky, Stacy J; Zenati, Mazen S; Steve, Jennifer; Lee, Kenneth K; Hogg, Melissa E; Zeh, Herbert J; Zureikat, Amer H

2018-01-01

Ketorolac (Toradol), a commonly used nonselective nonsteroidal anti-inflammatory drug (NSAID) in the postoperative period, has been associated with increased risk of anastomotic leak after colon resection. The effect of postoperative NSAID and ketorolac use on postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) is unknown. Retrospective review of consecutive PDs at a high-volume pancreas center from 2012 to 2015. POPF was identified and graded using International Study Group on Pancreatic Fistula criteria. Demographics, operative variables and 30-d postoperative NSAID use, dosage, and timing (early = postoperative day [POD] 0-5, late > POD 5) were collected. Univariate and multivariate logistic regressions were used to identify predictors of POPF. Four hundred twenty-three PDs were analyzed (mean age 66 y, 47% female), and 60% received NSAIDs postoperatively. Ketorolac (median POD 0-5 cumulative dose = 90 mg, interquartile range 60-165) was used in 35.7% (n = 151). POPF occurred in 90 patients (21.3%). Early (POD 0-5) ketorolac use was associated with increased POPF, especially grade A (odds ratio [OR] 2.16, P = 0.036). Each 25 mg incremental increase in ketorolac use was associated with a 10% increase in the incidence of POPF (OR 1.10, P = 0.021), whereas a cumulative dose of >150 mg was associated with a 44% increased risk of POPF (OR 1.44, 95% confidence interval 1.03-2.01, P = 0.035). A multivariate regression model identified estimated blood loss, soft gland, pancreatic duct diameter, body mass index, and cumulative ketorolac dose >150 mg as independent predictors of POPF (P < 0.0001, pseudo R 2  = 0.149). Increasing doses of ketorolac in the early postoperative period are associated with increased risk of POPF, whereas a cumulative dose of >150 mg is an independent predictor of POPF after PD. Copyright © 2017 Elsevier Inc. All rights reserved.

Fetal radiation monitoring and dose minimization during intensity modulated radiation therapy for glioblastoma in pregnancy.

PubMed

Horowitz, David P; Wang, Tony J C; Wuu, Cheng-Shie; Feng, Wenzheng; Drassinower, Daphnie; Lasala, Anita; Pieniazek, Radoslaw; Cheng, Simon; Connolly, Eileen P; Lassman, Andrew B

2014-11-01

We examined the fetal dose from irradiation of glioblastoma during pregnancy using intensity modulated radiation therapy (IMRT), and describe fetal dose minimization using mobile shielding devices. A case report is described of a pregnant woman with glioblastoma who was treated during the third trimester of gestation with 60 Gy of radiation delivered via a 6 MV photon IMRT plan. Fetal dose without shielding was estimated using an anthropomorphic phantom with ion chamber and diode measurements. Clinical fetal dose with shielding was determined with optically stimulated luminescent dosimeters and ion chamber. Clinical target volume (CTV) and planning target volume (PTV) coverage was 100 and 98 % receiving 95 % of the prescription dose, respectively. Normal tissue tolerances were kept below quantitative analysis of normal tissue effects in the clinic (QUANTEC) recommendations. Without shielding, anthropomorphic phantom measurements showed a cumulative fetal dose of 0.024 Gy. In vivo measurements with shielding in place demonstrated a cumulative fetal dose of 0.016 Gy. The fetal dose estimated without shielding was 0.04 % and with shielding was 0.026 % of the target dose. In vivo estimation of dose equivalent received by the fetus was 24.21 mSv. Using modern techniques, brain irradiation can be delivered to pregnant patients in the third trimester with very low measured doses to the fetus, without compromising target coverage or normal tissue dose constraints. Fetal dose can further be reduced with the use of shielding devices, in keeping with the principle of as low as reasonably achievable.

An application of the Aggregate Exposure Pathway (AEP) and Adverse Outcome Pathway (AOP) frameworks to mechanistically integrate data sources across multiple species into cumulative risk assessment (CRA)

EPA Science Inventory

Toxicologists use dose-response data from both in vivo and in vitro experiments to evaluate the effects of chemical contaminants on organisms. Cumulative risk assessments (CRAs) consider the effects of multiple stressors on multiple endpoints, and utilize environmental exposure ...

Measurements of long-term external and internal radiation exposure of inhabitants of some villages of the Bryansk region of Russia after the Chernobyl accident.

PubMed

Bernhardsson, C; Zvonova, I; Rääf, C; Mattsson, S

2011-10-15

A Nordic-Soviet programme was initiated in 1990 to evaluate the external and internal radiation exposure of the inhabitants of several villages in the Bryansk region of Russia. This area was one of the number of areas particularly affected by the nuclear accident at the Chernobyl Nuclear Power Plant in 1986. Measurements were carried out yearly until 1998 and after that more irregularly; in 2000, 2006 and 2008 respectively. The effective dose estimates were based on individual thermoluminescent dosemeters and on in vivo measurements of the whole body content of (137)Cs (and (134)Cs during the first years of the programme). The decrease in total effective dose during the almost 2 decade follow-up was due to a continuous decrease in the dominating external exposure and a less decreasing but highly variable exposure from internal irradiation. In 2008, the observed average effective dose (i.e. the sum of external and internal exposure) from Chernobyl (137)Cs to the residents was estimated to be 0.3mSv y(-1). This corresponds to 8% of the estimated annual dose in 1990 and to 1% of the estimated annual dose in 1986. As a mean for the population group and for the period of the present study (2006-2008), the average yearly effective dose from Chernobyl cesium was comparable to the absorbed dose obtained annually from external exposure to cosmic radiation plus internal exposure to naturally occurring radionuclides in the human body. Our data indicate that the effective dose from internal exposure is becoming increasingly important as the body burdens of Chernobyl (137)Cs are decreasing more slowly than the external exposure. However, over the years there have been large individual variations in both the external and internal effective doses, as well as differences between the villages investigated. These variations and differences are presented and discussed in this paper. Copyright © 2011 Elsevier B.V. All rights reserved.

Describing Treatment Intensity in Milieu Teaching Interventions for Children with Developmental Disabilities: A Review

ERIC Educational Resources Information Center

Parker-McGowan, Quannah; Chen, Mo; Reichle, Joe; Pandit, Shivani; Johnson, LeAnne; Kreibich, Shelley

2014-01-01

Purpose: This investigation aimed to apply the dosage framework proposed by Warren, Fey, and Yoder (2007) to variations of milieu language teaching intervention strategies to explore how each of the dosage parameters (i.e., dose, dose form, dose frequency, total duration, and cumulative intervention intensity) was reported in the located…

EPA's SHEDS-multimedia model: children's cumulative pyrethroid exposure estimates and evaluation against NHANES biomarker data.

PubMed

Xue, Jianping; Zartarian, Valerie; Tornero-Velez, Rogelio; Tulve, Nicolle S

2014-12-01

The U.S. EPA's SHEDS-Multimedia model was applied to enhance the understanding of children's exposures and doses to multiple pyrethroid pesticides, including major contributing chemicals and pathways. This paper presents combined dietary and residential exposure estimates and cumulative doses for seven commonly used pyrethroids, and comparisons of model evaluation results with NHANES biomarker data for 3-PBA and DCCA metabolites. Model input distributions were fit to publicly available pesticide usage survey data, NHANES, and other studies, then SHEDS-Multimedia was applied to estimate total pyrethroid exposures and doses for 3-5 year olds for one year variability simulations. For dose estimations we used a pharmacokinetic model and two approaches for simulating dermal absorption. SHEDS-Multimedia predictions compared well to NHANES biomarker data: ratios of 3-PBA observed data to SHEDS-Multimedia modeled results were 0.88, 0.51, 0.54 and 1.02 for mean, median, 95th, and 99th percentiles, respectively; for DCCA, the ratios were 0.82, 0.53, 0.56, and 0.94. Modeled time-averaged cumulative absorbed dose of the seven pyrethroids was 3.1 nmol/day (versus 8.4 nmol/day for adults) in the general population (residential pyrethroid use and non-use homes) and 6.7 nmol/day (versus 10.5 nmol/day for adults) in the simulated residential pyrethroid use population. For the general population, contributions to modeled cumulative dose by chemical were permethrin (60%), cypermethrin (22%), and cyfluthrin (16%); for residential use homes, contributions were cypermethrin (49%), permethrin (29%), and cyfluthrin (17%). The primary exposure route for 3-5 year olds in the simulated residential use population was non-dietary ingestion exposure; whereas for the simulated general population, dietary exposure was the primary exposure route. Below the 95th percentile, the major exposure pathway was dietary for the general population; non-dietary ingestion was the major pathway starting below the 70th percentile for the residential use population. The new dermal absorption methodology considering surface loading had some impact, but did not change the order of key pathways. Published by Elsevier Ltd.

SU-C-18C-06: Radiation Dose Reduction in Body Interventional Radiology: Clinical Results Utilizing a New Imaging Acquisition and Processing Platform

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

Kohlbrenner, R; Kolli, KP; Taylor, A

2014-06-01

Purpose: To quantify the patient radiation dose reduction achieved during transarterial chemoembolization (TACE) procedures performed in a body interventional radiology suite equipped with the Philips Allura Clarity imaging acquisition and processing platform, compared to TACE procedures performed in the same suite equipped with the Philips Allura Xper platform. Methods: Total fluoroscopy time, cumulative dose area product, and cumulative air kerma were recorded for the first 25 TACE procedures performed to treat hepatocellular carcinoma (HCC) in a Philips body interventional radiology suite equipped with Philips Allura Clarity. The same data were collected for the prior 85 TACE procedures performed to treatmore » HCC in the same suite equipped with Philips Allura Xper. Mean values from these cohorts were compared using two-tailed t tests. Results: Following installation of the Philips Allura Clarity platform, a 42.8% reduction in mean cumulative dose area product (3033.2 versus 1733.6 mGycm∧2, p < 0.0001) and a 31.2% reduction in mean cumulative air kerma (1445.4 versus 994.2 mGy, p < 0.001) was achieved compared to similar procedures performed in the same suite equipped with the Philips Allura Xper platform. Mean total fluoroscopy time was not significantly different between the two cohorts (1679.3 versus 1791.3 seconds, p = 0.41). Conclusion: This study demonstrates a significant patient radiation dose reduction during TACE procedures performed to treat HCC after a body interventional radiology suite was converted to the Philips Allura Clarity platform from the Philips Allura Xper platform. Future work will focus on evaluation of patient dose reduction in a larger cohort of patients across a broader range of procedures and in specific populations, including obese patients and pediatric patients, and comparison of image quality between the two platforms. Funding for this study was provided by Philips Healthcare, with 5% salary support provided to authors K. Pallav Kolli and Robert G. Gould for time devoted to the study. Data acquisition and analysis was performed by the authors independent of the funding source.« less

Markov model of the loan portfolio dynamics considering influence of management and external economic factors

NASA Astrophysics Data System (ADS)

Bozhalkina, Yana; Timofeeva, Galina

2016-12-01

Mathematical model of loan portfolio in the form of a controlled Markov chain with discrete time is considered. It is assumed that coefficients of migration matrix depend on corrective actions and external factors. Corrective actions include process of receiving applications, interaction with existing solvent and insolvent clients. External factors are macroeconomic indicators, such as inflation and unemployment rates, exchange rates, consumer price indices, etc. Changes in corrective actions adjust the intensity of transitions in the migration matrix. The mathematical model for forecasting the credit portfolio structure taking into account a cumulative impact of internal and external changes is obtained.

Hydrogen peroxide induced by the fungicide prothioconazole triggers deoxynivalenol (DON) production by Fusarium graminearum

PubMed Central

2010-01-01

Background Fusarium head blight is a very important disease of small grain cereals with F. graminearum as one of the most important causal agents. It not only causes reduction in yield and quality but from a human and animal healthcare point of view, it produces mycotoxins such as deoxynivalenol (DON) which can accumulate to toxic levels. Little is known about external triggers influencing DON production. Results In the present work, a combined in vivo/in vitro approach was used to test the effect of sub lethal fungicide treatments on DON production. Using a dilution series of prothioconazole, azoxystrobin and prothioconazole + fluoxastrobin, we demonstrated that sub lethal doses of prothioconazole coincide with an increase in DON production 48 h after fungicide treatment. In an artificial infection trial using wheat plants, the in vitro results of increased DON levels upon sub lethal prothioconazole application were confirmed illustrating the significance of these results from a practical point of view. In addition, further in vitro experiments revealed a timely hyperinduction of H2O2 production as fast as 4 h after amending cultures with prothioconazole. When applying H2O2 directly to germinating conidia, a similar induction of DON-production by F. graminearum was observed. The effect of sub lethal prothioconazole concentrations on DON production completely disappeared when applying catalase together with the fungicide. Conclusions These cumulative results suggest that H2O2 induced by sub lethal doses of the triazole fungicide prothioconazole acts as a trigger of DON biosynthesis. In a broader framework, this work clearly shows that DON production by the plant pathogen F. graminearum is the result of the interaction of fungal genomics and external environmental triggers. PMID:20398299

End-stage renal disease after occupational lead exposure: 20 years of follow-up.

PubMed

Evans, Marie; Discacciati, Andrea; Quershi, Abdul Rashid; Åkesson, Agneta; Elinder, Carl-Gustaf

2017-06-01

Whether low-level exposure to lead may give rise to chronic kidney disease or end-stage renal disease (ESRD) is debated. In this study, we aimed to specifically investigate if low-level occupational exposure to lead was associated with increased incidence of ESRD. The incidence of starting renal replacement therapy as a result of ESRD was examined in a cohort of10 303 lead-workers who had controlled blood lead concentrations due to a compulsory occupational health surveillance programme in Sweden during the time period 1977-1990. The ESRD incidence (obtained through register-linkage) among the lead-exposed workers was compared with the age, sex and calendar period-adjusted expected incidence based on data from the Swedish renal registry. Dose-response association was evaluated in external (general population) and internal (within the occupational cohort) comparisons by highest achieved blood lead level. There were 30 (0.29%) individuals in the cohort who developed ESRD during the median follow-up period of 26.3 years. The standardised incidence ratio (SIR) for ESRD incidence was 0.79 (95% CI 0.54 to 1.13). Among those who achieved the highest blood lead (>41.4 µg/dL), the SIR was 1.01 (0.44 to 1.99). There was no evidence of a dose-response relationship between the maximum achieved blood lead or the cumulative blood lead exposure and ESRD in external or internal comparisons. This study of workers with documented occupational lead exposures followed for 20 years shows no statistically significant association between lead exposure (following the current occupational recommendations for Sweden) and ESRD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Microdose Induced Drain Leakage Effects in Power Trench MOSFETs: Experiment and Modeling

NASA Astrophysics Data System (ADS)

Zebrev, Gennady I.; Vatuev, Alexander S.; Useinov, Rustem G.; Emeliyanov, Vladimir V.; Anashin, Vasily S.; Gorbunov, Maxim S.; Turin, Valentin O.; Yesenkov, Kirill A.

2014-08-01

We study experimentally and theoretically the micro-dose induced drain-source leakage current in the trench power MOSFETs under irradiation with high-LET heavy ions. We found experimentally that cumulative increase of leakage current occurs by means of stochastic spikes corresponding to a strike of single heavy ion into the MOSFET gate oxide. We simulate this effect with the proposed analytic model allowing to describe (including Monte Carlo methods) both the deterministic (cumulative dose) and stochastic (single event) aspects of the problem. Based on this model the survival probability assessment in space heavy ion environment with high LETs was proposed.

Analysis of computed tomography density of liver before and after amiodarone administration.

PubMed

Matsuda, Masazumi; Otaka, Aoi; Tozawa, Tomoki; Asano, Tomoyuki; Ishiyama, Koichi; Hashimoto, Manabu

2018-05-01

To evaluate CT density of liver changes between before and after amiodarone administration. Twenty-five patients underwent non-enhanced CT including the liver before and after amiodarone administration. We set regions of interest (ROIs) at liver S8, spleen, paraspinal muscle, and calculated average CT density in these ROIs, then compared CT density between liver and other organs. Statistical differences between CT density of liver and various ratios before and after administration were determined, along with correlations between cumulative dose of amiodarone and liver density after administration, density change of liver, and various ratios after administration. Liver density, liver-to-spleen ratio, and liver-to-paraspinal muscle ratio differed significantly between before and after amiodarone administration. No significant correlations were found between cumulative doses of amiodarone and any of liver density after administration, density change of liver, or various ratios after administration. CT density of liver after amiodarone administration was significantly higher than that before administration. No correlations were identified between cumulative dose of amiodarone and either liver density after administration or density change of liver. Amiodarone usage should be checked when radiologists identify high density of the liver on CT.

Toward an ozone standard to protect vegetation based on effective dose: A review of deposition resistances and a possible metric

Treesearch

W. J. Massman

2004-01-01

Present air quality standards to protect vegetation from ozone are based on measured concentrations (i.e., exposure) rather than on plant uptake rates (or dose). Some familiar cumulative exposure-based indices include SUM06, AOT40, and W126. However, plant injury is more closely related to dose, or more appropriately to effective dose, than to exposure. This study...

The Study of External Dose Rate and Retained Body Activity of Patients Receiving 131I Therapy for Differentiated Thyroid Carcinoma

PubMed Central

Zhang, Haiying; Jiao, Ling; Cui, Songye; Wang, Liang; Tan, Jian; Zhang, Guizhi; He, Yajing; Ruan, Shuzhou; Fan, Saijun; Zhang, Wenyi

2014-01-01

Radiation safety is an integral part of targeted radionuclide therapy. The aim of this work was to study the external dose rate and retained body activity as functions of time in differentiated thyroid carcinoma patients receiving 131I therapy. Seventy patients were stratified into two groups: the ablation group (A) and the follow-up group (FU). The patients’ external dose rate was measured, and simultaneously, their retained body radiation activity was monitored at various time points. The equations of the external dose rate and the retained body activity, described as a function of hours post administration, were fitted. Additionally, the release time for patients was calculated. The reduction in activity in the group receiving a second or subsequent treatment was more rapid than the group receiving only the initial treatment. Most important, an expeditious method was established to indirectly evaluate the retained body activity of patients by measuring the external dose rate with a portable radiation survey meter. By this method, the calculated external dose rate limits are 19.2, 8.85, 5.08 and 2.32 μSv·h−1 at 1, 1.5, 2 and 3 m, respectively, according to a patient’s released threshold level of retained body activity <400 MBq. This study is beneficial for radiation safety decision-making. PMID:25337944

Error detection capability of a novel transmission detector: a validation study for online VMAT monitoring.

PubMed

Pasler, Marlies; Michel, Kilian; Marrazzo, Livia; Obenland, Michael; Pallotta, Stefania; Björnsgard, Mari; Lutterbach, Johannes

2017-09-01

The purpose of this study was to characterize a new single large-area ionization chamber, the integral quality monitor system (iRT, Germany), for online and real-time beam monitoring. Signal stability, monitor unit (MU) linearity and dose rate dependence were investigated for static and arc deliveries and compared to independent ionization chamber measurements. The dose verification capability of the transmission detector system was evaluated by comparing calculated and measured detector signals for 15 volumetric modulated arc therapy plans. The error detection sensitivity was tested by introducing MLC position and linac output errors. Deviations in dose distributions between the original and error-induced plans were compared in terms of detector signal deviation, dose-volume histogram (DVH) metrics and 2D γ-evaluation (2%/2 mm and 3%/3 mm). The detector signal is linearly dependent on linac output and shows negligible (<0.4%) dose rate dependence up to 460 MU min -1 . Signal stability is within 1% for cumulative detector output; substantial variations were observed for the segment-by-segment signal. Calculated versus measured cumulative signal deviations ranged from  -0.16%-2.25%. DVH, mean 2D γ-value and detector signal evaluations showed increasing deviations with regard to the respective reference with growing MLC and dose output errors; good correlation between DVH metrics and detector signal deviation was found (e.g. PTV D mean : R 2   =  0.97). Positional MLC errors of 1 mm and errors in linac output of 2% were identified with the transmission detector system. The extensive tests performed in this investigation show that the new transmission detector provides a stable and sensitive cumulative signal output and is suitable for beam monitoring during patient treatment.

Synergistic Effects of Incubation in Rotating Bioreactors and Cumulative Low Dose 60Co γ-ray Irradiation on Human Immortal Lymphoblastoid Cells

NASA Astrophysics Data System (ADS)

Wei, Lijun; Han, Fang; Yue, Lei; Zheng, Hongxia; Yu, Dan; Ma, Xiaohuan; Cheng, Huifang; Li, Yu

2012-11-01

The complex space environments can influence cell structure and function. The research results on space biology have shown that the major mutagenic factors in space are microgravity and ionizing radiation. In addition, possible synergistic effects of radiation and microgravity on human cells are not well understood. In this study, human immortal lymphoblastoid cells were established from human peripheral blood lymphocytes and the cells were treated with low dose (0.1, 0.15 and 0.2 Gy) cumulative 60Co γ-irradiation and simulated weightlessness [obtained by culturing cells in the Rotating Cell Culture System (RCCS)]. The commonly used indexes of cell damage such as micronucleus rate, cell cycle and mitotic index were studied. Previous work has proved that Gadd45 (growth arrest and DNA-damage-inducible protein 45) gene increases with a dose-effect relationship, and will possibly be a new biological dosimeter to show irradiation damage. So Gadd45 expression is also detected in this study. The micronucleus rate and the expression of Gadd45α gene increased with irradiation dose and were much higher after incubation in the rotating bioreactor than that in the static irradiation group, while the cell proliferation after incubation in the rotating bioreactor decreased at the same time. These results indicate synergetic effects of simulated weightlessness and low dose irradiation in human cells. The cell damage inflicted by γ-irradiation increased under simulated weightlessness. Our results suggest that during medium- and long-term flight, the human body can be damaged by cumulative low dose radiation, and the damage will even be increased by microgravity in space.

Quantifying public radiation exposure related to lutetium-177 octreotate therapy for the development of a safe outpatient treatment protocol.

PubMed

Olmstead, Craig; Cruz, Kyle; Stodilka, Robert; Zabel, Pamela; Wolfson, Robert

2015-02-01

Radionuclide therapies, including treatment of neuroendocrine tumors with lutetium-177 (Lu-177) octreotate, often involve hospital admission to minimize radiation exposure to the public. Overnight admission due to Lu-177 octreotate therapy incurs additional cost for the hospital and is an inconvenience for the patient. This study endeavors to characterize the potential radiation risk to caregivers and the public should Lu-177 octreotate therapies be performed on an outpatient basis. Dose rate measurements of radiation emanating from 10 patients were taken 30 min, 4, and 20 h after initiation of Lu-177 octreotate therapy. Instadose radiation dose measurement monitors were also placed around the patients' rooms to assess the potential cumulative radiation exposure during the initial 30 min-4 h after treatment (simulating the hospital-based component of the outpatient model) as well as 4-20 h after treatment (simulating the discharged outpatient portion). The mean recorded dose rate at 30 min, 4, and 20 h after therapy was 20.4, 14.0, and 6.6 μSv/h, respectively. The majority of the cumulative dose readings were below the minimum recordable threshold of 0.03 mSv, with a maximum dose recorded of 0.18 mSv. Given the low dose rate and cumulative levels of radiation measured, the results support that an outpatient Lu-177 octreotate treatment protocol would not jeopardize public safety. Nevertheless, the concept of ALARA still requires that detailed radiation safety protocols be developed for Lu-177 octreotate outpatients to minimize radiation exposure to family members, caregivers, and the general public.

Error detection capability of a novel transmission detector: a validation study for online VMAT monitoring

NASA Astrophysics Data System (ADS)

Pasler, Marlies; Michel, Kilian; Marrazzo, Livia; Obenland, Michael; Pallotta, Stefania; Björnsgard, Mari; Lutterbach, Johannes

2017-09-01

The purpose of this study was to characterize a new single large-area ionization chamber, the integral quality monitor system (iRT, Germany), for online and real-time beam monitoring. Signal stability, monitor unit (MU) linearity and dose rate dependence were investigated for static and arc deliveries and compared to independent ionization chamber measurements. The dose verification capability of the transmission detector system was evaluated by comparing calculated and measured detector signals for 15 volumetric modulated arc therapy plans. The error detection sensitivity was tested by introducing MLC position and linac output errors. Deviations in dose distributions between the original and error-induced plans were compared in terms of detector signal deviation, dose-volume histogram (DVH) metrics and 2D γ-evaluation (2%/2 mm and 3%/3 mm). The detector signal is linearly dependent on linac output and shows negligible (<0.4%) dose rate dependence up to 460 MU min-1. Signal stability is within 1% for cumulative detector output; substantial variations were observed for the segment-by-segment signal. Calculated versus measured cumulative signal deviations ranged from  -0.16%-2.25%. DVH, mean 2D γ-value and detector signal evaluations showed increasing deviations with regard to the respective reference with growing MLC and dose output errors; good correlation between DVH metrics and detector signal deviation was found (e.g. PTV D mean: R 2  =  0.97). Positional MLC errors of 1 mm and errors in linac output of 2% were identified with the transmission detector system. The extensive tests performed in this investigation show that the new transmission detector provides a stable and sensitive cumulative signal output and is suitable for beam monitoring during patient treatment.

Radiation dose to critical body organs for October 1989 proton event

NASA Technical Reports Server (NTRS)

Simonsen, Lisa C.; Atwell, William; Nealy, John E.; Cucinotta, Francis A.

1992-01-01

The Geostationary Operational Environmental Satellite (GOES-7) provides high-quality environmental data about the temporal development and energy characteristics of the protons emitted during a solar particle event. The GOES-7 time history of the hourly averaged integral proton flux for various particle kinetic energies are analyzed for the solar proton event occurring October 19-29, 1989. This event is similar to the August 1972 event that has been widely studied to estimate free-space and planetary radiation-protection requirements. By analyzing the time-history data, the dose rates, which can vary over many orders of magnitude in the early phases of the flare, can be estimated as well as the cumulative dose as a function of time. When basic transport results are coupled with detailed body organ thickness distributions calculated with the Computerized Anatomical Man and Computerized Anatomical Female models, the dose rates and cumulative doses to specific organs can be predicted. With these results, the risks of cancer incidence and mortality are estimated for astronauts in free space protected by various water shield thicknesses.

Staff Radiation Doses in a Real-Time Display Inside the Angiography Room

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

Sanchez, Roberto, E-mail: rmsanchez.hcsc@salud.madrid.org; Vano, E.; Fernandez, J. M.

MethodsThe evaluation of a new occupational Dose Aware System (DAS) showing staff radiation doses in real time has been carried out in several angiography rooms in our hospital. The system uses electronic solid-state detectors with high-capacity memory storage. Every second, it archives the dose and dose rate measured and is wirelessly linked to a base-station screen mounted close to the diagnostic monitors. An easy transfer of the values to a data sheet permits further analysis of the scatter dose profile measured during the procedure, compares it with patient doses, and seeks to find the most effective actions to reduce operatormore » exposure to radiation.ResultsThe cumulative occupational doses measured per procedure (shoulder-over lead apron) ranged from 0.6 to 350 {mu}Sv when the ceiling-suspended screen was used, and DSA (Digital Subtraction Acquisition) runs were acquired while the personnel left the angiography room. When the suspended screen was not used and radiologists remained inside the angiography room during DSA acquisitions, the dose rates registered at the operator's position reached up to 1-5 mSv/h during fluoroscopy and 12-235 mSv/h during DSA acquisitions. In such case, the cumulative scatter dose could be more than 3 mSv per procedure.ConclusionReal-time display of doses to staff members warns interventionists whenever the scatter dose rates are too high or the radiation protection tools are not being properly used, providing an opportunity to improve personal protection accordingly.« less

Long-Term Outcomes Among Adult Survivors of Childhood Central Nervous System Malignancies in the Childhood Cancer Survivor Study

PubMed Central

Liu, Qi; Yasui, Yutaka; Huang, Sujuan; Ness, Kirsten K.; Leisenring, Wendy; Hudson, Melissa M.; Donaldson, Sarah S.; King, Allison A.; Stovall, Marilyn; Krull, Kevin R.; Robison, Leslie L.; Packer, Roger J.

2009-01-01

Background Adult survivors of childhood central nervous system (CNS) malignancies are at high risk for long-term morbidity and late mortality. However, patterns of late mortality, the long-term risks of subsequent neoplasms and debilitating medical conditions, and sociodemographic outcomes have not been comprehensively characterized for individual diagnostic and treatment groups. Methods We collected information on treatment, mortality, chronic medical conditions, and neurocognitive functioning of adult 5-year survivors of CNS malignancies diagnosed between 1970 and 1986 within the Childhood Cancer Survivor Study. Using competing risk framework, we calculated cumulative mortality according to cause of death and cumulative incidence of subsequent neoplasms according to exposure and dose of cranial radiation therapy (RT). Neurocognitive impairment and socioeconomic outcomes were assessed with respect to dose of CNS radiotherapy to specific brain regions. Cumulative incidence of chronic medical conditions was compared between survivors and siblings using Cox regression models. All tests of statistical significance were two-sided. Results Among all eligible 5-year survivors (n = 2821), cumulative late mortality at 30 years was 25.8% (95% confidence interval [CI] = 23.4% to 28.3%), due primarily to recurrence and/or progression of primary disease. Patients who received cranial RT of 50 Gy or more (n = 813) had a cumulative incidence of a subsequent neoplasm within the CNS of 7.1% (95% CI = 4.5% to 9.6%) at 25 years from diagnosis compared with 1.0% (95% CI = 0% to 2.3%) for patients who had no RT. Survivors had higher risk than siblings of developing new endocrine, neurological, or sensory complications 5 or more years after diagnosis. Neurocognitive impairment was high and proportional to radiation dose for specific tumor types. There was a dose-dependent association between RT to the frontal and/or temporal lobes and lower rates of employment, and marriage. Conclusions Survivors of childhood CNS malignancies are at high risk for late mortality and for developing subsequent neoplasms and chronic medical conditions. Care providers should be informed of these risks so they can provide risk-directed care and develop screening guidelines. PMID:19535780

A possible early sign of hydroxychloroquine macular toxicity.

PubMed

Brandao, Livia M; Palmowski-Wolfe, Anja M

2016-02-01

Hydroxychloroquine (HCQ) has a low risk of retinal toxicity which increases dramatically with a cumulative dose of >1000 g. Here we report a case of HCQ macular toxicity presentation in a young patient with a cumulative dose of 438 g. A 15-year-old female started attending annual consultations for retinal toxicity screening in our clinic after 3 years of HCQ treatment for juvenile idiopathic dermatomyositis. She had been diagnosed at age 12 and had been on hydroxychloroquine 200 mg/day, cyclosporin 150 mg/day and vitamin D3 since. Screening consultations included: complete ophthalmologic examination, automated perimetry (AP, M Standard, Octopus 101, Haag-Streit), multifocal electroretinogram (VERIS 6.06™, FMSIII), optical coherence tomography (OCT, fast macular protocol, Cirrus SD-OCT, Carl Zeiss), fundus autofluorescence imaging (Spectralis OCT, Heidelberg Engineering Inc.) and color testing (Farnsworth-Panel-D-15). After 5 years of treatment, AP demonstrated reduced sensibility in only one extra-foveal point in each eye (p < 0.2). Even though other exams showed no alteration and the cumulative dose was only around 353 g, consultations were increased to every 6 months. After 2-year follow-up, that is, 7 years of HCQ, a bilateral paracentral macula thinning was evident on OCT, suggestive of bull's eye maculopathy. However, the retinal pigmented epithelium appeared intact and AP was completely normal in both eyes. Further evaluation with ganglion cell analysis (GCA = ganglion cell + inner plexiform layer, Cirrus SD-OCT, Carl Zeiss) showed a concentric thinning of this layer in the same area. Although daily and cumulative doses were still under the high toxicity risk parameters, HCQ was suspended. At a follow-up 1 year later, visual acuity was 20/16 without any further changes in OCT or on any other exam. This may be the first case report of insidious bull's eye maculopathy exclusively identified using OCT thickness analysis, in a patient in whom both cumulative and daily dosages were under the high-risk parameters for screening and the averages reported in studies. As ganglion cell analysis has only recently become available, further studies are needed to understand toxicity mechanisms and maybe review screening recommendations.

10 CFR 20.1502 - Conditions requiring individual monitoring of external and internal occupational dose.

Code of Federal Regulations, 2014 CFR

2014-01-01

... internal occupational dose. 20.1502 Section 20.1502 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Surveys and Monitoring § 20.1502 Conditions requiring individual monitoring of external and internal occupational dose. Each licensee shall monitor exposures to radiation and radioactive...

10 CFR 20.1502 - Conditions requiring individual monitoring of external and internal occupational dose.

Code of Federal Regulations, 2012 CFR

2012-01-01

... internal occupational dose. 20.1502 Section 20.1502 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Surveys and Monitoring § 20.1502 Conditions requiring individual monitoring of external and internal occupational dose. Each licensee shall monitor exposures to radiation and radioactive...

10 CFR 20.1502 - Conditions requiring individual monitoring of external and internal occupational dose.

Code of Federal Regulations, 2011 CFR

2011-01-01

... internal occupational dose. 20.1502 Section 20.1502 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Surveys and Monitoring § 20.1502 Conditions requiring individual monitoring of external and internal occupational dose. Each licensee shall monitor exposures to radiation and radioactive...

10 CFR 20.1502 - Conditions requiring individual monitoring of external and internal occupational dose.

Code of Federal Regulations, 2013 CFR

2013-01-01

... internal occupational dose. 20.1502 Section 20.1502 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Surveys and Monitoring § 20.1502 Conditions requiring individual monitoring of external and internal occupational dose. Each licensee shall monitor exposures to radiation and radioactive...

10 CFR 20.1502 - Conditions requiring individual monitoring of external and internal occupational dose.

Code of Federal Regulations, 2010 CFR

2010-01-01

... internal occupational dose. 20.1502 Section 20.1502 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Surveys and Monitoring § 20.1502 Conditions requiring individual monitoring of external and internal occupational dose. Each licensee shall monitor exposures to radiation and radioactive...

Leukemia, lymphoma and multiple myeloma mortality (1950–1999) and incidence (1969–1999) in the Eldorado uranium workers cohort

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

Zablotska, Lydia B., E-mail: Lydia.Zablotska@ucsf.edu; Lane, Rachel S.D.; Frost, Stanley E.

Uranium workers are chronically exposed to low levels of radon decay products (RDP) and gamma (γ) radiation. Risks of leukemia from acute and high doses of γ-radiation are well-characterized, but risks from lower doses and dose-rates and from RDP exposures are controversial. Few studies have evaluated risks of other hematologic cancers in uranium workers. The purpose of this study was to analyze radiation-related risks of hematologic cancers in the cohort of Eldorado uranium miners and processors first employed in 1932–1980 in relation to cumulative RDP exposures and γ-ray doses. The average cumulative RDP exposure was 100.2 working level months andmore » the average cumulative whole-body γ-radiation dose was 52.2 millisievert. We identified 101 deaths and 160 cases of hematologic cancers in the cohort. Overall, male workers had lower mortality and cancer incidence rates for all outcomes compared with the general Canadian male population, a likely healthy worker effect. No statistically significant association between RDP exposure or γ-ray doses, or a combination of both, and mortality or incidence of any hematologic cancer was found. We observed consistent but non-statistically significant increases in risks of chronic lymphocytic leukemia (CLL) and Hodgkin lymphoma (HL) incidence and non-Hodgkin lymphoma (NHL) mortality with increasing γ-ray doses. These findings are consistent with recent studies of increased risks of CLL and NHL incidence after γ-radiation exposure. Further research is necessary to understand risks of other hematologic cancers from low-dose exposures to γ-radiation. - Highlights: • We analyzed long-term follow-up for hematologic cancers of the Eldorado uranium workers. • Workers were exposed to a unique combination of radon decay products (RDP) and gamma (γ) ray doses. • Exposures to RDP and γ-ray doses were not associated with significantly increased risks of cancers. • Radiation risks of chronic lymphocytic leukemia (CLL) and Hodgkin lymphoma were increased. • Study findings provide additional support for radiation-related risks of CLL.« less

Identifying the health risks from very low-dose sparsely ionizing radiation

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

Dreyer, N.A.; Friedlander, E.

1982-06-01

The health risks from low-dose sparsely ionizing (low-LET) radiation have been the subject of continued debate. At present, quantitative estimates of risk are extremely uncertain due to the controversy surrounding both the dosimetry for A-bomb survivor data and the choice of mathematical models for extrapolating risk from high to low doses. Nevertheless, much can be learned about the nature of the health risks by reviewing the epidemiologic literature. We present a summary of diseases which have been associated with low-LET radiation (less than 1000 rad) in at least two independent studies, according to the mean cumulative organ dose at whichmore » the disease was observed. At organ doses of less than or equal to 50 rad, the only diseases that have been reported consistently are thyroid cancer, salivary gland tumors, and leukemia. The first two diseases were observed in association with x-ray epilation of the scalp for tinea capitis, a therapy which is no longer employed. On the other hand, leukemia has been observed repeatedly to occur at cumulative doses of greater than or equal to 30 rad low-LET radiation.« less

Symptoms, airway responsiveness, and exposure to dust in beech and oak wood workers

PubMed Central

Bohadana, A.; Massin, N.; Wild, P.; Toamain, J.; Engel, S.; Goutet, P.

2000-01-01

OBJECTIVES—To investigate the relation between levels of cumulative exposure to wood dust and respiratory symptoms and the occurrence of bronchial hyperresponsiveness among beech and oak workers.
METHODS—114 Male woodworkers from five furniture factories and 13 male unexposed controls were examined. The unexposed control group was supplemented by 200 male historical controls. Statistical analyses were performed excluding and including the historical controls. Dust concentration was measured by personal sampling methods. Cumulative exposure to dust was calculated for each woodworker by multiplying the duration of the work by the intensity of exposure (years.mg/m3). Bronchial hyperresponsiveness was assessed by the methacholine bronchial challenge test. Subjects were labelled methacholine bronchial challenge positive if forced expiratory volume in 1 second (FEV1) fell by ⩾20%. The linear dose-response slope was calculated as the last dose divided by the total dose given.
RESULTS—443 Dust samples were collected. The median cumulative exposure to dust was 110 years.mg/m3 with lower and upper quartiles at 70 and 160 years.mg/m3 Overall, no declines in FEV1 and forced vital capacity (FVC) were found with increasing exposures. A dose-response relation was found between intensity of exposure on the one hand, and sore throat, increased prevalence of positive methacholine bronchial challenge tests, and steeper dose-response slope, on the other.
CONCLUSION—Exposure to oak and beech dust may lead to the development of sore throat and bronchial hyperresponsiveness.


Keywords: bronchial hyperresponsiveness; wood dust; beech; oak PMID:10810114

Effect of high-dose nicotine patch on craving and negative affect leading up to lapse episodes.

PubMed

Ferguson, Stuart G; Shiffman, Saul

2014-07-01

Nicotine patches have been reliably demonstrated to improve smoking cessation outcomes but most users still lapse, and then relapse, during treatment. While patch has been shown to alleviate background cravings, its effects on cue-induced cravings - which have been linked to the occurrence of lapse events - are poorly understood. Here we investigate the effect of nicotine patch on the intensity of craving and negative affect experienced during the hours immediately preceding lapse episodes. Participants were 185 smokers who had quit in the context of a randomized, double-blind trial of high-dose (35 mg) nicotine patch and who lapsed at least once during the first 5 weeks of treatment. Participants used electronic diaries to monitor their smoking, affect, and craving during their cessation attempt. The data suggest that developments on the lapse day - either external events or changes in internal states - caused craving and negative affect to rise, cumulating in the lapse. Nicotine is known to lower background craving and negative affect, but the difference between patch and placebo appeared to dissipate in the hours immediately preceding lapse episodes. Understanding the process by which these symptoms "spike" prior to a lapse - and developing treatments to counter it - are worthy research endeavors.

Development of methods for avian oil toxicity studies using the double crested cormorant (Phalacrocorax auritus).

PubMed

Cunningham, Fred; Dean, Karen; Hanson-Dorr, Katie; Harr, Kendal; Healy, Kate; Horak, Katherine; Link, Jane; Shriner, Susan; Bursian, Steven; Dorr, Brian

2017-07-01

Oral and external dosing methods replicating field exposure were developed using the double crested cormorant (DCCO) to test the toxicity of artificially weathered Deepwater Horizon Mississippi Canyon 252 oil. The majority of previous oil dosing studies conducted on wild-caught birds used gavage methods to dose birds with oil and determine toxicity. However, rapid gut transit time of gavaged oil likely reduces oil absorption. In the present studies, dosing relied on injection of oil into live feeder fish for oral dosing of these piscivorous birds, or applying oil to body contour feathers resulting in transdermal oil exposure and oral exposure through preening. Both oral and external oil dosing studies identified oil-related toxicity endpoints associated with oxidative stress such as hemolytic anemia, liver and kidney damage, and immuno-modulation or compromise. External oil application allowed for controlled study of thermoregulatory stress as well. Infrared thermal images indicated significantly greater surface temperatures and heat loss in treated birds following external oil applications; however, measurements collected by coelomically implanted temperature transmitters showed that internal body temperatures were stable over the course of the study period. Birds exposed to oil externally consumed more fish than control birds, indicating metabolic compensation for thermal stress. Conversely, birds orally dosed with oil experienced hypothermia and consumed less fish compared to control birds. Published by Elsevier Inc.

Analysis of EPR and FISH studies of radiation doses in persons who lived in the upper reaches of the Techa River.

PubMed

Degteva, M O; Shagina, N B; Shishkina, E A; Vozilova, A V; Volchkova, A Y; Vorobiova, M I; Wieser, A; Fattibene, P; Della Monaca, S; Ainsbury, E; Moquet, J; Anspaugh, L R; Napier, B A

2015-11-01

Waterborne radioactive releases into the Techa River from the Mayak Production Association in Russia during 1949-1956 resulted in significant doses to about 30,000 persons who lived in downstream settlements. The residents were exposed to internal and external radiation. Two methods for reconstruction of the external dose are considered in this paper, electron paramagnetic resonance (EPR) measurements of teeth, and fluorescence in situ hybridization (FISH) measurements of chromosome translocations in circulating lymphocytes. The main issue in the application of the EPR and FISH methods for reconstruction of the external dose for the Techa Riverside residents was strontium radioisotopes incorporated in teeth and bones that act as a source of confounding local exposures. In order to estimate and subtract doses from incorporated (89,90)Sr, the EPR and FISH assays were supported by measurements of (90)Sr-body burdens and estimates of (90)Sr concentrations in dental tissues by the luminescence method. The resulting dose estimates derived from EPR to FISH measurements for residents of the upper Techa River were found to be consistent: The mean values vary from 510 to 550 mGy for the villages located close to the site of radioactive release to 130-160 mGy for the more distant villages. The upper bound of individual estimates for both methods is equal to 2.2-2.3 Gy. The EPR- and FISH-based dose estimates were compared with the doses calculated for the donors using the most recent Techa River Dosimetry System (TRDS). The TRDS external dose assessments are based on the data on contamination of the Techa River floodplain, simulation of air kerma above the contaminated soil, age-dependent lifestyles and individual residence histories. For correct comparison, TRDS-based doses were calculated from two sources: external exposure from the contaminated environment and internal exposure from (137)Cs incorporated in donors' soft tissues. It is shown here that the TRDS-based absorbed doses in tooth enamel and muscle are in agreement with EPR- and FISH-based estimates within uncertainty bounds. Basically, this agreement between the estimates has confirmed the validity of external doses calculated with the TRDS.

Childhood Poverty, Cumulative Risk Exposure, and Mental Health in Emerging Adults

PubMed Central

Evans, Gary W.; Cassells, Rochelle C.

2014-01-01

One out of four American children are born into poverty, but little is known about the long-term, mental health implications of early deprivation. The more time in poverty from birth-age-9, the worse mental health as emerging adults (n = 196, M = 17.30 years, 53% male). These results maintain independently of concurrent, adult income levels for self-reported externalizing symptoms and a standard learned helplessness behavioral protocol, but internalizing symptoms were unaffected by childhood poverty. We then demonstrate that part of the reason why early poverty exposure is harmful to mental health among emerging adults is because of elevated cumulative risk exposure assessed at age 13. The significant, prospective, longitudinal relations between early childhood poverty and externalizing symptoms plus learned helplessness behavior are mediated, in part, by exposure to a confluence of psychosocial (violence, family turmoil, child separation from family) and physical (noise, crowding, substandard housing) risk factors during adolescence. PMID:26609499

Development of Safety Assessment Code for Decommissioning of Nuclear Facilities

NASA Astrophysics Data System (ADS)

Shimada, Taro; Ohshima, Soichiro; Sukegawa, Takenori

A safety assessment code, DecDose, for decommissioning of nuclear facilities has been developed, based on the experiences of the decommissioning project of Japan Power Demonstration Reactor (JPDR) at Japan Atomic Energy Research Institute (currently JAEA). DecDose evaluates the annual exposure dose of the public and workers according to the progress of decommissioning, and also evaluates the public dose at accidental situations including fire and explosion. As for the public, both the internal and the external doses are calculated by considering inhalation, ingestion, direct radiation from radioactive aerosols and radioactive depositions, and skyshine radiation from waste containers. For external dose for workers, the dose rate from contaminated components and structures to be dismantled is calculated. Internal dose for workers is calculated by considering dismantling conditions, e.g. cutting speed, cutting length of the components and exhaust velocity. Estimation models for dose rate and staying time were verified by comparison with the actual external dose of workers which were acquired during JPDR decommissioning project. DecDose code is expected to contribute the safety assessment for decommissioning of nuclear facilities.

When there Seem to be No Predetermining Factors: Early Child and Proximal Family Risk Predicting Externalizing Behavior in Young Children Incurring No Distal Family Risk

ERIC Educational Resources Information Center

Roskam, I.; Meunier, J.-C.; Stievenart, M.; Noel, M.-P.

2013-01-01

The main objective of the current study was to examine the impact of two child risk factors, i.e. personality and inhibition, and two proximal family risk factors, i.e. parenting and attachment, and the impact of their cumulative effect on later externalizing behavior among young children incurring no distal family risk. Data were collected in a…

Direct dose mapping versus energy/mass transfer mapping for 4D dose accumulation: fundamental differences and dosimetric consequences.

PubMed

Li, Haisen S; Zhong, Hualiang; Kim, Jinkoo; Glide-Hurst, Carri; Gulam, Misbah; Nurushev, Teamour S; Chetty, Indrin J

2014-01-06

The direct dose mapping (DDM) and energy/mass transfer (EMT) mapping are two essential algorithms for accumulating the dose from different anatomic phases to the reference phase when there is organ motion or tumor/tissue deformation during the delivery of radiation therapy. DDM is based on interpolation of the dose values from one dose grid to another and thus lacks rigor in defining the dose when there are multiple dose values mapped to one dose voxel in the reference phase due to tissue/tumor deformation. On the other hand, EMT counts the total energy and mass transferred to each voxel in the reference phase and calculates the dose by dividing the energy by mass. Therefore it is based on fundamentally sound physics principles. In this study, we implemented the two algorithms and integrated them within the Eclipse treatment planning system. We then compared the clinical dosimetric difference between the two algorithms for ten lung cancer patients receiving stereotactic radiosurgery treatment, by accumulating the delivered dose to the end-of-exhale (EE) phase. Specifically, the respiratory period was divided into ten phases and the dose to each phase was calculated and mapped to the EE phase and then accumulated. The displacement vector field generated by Demons-based registration of the source and reference images was used to transfer the dose and energy. The DDM and EMT algorithms produced noticeably different cumulative dose in the regions with sharp mass density variations and/or high dose gradients. For the planning target volume (PTV) and internal target volume (ITV) minimum dose, the difference was up to 11% and 4% respectively. This suggests that DDM might not be adequate for obtaining an accurate dose distribution of the cumulative plan, instead, EMT should be considered.

Direct dose mapping versus energy/mass transfer mapping for 4D dose accumulation: fundamental differences and dosimetric consequences

NASA Astrophysics Data System (ADS)

Li, Haisen S.; Zhong, Hualiang; Kim, Jinkoo; Glide-Hurst, Carri; Gulam, Misbah; Nurushev, Teamour S.; Chetty, Indrin J.

2014-01-01

The direct dose mapping (DDM) and energy/mass transfer (EMT) mapping are two essential algorithms for accumulating the dose from different anatomic phases to the reference phase when there is organ motion or tumor/tissue deformation during the delivery of radiation therapy. DDM is based on interpolation of the dose values from one dose grid to another and thus lacks rigor in defining the dose when there are multiple dose values mapped to one dose voxel in the reference phase due to tissue/tumor deformation. On the other hand, EMT counts the total energy and mass transferred to each voxel in the reference phase and calculates the dose by dividing the energy by mass. Therefore it is based on fundamentally sound physics principles. In this study, we implemented the two algorithms and integrated them within the Eclipse treatment planning system. We then compared the clinical dosimetric difference between the two algorithms for ten lung cancer patients receiving stereotactic radiosurgery treatment, by accumulating the delivered dose to the end-of-exhale (EE) phase. Specifically, the respiratory period was divided into ten phases and the dose to each phase was calculated and mapped to the EE phase and then accumulated. The displacement vector field generated by Demons-based registration of the source and reference images was used to transfer the dose and energy. The DDM and EMT algorithms produced noticeably different cumulative dose in the regions with sharp mass density variations and/or high dose gradients. For the planning target volume (PTV) and internal target volume (ITV) minimum dose, the difference was up to 11% and 4% respectively. This suggests that DDM might not be adequate for obtaining an accurate dose distribution of the cumulative plan, instead, EMT should be considered.

10 CFR 20.1202 - Compliance with requirements for summation of external and internal doses.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Compliance with requirements for summation of external and internal doses. 20.1202 Section 20.1202 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1202 Compliance with requirements for summation of...

10 CFR 20.1202 - Compliance with requirements for summation of external and internal doses.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Compliance with requirements for summation of external and internal doses. 20.1202 Section 20.1202 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1202 Compliance with requirements for summation of...

10 CFR 20.1202 - Compliance with requirements for summation of external and internal doses.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Compliance with requirements for summation of external and internal doses. 20.1202 Section 20.1202 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1202 Compliance with requirements for summation of...

10 CFR 20.1202 - Compliance with requirements for summation of external and internal doses.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Compliance with requirements for summation of external and internal doses. 20.1202 Section 20.1202 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1202 Compliance with requirements for summation of...

10 CFR 20.1202 - Compliance with requirements for summation of external and internal doses.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Compliance with requirements for summation of external and internal doses. 20.1202 Section 20.1202 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1202 Compliance with requirements for summation of...

Ultrasound-Detected Thyroid Nodule Prevalence and Radiation Dose from Fallout

PubMed Central

Land, C. E.; Zhumadilov, Z.; Gusev, B. I.; Hartshorne, M. H.; Wiest, P. W.; Woodward, P. W.; Crooks, L. A.; Luckyanov, N. K.; Fillmore, C. M.; Carr, Z.; Abisheva, G.; Beck, H. L.; Bouville, A.; Langer, J.; Weinstock, R.; Gordeev, K. I.; Shinkarev, S.; Simon, S. L.

2014-01-01

Settlements near the Semipalatinsk Test Site (SNTS) in northeastern Kazakhstan were exposed to radioactive fallout during 1949–1962. Thyroid disease prevalence among 2994 residents of eight villages was ascertained by ultrasound screening. Malignancy was determined by cytopathology. Individual thyroid doses from external and internal radiation sources were reconstructed from fallout deposition patterns, residential histories and diet, including childhood milk consumption. Point estimates of individual external and internal dose averaged 0.04 Gy (range 0–0.65) and 0.31 Gy (0–9.6), respectively, with a Pearson correlation coefficient of 0.46. Ultrasound-detected thyroid nodule prevalence was 18% and 39% among males and females, respectively. It was significantly and independently associated with both external and internal dose, the main study finding. The estimated relative biological effectiveness of internal compared to external radiation dose was 0.33, with 95% confidence bounds of 0.09–3.11. Prevalence of papillary cancer was 0.9% and was not significantly associated with radiation dose. In terms of excess relative risk per unit dose, our dose–response findings for nodule prevalence are comparable to those from populations exposed to medical X rays and to acute radiation from the Hiroshima and Nagasaki atomic bombings. PMID:18363427

The Effect of Intra-articular Corticosteroids on Articular Cartilage

PubMed Central

Wernecke, Chloe; Braun, Hillary J.; Dragoo, Jason L.

2015-01-01

Background: Intra-articular (IA) corticosteroid therapy has been used for the treatment of inflammation and pain in the knee since the 1950s. Purpose: To review the current literature on the effects of IA corticosteroids on articular cartilage. Study Design: Systematic review. Methods: A MEDLINE and SCOPUS database search was performed, and studies were selected for basic science and clinical trial research on corticosteroids with direct outcome measures of cartilage health. Preliminary searches yielded 1929 articles, and final analysis includes 40 studies. Results: Methylprednisolone, dexamethasone, hydrocortisone, betamethasone, prednisolone, and triamcinolone were reported to display dose-dependent deleterious effects on cartilage morphology, histology, and viability in both in vitro and in vivo models. The beneficial animal in vivo effects of methylprednisolone, hydrocortisone, and triamcinolone occurred at low doses (usually <2-3 mg/dose or 8-12 mg/cumulative total dose in vivo), at which increased cell growth and recovery from damage was observed; the single human clinical trial indicated a beneficial effect of triamcinolone. However, at higher doses (>3 mg/dose or 18-24 mg/cumulative total dose in vivo), corticosteroids were associated with significant gross cartilage damage and chondrocyte toxicity. Dose and time dependency of corticosteroid chondrotoxicity was supported in the in vitro results, however, without clear dose thresholds. Conclusion: Corticosteroids have a time- and dose-dependent effect on articular cartilage, with beneficial effects occurring at low doses and durations and detrimental effects at high doses and durations. Clinically, beneficial effects are supported for IA administration, but the lowest efficacious dose should be used. PMID:26674652

Tumorigenic target cell regions in bone marrow studied by localized dosimetry of 239Pu, 241Am and 233U in the mouse femur.

PubMed

Lord, B I; Austin, A L; Ellender, M; Haines, J W; Harrison, J D

2001-06-01

To study the temporal change in microdistribution of plutonium-239, americium-241 and uranium-233 in the mouse distal femur and to compare and combine calculated radiation doses with those obtained previously for the femoral shaft. Also, to relate doses to relative risks of osteosarcoma and acute myeloid leukaemia. Computer-based image analysis of neutron-induced and alpha-track autoradiographs of sections of mouse femora was used to quantify the microdistribution of (239)Pu, (241)Am and (233)U from 1 to 448 days after intraperitoneal injection. Localized dose-rates and cumulative doses over this period were calculated for different regions of the marrow spaces in trabecular bone. The results were then combined with previous data for doses to the cortical marrow of the femoral shaft. A morphometric analysis of the distal femur was carried out. Initial deposition on endosteal surfaces and dose-rates near to the trabecular surfaces at 1 day were two to four times greater than corresponding results for cortical bone. Burial was most rapid for (233)U, about twice the rate in cortical bone. As in cortical bone, subsequent uptake into the marrow was seen for (239)Pu and (241)Am but not (233)U. Cumulative doses to 448 days for different regions of trabecular marrow were greater than corresponding values for cortical marrow for each radionuclide. Combined doses reflected the greater overall volume of cortical marrow. Cumulative radiation doses to the 10 microm thick band of marrow adjacent to all endosteal surfaces were in the ratio of approximately 7:3:1 for (239)Pu:(241)Am:(233)U. This ratio is not inconsistent with observed incidences of osteosarcoma induction by the three nuclides. Analysis of doses to different depths of marrow, however, showed that although ratios were probably not significantly different to that for a 10 microm depth, better correlations with osteosarcomagenic risk were obtained with 20-40 microm depths. For acute myeloid leukaemia, the closest relationship between relative risk and doses was obtained by considering only the central 5-10% of marrow, which gave a dose ratio of approximately 12:11:1 for (239)Pu:(241)Am:(233)U respectively.

Metronidazole-induced encephalopathy in a patient with liver cirrhosis.

PubMed

Cheong, Hyeong Cheol; Jeong, Taek Geun; Cho, Young Bum; Yang, Bong Joon; Kim, Tae Hyeon; Kim, Haak Cheoul; Cho, Eun-Young

2011-06-01

Encephalopathy is a disorder characterized by altered brain function, which can be attributed to various causes. Encephalopathy associated with metronidazole administration occurs rarely and depends on the cumulative metronidazole dose, and most patients with this condition recover rapidly after discontinuation of therapy. Because metronidazole is metabolized in the liver and can be transported by the cerebrospinal fluid and cross the blood-brain barrier, it may induce encephalopathy even at a low cumulative dose in patients with hepatic dysfunction. We experienced a patient who showed ataxic gait and dysarthric speech after receiving metronidazole for the treatment of hepatic encephalopathy that was not controlled by the administration of lactulose. The patient was diagnosed as metronidazole-induced encephalopathy, and stopping drug administration resulted in a complete recovery from encephalopathy. This case shows that caution should be exercised when administering metronidazole because even a low dose can induce encephalopathy in patients with liver cirrhosis.

Adult Lead Exposure: Time for Change

PubMed Central

Schwartz, Brian S.; Hu, Howard

2007-01-01

We have assembled this mini-monograph on adult lead exposure to provide guidance to clinicians and public health professionals, to summarize recent thinking on lead biomarkers and their relevance to epidemiologic research, and to review two key lead-related outcomes, namely, cardiovascular and cognitive. The lead standards of the U.S. Occupational Safety and Health Administration are woefully out of date given the growing evidence of the health effects of lead at levels of exposure previously thought to be safe, particularly newly recognized persistent or progressive effects of cumulative dose. The growing body of scientific evidence suggests that occupational standards should limit recent dose to prevent the acute effects of lead and separately limit cumulative dose to prevent the chronic effects of lead. We hope this mini-monograph will motivate renewed discussion of ways to protect lead-exposed adults in the United States and around the world. PMID:17431498

Cumulative dose 60Co gamma irradiation effects on AlGaN/GaN Schottky diodes and its area dependence

NASA Astrophysics Data System (ADS)

Sharma, Chandan; Laishram, Robert; Rawal, Dipendra Singh; Vinayak, Seema; Singh, Rajendra

2018-04-01

Cumulative dose gamma radiation effects on current-voltage characteristics of GaN Schottky diodes have been investigated. The different area diodes have been fabricated on AlGaN/GaN high electron mobility transistor (HEMT) epi-layer structure grown over SiC substrate and irradiated with a dose up to the order of 104 Gray (Gy). Post irradiation characterization shows a shift in the turn-on voltage and improvement in reverse leakage current. Other calculated parameters include Schottky barrier height, ideality factor and reverse saturation current. Schottky barrier height has been decreased whereas reverse saturation current shows an increase in the value post irradiation with improvement in the ideality factor. Transfer length measurement (TLM) characterization shows an improvement in the contact resistance. Finally, diodes with larger area have more variation in the calculated parameters due to the induced local heating effect.

Fault Tolerant Characteristics of Artificial Neural Network Electronic Hardware

NASA Technical Reports Server (NTRS)

Zee, Frank

1995-01-01

The fault tolerant characteristics of analog-VLSI artificial neural network (with 32 neurons and 532 synapses) chips are studied by exposing them to high energy electrons, high energy protons, and gamma ionizing radiations under biased and unbiased conditions. The biased chips became nonfunctional after receiving a cumulative dose of less than 20 krads, while the unbiased chips only started to show degradation with a cumulative dose of over 100 krads. As the total radiation dose increased, all the components demonstrated graceful degradation. The analog sigmoidal function of the neuron became steeper (increase in gain), current leakage from the synapses progressively shifted the sigmoidal curve, and the digital memory of the synapses and the memory addressing circuits began to gradually fail. From these radiation experiments, we can learn how to modify certain designs of the neural network electronic hardware without using radiation-hardening techniques to increase its reliability and fault tolerance.

Assessment of radiation doses from residential smoke detectors that contain americium-241

NASA Astrophysics Data System (ADS)

Odonnell, F. R.; Etnier, E. L.; Holton, G. A.; Travis, C. C.

1981-10-01

External dose equivalents and internal dose commitments were estimated for individuals and populations from annual distribution, use, and disposal of 10 million ionization chamber smoke detectors that contain 110 kBq americium-241 each. Under exposure scenarios developed for normal distribution, use, and disposal using the best available information, annual external dose equivalents to average individuals were estimated to range from 4 fSv to 20 nSv for total body and from 7 fSv to 40 nSv for bone. Internal dose commitments to individuals under post disposal scenarios were estimated to range from 0.006 to 80 micro-Sv (0.0006 to 8 mrem) to total body and from 0.06 to 800 micro-Sv to bone. The total collective dose (the sum of external dose equivalents and 50-year internal dose commitments) for all individuals involved with distribution, use, or disposal of 10 million smoke detectors was estimated to be about 0.38 person-Sv (38 person-rem) to total body and 00 ft squared.

Pneumocystis jirovecii pneumonia induced by low-dose methotrexate in a patient with chronic urticaria.

PubMed

Wang, Sheng-Huei; Tang, Shih-En; Li, Yu-Huei; Wei, Kuang-Yu; Chang, Chan-Yuan

2017-01-01

Methotrexate has immunosuppressive effects and is administered for refractory chronic urticaria. We present a case of Pneumocystis jirovecii pneumonia in a patient with refractory chronic urticaria managed by low-dose weekly methotrexate treatment (total cumulative dose 195mg). Our study highlights the importance of providing prompt diagnosis and treatment of Pneumocystis jirovecii pneumonia in patients with chronic urticaria under methotrexate therapy.

FRAMEWORK FOR CUMULATIVE RISK ASSESSMENT (EXTERNAL REVIEW DRAFT)

EPA Science Inventory

Several reports have highlighted the importance of understanding the accumulation of risks from multiple environmental stressors. These include the National Research Councils 1994 report Science and Judgment in Risk Assessment and the 1997 report by the Presidential/Congressional...

Effect of antiretroviral therapy use and adherence on the risk of hyperlipidemia among HIV-infected patients, in the highly active antiretroviral therapy era

PubMed Central

Tsai, Fuu-Jen; Cheng, Chi-Fung; Lai, Chih-Ho; Wu, Yang-Chang; Ho, Mao-Wang; Wang, Jen-Hsien; Tien, Ni; Liu, Xiang; Tsang, Hsinyi; Lin, Ting-Hsu; Liao, Chiu-Chu; Huang, Shao-Mei; Li, Ju-Pi; Lin, Jung-Chun; Lin, Chih-Chien; Chen, Jin-Hua; Liang, Wen-Miin; Lin, Ying-Ju

2017-01-01

HIV-infected patients exposed to antiretroviral therapy (ART) have an increased risk for hyperlipidemia and cardiovascular disease. We performed a longitudinal, comprehensive, and population-based study to investigate the cumulative effect of different types of ART regimens on hyperlipidemia risk in the Taiwanese HIV/ART cohort. A total of 13,370 HIV-infected patients (2,674 hyperlipidemia and 10,696 non-hyperlipidemia patients) were recruited after matching for age, gender, and the first diagnosis date of HIV infection by using the National Health Insurance Research Database in Taiwan. Hyperlipidemia risk associated with cumulative ART use, ART adherence, and their combination was assessed. The matched hyperlipidemia group had a larger number of patients using ART and a higher incidence of comorbidities, specifically, respiratory disease and diabetes. Patients with high ART dosage and dose-dependent manner adherence, respectively, demonstrated an increased risk of hyperlipidemia. For single ART regimens, patients receiving nucleoside reverse-transcriptase inhibitors (NRTI/NRTI)- containing regimen had the highest hyperlipidemia risk, followed by protease inhibitor (PI)- containing and non-NRTI- containing regimens. For combination ART regimens, patients receiving a NRTI/NRTI + PI regimen had the highest hyperlipidemia risk. An increased cumulative drug dose was observed in patients who received the PI, NRTI/NRTI, NRTI, and NNRTI regimens in the hyperlipidemia group, when compared to the non-hyperlipidemia group. In conclusion, ART cumulative use, adherence, and regimen may affect hyperlipidemia risk among HIV-infected patients in a dose-dependent manner. PMID:29290955

Cardiac glycosides use and the risk of lung cancer: a nested case-control study.

PubMed

Couraud, Sébastien; Azoulay, Laurent; Dell'Aniello, Sophie; Suissa, Samy

2014-08-08

Two studies have reported statistically significant associations between the use of cardiac glycosides (CGs) and an increased risk of lung cancer. However, these studies had a number of methodological limitations. Thus, the objective of this study was to assess this association in a large population-based cohort of patients. We used the United Kingdom Clinical Practice Research Datalink (CPRD) to identify a cohort of patients, at least 40 years of age, newly-diagnosed with heart failure, or supra-ventricular arrhythmia. A nested case-control analysis was conducted where each incident case of lung cancer identified during follow-up was randomly matched with up to 10 controls. Exposure to CGs was assessed in terms of ever use, cumulative duration of use and cumulative dose. Rate ratios (RRs) with 95% confidence intervals (CIs) were estimated using conditional logistic regression after adjusting for potential confounders. A total of 129,002 patients were included, and followed for a mean (SD) of 4.7 (3.8) years. During follow-up, 1237 patients were newly-diagnosed with lung cancer. Overall, ever use of CGs was not associated with an increased risk of lung cancer when compared to never use (RR = 1.09, 95% CI: 0.94-1.26). In addition, no dose-response relationship was observed in terms of cumulative duration of use and cumulative dose with all RRs around the null value across quartile categories. The results of this large population-based study indicate that the use of CGs is not associated with an increased risk of lung cancer.

A novel tool for user-friendly estimation of natural, diagnostic and professional radiation risk: Radio-Risk software.

PubMed

Carpeggiani, Clara; Paterni, Marco; Caramella, Davide; Vano, Eliseo; Semelka, Richard C; Picano, Eugenio

2012-11-01

Awareness of radiological risk is low among doctors and patients. An educational/decision tool that considers each patient' s cumulative lifetime radiation exposure would facilitate provider-patient communication. The purpose of this work was to develop user-friendly software for simple estimation and communication of radiological risk to patients and doctors as a part of the SUIT-Heart (Stop Useless Imaging Testing in Heart disease) Project of the Tuscany Region. We developed a novel software program (PC-platform, Windows OS fully downloadable at http://suit-heart.ifc.cnr.it) considering reference dose estimates from American Heart Association Radiological Imaging 2009 guidelines and UK Royal College of Radiology 2007 guidelines. Cancer age and gender-weighted risk were derived from Biological Effects of Ionising Radiation VII Committee, 2006. With simple input functions (demographics, age, gender) the user selects from a predetermined menu variables relating to natural (e.g., airplane flights and geo-tracked background exposure), professional (e.g., cath lab workers) and medical (e.g., CT, cardiac scintigraphy, coronary stenting) sources. The program provides a simple numeric (cumulative effective dose in milliSievert, mSv, and equivalent number of chest X-rays) and graphic (cumulative temporal trends of exposure, cancer cases out of 100 exposed persons) display. A simple software program allows straightforward estimation of cumulative dose (in multiples of chest X-rays) and risk (in extra % lifetime cancer risk), with simple numbers quantifying lifetime extra cancer risk. Pictorial display of radiation risk may be valuable for increasing radiological awareness in cardiologists. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

RISK ASSESSMENT FOR CRYPTOSPORIDIUM: A HIERARCHICAL BAYESIAN ANALYSIS OF HUMAN DOSE-RESPONSE DATA. (R829180)

EPA Science Inventory

Three dose–response studies were conducted with healthy volunteers using different Cryptosporidium parvum isolates (IOWA, TAMU, and UCP). The study data were previously analyzed for median infectious dose (ID₅₀) using a simple cumulative percent endpoi...

Association of Antidepressant Medications With Incident Type 2 Diabetes Among Medicaid-Insured Youths.

PubMed

Burcu, Mehmet; Zito, Julie M; Safer, Daniel J; Magder, Laurence S; dosReis, Susan; Shaya, Fadia T; Rosenthal, Geoffrey L

2017-12-01

Antidepressants are one of the most commonly prescribed classes of psychotropic medications among US youths. For adults, there is emerging evidence on the increased risk of type 2 diabetes in association with antidepressant use. However, little is known about the antidepressant treatment-emergent risk of type 2 diabetes among youths. To assess the association between antidepressant use and the risk of incident type 2 diabetes in youths by antidepressant subclass and according to duration of use, cumulative dose, and average daily dose. A retrospective cohort study was conducted using Medicaid claims data from 4 geographically diverse, large states of youths 5 to 20 years of age who initiated antidepressant treatment from January 1, 2005, to December 31, 2009. Antidepressant use (selective serotonin reuptake inhibitors [SSRIs] or serotonin-norepinephrine reuptake inhibitors [SNRIs], tricyclic or other cyclic antidepressants, and other antidepressants) was assessed using the following 4 time-varying measures: current or former use, duration of use, cumulative dose, and average daily dose. Incident type 2 diabetes was assessed using discrete-time failure models, adjusting for disease risk score estimated using more than 125 baseline and time-dependent covariates. In this cohort of 119 608 youths aged 5 to 20 years who initiated antidepressant treatment (59 087 female youths and 60 521 male youths; 54.7% between 5 and 14 years of age) with a mean follow-up of 22.8 months, 79 285 [66.3%] had SSRI or SNRI exposure. The risk of type 2 diabetes was significantly greater during current use than former use of SSRIs or SNRIs (absolute risk, 1.29 per 10 000 person-months vs 0.64 per 10 000 person-months; adjusted relative risk [RR], 1.88; 95% CI, 1.34-2.64) and tricyclic or other cyclic antidepressants (absolute risk, 0.89 per 10 000 person-months vs 0.48 per 10 000 person-months; RR, 2.15; 95% CI, 1.06-4.36), but not of other antidepressants (absolute risk, 1.15 per 10 000 person-months vs 1.12 per 10 000 person-months; RR, 0.99; 95% CI, 0.66-1.50). Furthermore, for youths currently using SSRIs or SNRIs, the risk of type 2 diabetes increased with the duration of use (RR, 2.66; 95% CI, 1.45-4.88 for >210 days and RR, 2.56; 95% CI, 1.29-5.08 for 151-210 days compared with 1-90 days) and with the cumulative dose (RR, 2.44; 95% CI, 1.35-4.43 for >4500 mg and RR, 2.17; 95% CI, 1.07-4.40 for 3001-4500 mg compared with 1-1500 mg in fluoxetine hydrochloride dose equivalents). By contrast, neither the duration nor the cumulative dose of other antidepressants was associated with an increased risk of type 2 diabetes. The risk of type 2 diabetes increased significantly with the average daily dose among youths with more than 150 days of SSRI or SNRI use (RR, 2.39; 95% CI, 1.04-5.52 for >15.0 vs ≤15.0 mg/d) but not among youths with 1 to 150 days of SSRI or SNRI use. In a large cohort of youths insured by Medicaid, the use of SSRIs or SNRIs-the most commonly used antidepressant subclass-was associated with an increased risk of type 2 diabetes that intensified with increasing duration of use, cumulative dose, and average daily dose.

Repeat Gamma-Knife Radiosurgery for Refractory or Recurrent Trigeminal Neuralgia with Consideration About the Optimal Second Dose.

PubMed

Park, Seong-Cheol; Kwon, Do Hoon; Lee, Do Hee; Lee, Jung Kyo

2016-02-01

To investigate adequate radiation doses for repeat Gamma Knife radiosurgery (GKS) for trigeminal neuralgia in our series and meta-analysis. Fourteen patients treated by ipsilateral repeat GKS for trigeminal neuralgia were included. Median age of patients was 65 years (range, 28-78), the median target dose, 140-180). Patients were followed a median of 10.8 months (range, 1-151) after the second gamma-knife surgery. Brainstem dose analysis and vote-counting meta-analysis of 19 studies were performed. After the second gamma-knife radiosurgeries, pain was relieved effectively in 12 patients (86%; Barrow Neurological Institute Pain Intensity Score I-III). Post-gamma-knife radiosurgery trigeminal nerve deficits were mild in 5 patients. No serious anesthesia dolorosa was occurred. The second GKS radiation dose ≤ 60 Gy was significantly associated with worse pain control outcome (P = 0.018 in our series, permutation analysis of variance, and P = 0.009 in the meta-analysis, 2-tailed Fisher's exact test). Cumulative dose ≤ 140-150 Gy was significantly associated with poor pain control outcome (P = 0.033 in our series and P = 0.013 in the meta-analysis, 2-tailed Fisher's exact test). A cumulative brainstem edge dose >12 Gy tended to be associated with trigeminal nerve deficit (P = 0.077). Our study suggests that the second GKS dose is a potentially important factor. Copyright © 2016 Elsevier Inc. All rights reserved.

Detection of non-Gaussian fluctuations in a quantum point contact.

PubMed

Gershon, G; Bomze, Yu; Sukhorukov, E V; Reznikov, M

2008-07-04

An experimental study of current fluctuations through a tunable transmission barrier, a quantum point contact, is reported. We measure the probability distribution function of transmitted charge with precision sufficient to extract the first three cumulants. To obtain the intrinsic quantities, corresponding to voltage-biased barrier, we employ a procedure that accounts for the response of the external circuit and the amplifier. The third cumulant, obtained with a high precision, is found to agree with the prediction for the statistics of transport in the non-Poissonian regime.

Detection of Non-Gaussian Fluctuations in a Quantum Point Contact

NASA Astrophysics Data System (ADS)

Gershon, G.; Bomze, Yu.; Sukhorukov, E. V.; Reznikov, M.

2008-07-01

An experimental study of current fluctuations through a tunable transmission barrier, a quantum point contact, is reported. We measure the probability distribution function of transmitted charge with precision sufficient to extract the first three cumulants. To obtain the intrinsic quantities, corresponding to voltage-biased barrier, we employ a procedure that accounts for the response of the external circuit and the amplifier. The third cumulant, obtained with a high precision, is found to agree with the prediction for the statistics of transport in the non-Poissonian regime.

Macular retinal ganglion cell-inner plexiform layer thickness in patients on hydroxychloroquine therapy.

PubMed

Lee, Min Gyu; Kim, Sang Jin; Ham, Don-Il; Kang, Se Woong; Kee, Changwon; Lee, Jaejoon; Cha, Hoon-Suk; Koh, Eun-Mi

2014-11-25

We evaluated macular ganglion cell-inner plexiform layer (GC-IPL) thickness using spectral-domain optical coherence tomography (SD-OCT) in patients with chronic exposure to hydroxychloroquine (HCQ). This study included 130 subjects, who were divided into three groups: Group 1A, 55 patients with HCQ use ≥5 years; Group 1B, 46 patients with HCQ use <5 years; and Group 2, 29 normal controls. In all patients with exposure to HCQ, fundus examination, automated threshold perimetry, fundus autofluorescence photography, SD-OCT, and GC-IPL thickness measurement using the Cirrus HD-OCT ganglion cell analysis algorithm were performed. Average and minimum macular GC-IPL thickness were compared between subjects groups, and correlations between GC-IPL thickness and duration or total dose of HCQ use were analyzed. Among the 101 patients of Group 1, six patients who showed clinically evident HCQ retinopathy also showed markedly thin macular GC-IPL. In addition, weak but significant negative correlations were observed between the average and minimum GC-IPL thickness of Group 1 patients and cumulative dose of HCQ, even when analyzing without the six patients with HCQ retinopathy. However, when analyzing after exclusion of patients with high cumulative doses (>1000 g), significant correlations were not observed. This study revealed that macular GC-IPL thickness did not show definite correlations with HCQ use. However, some patients, especially with HCQ retinopathy or high cumulative doses, showed thin GC-IPL. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

WE-E-18A-04: Precision In-Vivo Dosimetry Using Optically Stimulated Luminescence Dosimeters and a Pulsed-Stimulating Dose Reader

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

Chen, Q; Herrick, A; Hoke, S

Purpose: A new readout technology based on pulsed optically stimulating luminescence is introduced (microSTARii, Landauer, Inc, Glenwood, IL60425). This investigation searches for approaches that maximizes the dosimetry accuracy in clinical applications. Methods: The sensitivity of each optically stimulated luminescence dosimeter (OSLD) was initially characterized by exposing it to a given radiation beam. After readout, the luminescence signal stored in the OSLD was erased by exposing its sensing area to a 21W white LED light for 24 hours. A set of OSLDs with consistent sensitivities was selected to calibrate the dose reader. Higher order nonlinear curves were also derived from themore » calibration readings. OSLDs with cumulative doses below 15 Gy were reused. Before an in-vivo dosimetry, the OSLD luminescence signal was erased with the white LED light. Results: For a set of 68 manufacturer-screened OSLDs, the measured sensitivities vary in a range of 17.3%. A sub-set of the OSLDs with sensitivities within ±1% was selected for the reader calibration. Three OSLDs in a group were exposed to a given radiation. Nine groups were exposed to radiation doses ranging from 0 to 13 Gy. Additional verifications demonstrated that the reader uncertainty is about 3%. With an external calibration function derived by fitting the OSLD readings to a 3rd-order polynomial, the dosimetry uncertainty dropped to 0.5%. The dose-luminescence response curves of individual OSLDs were characterized. All curves converge within 1% after the sensitivity correction. With all uncertainties considered, the systematic uncertainty is about 2%. Additional tests emulating in-vivo dosimetry by exposing the OSLDs under different radiation sources confirmed the claim. Conclusion: The sensitivity of individual OSLD should be characterized initially. A 3rd-order polynomial function is a more accurate representation of the dose-luminescence response curve. The dosimetry uncertainty specified by the manufacturer is 4%. Following the proposed approach, it can be controlled to 2%.« less

Antipsychotic dose equivalents and dose-years: a standardized method for comparing exposure to different drugs.

PubMed

Andreasen, Nancy C; Pressler, Marcus; Nopoulos, Peg; Miller, Del; Ho, Beng-Choon

2010-02-01

A standardized quantitative method for comparing dosages of different drugs is a useful tool for designing clinical trials and for examining the effects of long-term medication side effects such as tardive dyskinesia. Such a method requires establishing dose equivalents. An expert consensus group has published charts of equivalent doses for various antipsychotic medications for first- and second-generation medications. These charts were used in this study. Regression was used to compare each drug in the experts' charts to chlorpromazine and haloperidol and to create formulas for each relationship. The formulas were solved for chlorpromazine 100 mg and haloperidol 2 mg to derive new chlorpromazine and haloperidol equivalents. The formulas were incorporated into our definition of dose-years such that 100 mg/day of chlorpromazine equivalent or 2 mg/day of haloperidol equivalent taken for 1 year is equal to one dose-year. All comparisons to chlorpromazine and haloperidol were highly linear with R(2) values greater than .9. A power transformation further improved linearity. By deriving a unique formula that converts doses to chlorpromazine or haloperidol equivalents, we can compare otherwise dissimilar drugs. These equivalents can be multiplied by the time an individual has been on a given dose to derive a cumulative value measured in dose-years in the form of (chlorpromazine equivalent in mg) x (time on dose measured in years). After each dose has been converted to dose-years, the results can be summed to provide a cumulative quantitative measure of lifetime exposure. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Use of fentanyl and midazolam in mechanically ventilated children--Does the method of infusion matter?

PubMed

da Silva, Paulo Sérgio Lucas; Reis, Maria Eunice; de Aguiar, Vânia Euzébio; Fonseca, Marcelo Cunio Machado

2016-04-01

Benzodiazepines and opioids are commonly used in pediatric intensive care unit. However, there is no previous study assessing the use of administering these drugs combined (single solution) or separately. We sought to evaluate the impact of these 2 different methods of providing sedation/analgesia in pediatric intensive care unit. One hundred twelve patients mechanically ventilated for more than 48 hours were randomized to receive a protocolized sedation regime comprising midazolam and fentanyl either separately (group 1, 57 patients) or combined as a single solution (group 2, 55 patients). Primary end point variable was the cumulated dose of midazolam and fentanyl. The median cumulated doses of both fentanyl (0.19 vs 0.37 mg/kg, P < .05) and midazolam (28.8 vs 45.6 mg/kg, P < .05) required in group 2 were higher when compared with those of group 1. Moreover, group 2 patients had a significantly longer time of vasopressor drugs requirement and a higher number of patients developing tolerance. Patients who received a single solution of midazolam and fentanyl had a higher cumulated dose of compared with those patients who did not. The potential risk for long-term neurologic effects on developing brains associated with this finding should be considered. Copyright © 2015 Elsevier Inc. All rights reserved.

The safety of intraocular methotrexate in silicone-filled eyes.

PubMed

Hardwig, Paul W; Pulido, Jose S; Bakri, Sophie J

2008-10-01

Intraocular methotrexate has been safely used in eyes with primary CNS lymphoma (PCNSL), and in eyes with uveitis and proliferative diabetic retinopathy. Dosing in silicone-filled eyes was reduced from a standard 400 microg intravitreal injection due to concerns of toxicity. The present study reports the visual results of non-PCNSL, silicone-filled eyes treated with intravitreal methotrexate using cumulative dosages ranging from 200 microg to 1,200 microg. In this retrospective case series, all patients with silicone-filled eyes who received intraocular methotrexate were included. Patients were observed with serial ophthalmic examinations. Best-corrected visual acuity was measured by Snellen acuity. Pretreatment acuities were compared to those obtained at last follow-up. The cohort included 12 patients (13 eyes) with disease other than PCNSL. The cumulative dose of intraocular methotrexate in any one patient ranged from 200 microg to 1,200 microg. Mean follow-up was 9 months (median, 10 months; range, 2 weeks to 16 months). Best-corrected vision at last follow-up was either stable or improved from pretreatment acuity in 12 of 13 eyes. Preservation of acuity in 12 of 13 study eyes suggests that intravitreal methotrexate in a cumulative dose of up to 1,200 microg is safe in silicone-filled eyes.

Estimation of RF energy absorbed in the brain from mobile phones in the Interphone Study.

PubMed

Cardis, E; Varsier, N; Bowman, J D; Deltour, I; Figuerola, J; Mann, S; Moissonnier, M; Taki, M; Vecchia, P; Villegas, R; Vrijheid, M; Wake, K; Wiart, J

2011-09-01

The objective of this study was to develop an estimate of a radio frequency (RF) dose as the amount of mobile phone RF energy absorbed at the location of a brain tumour, for use in the Interphone Epidemiological Study. We systematically evaluated and quantified all the main parameters thought to influence the amount of specific RF energy absorbed in the brain from mobile telephone use. For this, we identified the likely important determinants of RF specific energy absorption rate during protocol and questionnaire design, we collected information from study subjects, network operators and laboratories involved in specific energy absorption rate measurements and we studied potential modifiers of phone output through the use of software-modified phones. Data collected were analysed to assess the relative importance of the different factors, leading to the development of an algorithm to evaluate the total cumulative specific RF energy (in joules per kilogram), or dose, absorbed at a particular location in the brain. This algorithm was applied to Interphone Study subjects in five countries. The main determinants of total cumulative specific RF energy from mobile phones were communication system and frequency band, location in the brain and amount and duration of mobile phone use. Though there was substantial agreement between categorisation of subjects by cumulative specific RF energy and cumulative call time, misclassification was non-negligible, particularly at higher frequency bands. Factors such as adaptive power control (except in Code Division Multiple Access networks), discontinuous transmission and conditions of phone use were found to have a relatively minor influence on total cumulative specific RF energy. While amount and duration of use are important determinants of RF dose in the brain, their impact can be substantially modified by communication system, frequency band and location in the brain. It is important to take these into account in analyses of risk of brain tumours from RF exposure from mobile phones.

Estimation of RF energy absorbed in the brain from mobile phones in the Interphone Study

PubMed Central

Varsier, N; Bowman, J D; Deltour, I; Figuerola, J; Mann, S; Moissonnier, M; Taki, M; Vecchia, P; Villegas, R; Vrijheid, M; Wake, K; Wiart, J

2011-01-01

Objectives The objective of this study was to develop an estimate of a radio frequency (RF) dose as the amount of mobile phone RF energy absorbed at the location of a brain tumour, for use in the Interphone Epidemiological Study. Methods We systematically evaluated and quantified all the main parameters thought to influence the amount of specific RF energy absorbed in the brain from mobile telephone use. For this, we identified the likely important determinants of RF specific energy absorption rate during protocol and questionnaire design, we collected information from study subjects, network operators and laboratories involved in specific energy absorption rate measurements and we studied potential modifiers of phone output through the use of software-modified phones. Data collected were analysed to assess the relative importance of the different factors, leading to the development of an algorithm to evaluate the total cumulative specific RF energy (in joules per kilogram), or dose, absorbed at a particular location in the brain. This algorithm was applied to Interphone Study subjects in five countries. Results The main determinants of total cumulative specific RF energy from mobile phones were communication system and frequency band, location in the brain and amount and duration of mobile phone use. Though there was substantial agreement between categorisation of subjects by cumulative specific RF energy and cumulative call time, misclassification was non-negligible, particularly at higher frequency bands. Factors such as adaptive power control (except in Code Division Multiple Access networks), discontinuous transmission and conditions of phone use were found to have a relatively minor influence on total cumulative specific RF energy. Conclusions While amount and duration of use are important determinants of RF dose in the brain, their impact can be substantially modified by communication system, frequency band and location in the brain. It is important to take these into account in analyses of risk of brain tumours from RF exposure from mobile phones. PMID:21659468

Effect of Intrathecal Bupivacaine Dose on the Success of External Cephalic Version for Breech Presentation: A Prospective, Randomized, Blinded Clinical Trial.

PubMed

Chalifoux, Laurie A; Bauchat, Jeanette R; Higgins, Nicole; Toledo, Paloma; Peralta, Feyce M; Farrer, Jason; Gerber, Susan E; McCarthy, Robert J; Sullivan, John T

2017-10-01

Breech presentation is a leading cause of cesarean delivery. The use of neuraxial anesthesia increases the success rate of external cephalic version procedures for breech presentation and reduces cesarean delivery rates for fetal malpresentation. Meta-analysis suggests that higher-dose neuraxial techniques increase external cephalic version success to a greater extent than lower-dose techniques, but no randomized study has evaluated the dose-response effect. We hypothesized that increasing the intrathecal bupivacaine dose would be associated with increased external cephalic version success. We conducted a randomized, double-blind trial to assess the effect of four intrathecal bupivacaine doses (2.5, 5.0, 7.5, 10.0 mg) combined with fentanyl 15 μg on the success rate of external cephalic version for breech presentation. Secondary outcomes included mode of delivery, indication for cesarean delivery, and length of stay. A total of 240 subjects were enrolled, and 239 received the intervention. External cephalic version was successful in 123 (51.5%) of 239 patients. Compared with bupivacaine 2.5 mg, the odds (99% CI) for a successful version were 1.0 (0.4 to 2.6), 1.0 (0.4 to 2.7), and 0.9 (0.4 to 2.4) for bupivacaine 5.0, 7.5, and 10.0 mg, respectively (P = 0.99). There were no differences in the cesarean delivery rate (P = 0.76) or indication for cesarean delivery (P = 0.82). Time to discharge was increased 60 min (16 to 116 min) with bupivacaine 7.5 mg or higher as compared with 2.5 mg (P = 0.004). A dose of intrathecal bupivacaine greater than 2.5 mg does not lead to an additional increase in external cephalic procedural success or a reduction in cesarean delivery.

SU-F-T-151: Measurement Evaluation of Skin Dose in Scanning Proton Beam Therapy for Breast Cancer

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

Yu, J; Nichols, E; Strauss, D

Purpose: To measure the skin dose and compare it with the calculated dose from a treatment planning system (TPS) for breast cancer treatment using scanning proton beam therapy (SPBT). Methods: A single en-face-beam SPBT plan was generated by a commercial TPS for two breast cancer patients. The treatment volumes were the entire breasts (218 cc and 1500 cc) prescribed to 50.4 Gy (RBE) in 28 fractions. A range shifter of 5 cm water equivalent thickness was used. The organ at risk (skin) was defined to be 5 mm thick from the surface. The skin doses were measured in water withmore » an ADCL calibrated parallel plate (PP) chamber. The measured data were compared with the values calculated in the TPS. Skin dose calculations can be subject to uncertainties created by the definition of the external contour and the limitations of the correction based algorithms, such as proton convolution superposition. Hence, the external contours were expanded by 0, 3 mm and 1 cm to include additional pixels for dose calculation. In addition, to examine the effects of the cloth gown on the skin dose, the skin dose measurements were conducted with and without gown. Results: On average the measured skin dose was 4% higher than the calculated values. At deeper depths, the measured and calculated doses were in better agreement (< 2%). Large discrepancy occur for the dose calculated without external expansion due to volume averaging. The addition of the gown only increased the measured skin dose by 0.4%. Conclusion: The implemented TPS underestimated the skin dose for breast treatments. Superficial dose calculation without external expansion would result in large errors for SPBT for breast cancer.« less

HADOC: a computer code for calculation of external and inhalation doses from acute radionuclide releases

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

Strenge, D.L.; Peloquin, R.A.

The computer code HADOC (Hanford Acute Dose Calculations) is described and instructions for its use are presented. The code calculates external dose from air submersion and inhalation doses following acute radionuclide releases. Atmospheric dispersion is calculated using the Hanford model with options to determine maximum conditions. Building wake effects and terrain variation may also be considered. Doses are calculated using dose conversion factor supplied in a data library. Doses are reported for one and fifty year dose commitment periods for the maximum individual and the regional population (within 50 miles). The fractional contribution to dose by radionuclide and exposure modemore » are also printed if requested.« less

Radiation dose due to radon and thoron progeny inhalation in high-level natural radiation areas of Kerala, India.

PubMed

Omori, Yasutaka; Tokonami, Shinji; Sahoo, Sarata Kumar; Ishikawa, Tetsuo; Sorimachi, Atsuyuki; Hosoda, Masahiro; Kudo, Hiromi; Pornnumpa, Chanis; Nair, Raghu Ram K; Jayalekshmi, Padmavaty Amma; Sebastian, Paul; Akiba, Suminori

2017-03-20

In order to evaluate internal exposure to radon and thoron, concentrations for radon, thoron, and thoron progeny were measured for 259 dwellings located in high background radiation areas (HBRAs, outdoor external dose: 3-5 mGy y -1 ) and low background radiation areas (control areas, outdoor external dose: 1 mGy y -1 ) in Karunagappally Taluk, Kerala, India. The measurements were conducted using passive-type radon-thoron detectors and thoron progeny detectors over two six-month measurement periods from June 2010 to June 2011. The results showed no major differences in radon and thoron progeny concentrations between the HBRAs and the control areas. The geometric mean of the annual effective dose due to radon and thoron was calculated as 0.10 and 0.44 mSv, respectively. The doses were small, but not negligible compared with the external dose in the two areas.

Nonmetastatic osteosarcoma of the extremity. Neoadjuvant chemotherapy with methotrexate, cisplatin, doxorubicin and ifosfamide. An Italian Sarcoma Group study (ISG/OS-Oss).

PubMed

Ferrari, Stefano; Meazza, Cristina; Palmerini, Emanuela; Tamburini, Angela; Fagioli, Franca; Cozza, Raffaele; Ferraresi, Virginia; Bisogno, Gianni; Mascarin, Maurizio; Cefalo, Graziella; Manfrini, Marco; Capanna, Rodolfo; Biagini, Roberto; Donati, Davide; Picci, Piero

2014-01-01

Based on the results of the ISG/OS-1 study, the MAP regimen (methotrexate [MTX], doxorubicin [ADM] and cisplatin [CDP] with the addition of ifosfamide [IFO] in poor-responder patients) was investigated in patients with nonmetastatic osteosarcoma of the extremity (ISG/OS-Oss study). Compared with the ISG/OS-1 study (cumulative doses: ADM 420 mg/m(2), MTX 120 g/m(2), CDP 600 mg/m(2), IFO 30 g/m(2)), the ISG/OS-Oss study reduced the number of MTX cycles from 10 to 5 (cumulative MTX dose: 60 g/m(2)) in order to diminish treatment duration and toxicity. From January 2007 to June 2011, 171 patients (median age 16 years, 60% males) were registered. The limb salvage rate was 94% and the good pathologic response rate 51% (these figures were 92% and 48%, respectively, in the ISG/OS-1 study). At a median follow-up of 39 months (range, 4-80), the 5-year overall survival rate was 80% (95% CI, 73%-87%) and the event-free survival was 50% (95% CI, 39%-59%). For comparison, the 5-year overall and event-free survival rates in ISG/OS-1 were 73% (95% CI, 65%-81%) and 64% (95% CI, 56%-73%), respectively. This study confirms that in nonmetastatic osteosarcoma of the extremity, conservative surgery in more than 90% and a good pathologic response rate of 50% can be expected with primary chemotherapy based on the MAP regimen. The response and resection rates in the ISG/OS-Oss study are in the same range as those of the previous study, whereas the event-free survival is lower than that previously achieved. Since the only difference between the two studies was the cumulative dose of postoperatively given MTX, our data support the importance of the cumulative dose of MTX in the MAP regimen.

Glucocorticoid exposure and fracture risk in a cohort of US patients with selected conditions.

PubMed

Balasubramanian, A; Wade, S W; Adler, R A; Saag, K; Pannacciulli, N; Curtis, J R

2018-06-20

We evaluated systemic glucocorticoid exposure and fracture among patients with newly-diagnosed inflammatory and immune-modulated conditions. Using administrative data, inception cohorts of RA, asthma/COPD, IBD, MS, lupus, and sarcoidosis patients age 18-64 years with benefits coverage ≥12 months before diagnosis (1/1/2005-12/31/2012) were followed to clinical fracture, cancer diagnosis, or 12/31/2012. Glucocorticoid users were new to therapy. Fracture incidence rates (IR) per 1,000 person-years were stratified by prednisone equivalent doses. Cox's proportional hazards models assessed risk by daily and cumulative dose, and by time since discontinuation, adjusted for baseline characteristics. Most patients (72% of 403,337) had glucocorticoid exposure; 52% were under age 50. IR (95% confidence intervals [CI]) of any osteoporotic fracture was elevated at doses < 5 mg/day, IR: 9.33 [7.29, 11.77] versus 0 mg/day, IR: 4.87 [4.72, 5.02]). Fracture rates were elevated at doses < 5 mg/day in patients < 50 years and those ≥ 50 years. In both age groups, fracture risk increased with increasing cumulative exposure, being approximately 2.5-fold higher at cumulative dose ≥ 5400 mg compared to < 675 mg. At ≥ 5400 mg, IR were 5.69 [4.32, 7.35] in patients < 50 years and 17.10 [14.97, 19.46] in older patients. Fracture risk decreased significantly within months following glucocorticoid discontinuation. In patients with a variety of inflammatory conditions, fracture risk increased at doses as low as < 5 mg/day. Risk increased with increasing cumulative exposure and decreased soon following glucocorticoid discontinuation. Trends were similar between patients older and younger than 50 years. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

γ-H2AX/53BP1/pKAP-1 foci and their linear tracks induced by in vitro exposure to radon and its progeny in human peripheral blood lymphocytes

PubMed Central

Ding, Defang; Zhang, Yaping; Wang, Jing; Wang, Xufei; Fan, Dunhuang; He, Linfeng; Zhang, Xuxia; Gao, Yun; Li, Qiang; Chen, Honghong

2016-01-01

The biodosimetric information is critical for evaluating the human health hazards caused by radon and its progeny. Here, we demonstrated that the formation of phosphorylated histone variant H2AX (γ-H2AX), p53-binding protein 1 (53BP1) and phosphorylated KRAB-associated protein 1 (pKAP-1) foci and their linear tracks in human peripheral blood lymphocytes (HPBLs) in vitro exposed to radon and its progeny were dependent on the cumulative absorbed dose of radon exposure but was unrelated to the concentration of radon. Among them, γ-H2AX foci and its linear tracks were the most sensitive indicators with the lowest estimable cumulative absorbed dose of 1.74 mGy from their linear dose-response curves and sustained for 12 h after termination of radon exposure. In addition, three types of foci showed an overdispersed non-Poisson distribution in HPBLs. The ratios of pKAP-1/γ-H2AX foci co-localization, 53BP1/γ-H2AX foci co-localization and 53BP1/pKAP-1 foci co-localization were significantly increased in HPBLs exposed to radon while they were unrelated to the cumulative dose of radon exposure, suggesting that γ-H2AX, pKAP-1 and 53BP1 play an important role in the repair of heterochromatic double-strand breaks. Altogether, our findings provide an experimental basis for estimating the biological dose of internal α-particle irradiation from radon and its progeny exposure in humans. PMID:27922110

Cumulative radiation dose caused by radiologic studies in critically ill trauma patients.

PubMed

Kim, Patrick K; Gracias, Vicente H; Maidment, Andrew D A; O'Shea, Michael; Reilly, Patrick M; Schwab, C William

2004-09-01

Critically ill trauma patients undergo many radiologic studies, but the cumulative radiation dose is unknown. The purpose of this study was to estimate the cumulative effective dose (CED) of radiation resulting from radiologic studies in critically ill trauma patients. The study group was composed of trauma patients at an urban Level I trauma center with surgical intensive care unit length of stay (LOS) greater than 30 days. The radiology records were reviewed. A typical effective dose per study for each type of plain film radiograph, computed tomographic scan, fluoroscopic study, and nuclear medicine study was used to calculate CED. Forty-six patients met criteria. The mean surgical intensive care unit and hospital LOS were 42.7 +/- 14.0 and 59.5 +/- 28.5 days, respectively. The mean Injury Severity Score was 32.2 +/- 15.0. The mean number of studies per patient was 70.1 +/- 29.0 plain film radiographs, 7.8 +/- 4.1 computed tomographic scans, 2.5 +/- 2.6 fluoroscopic studies, and 0.065 +/- 0.33 nuclear medicine study. The mean CED was 106 +/- 59 mSv per patient (range, 11-289 mSv; median, 104 mSv). Among age, mechanism, Injury Severity Score, and LOS, there was no statistically significant predictor of high CED. The mean CED in the study group was 30 times higher than the average yearly radiation dose from all sources for individuals in the United States. The theoretical additional morbidity attributable to radiologic studies was 0.78%. From a radiobiologic perspective, risk-to-benefit ratios of radiologic studies are favorable, given the importance of medical information obtained. Current practice patterns regarding use of radiologic studies appear to be acceptable.

Effect of gamma radiation on native endolithic microorganisms from a radioactive waste deposit site.

PubMed

Pitonzo, B J; Amy, P S; Rudin, M

1999-07-01

A time-course experiment was conducted to evaluate the effects of gamma radiation on the indigenous microbiota present in rock obtained from Yucca Mountain, Nevada Test Site. Microcosms were constructed by placing pulverized Yucca Mountain rock in polystyrene cylinders. Continuous exposure (96 h) at a dose rate of 1.63 Gy/min was used to mimic the near-field environment surrounding waste canisters. The expected maximum surface dose rate from one unbreached canister designed to contain spent nuclear fuels is 0.06 Gy/min. Considering the current repository packing design, multiple canisters within one vault, the cumulative dose rate may well approach that used in this experiment. The microbial communities were characterized after receiving cumulative doses of 0, 0.098, 0. 58, 2.33, 4.67, 7.01 and 9.34 kGy. Radiation-resistant microorganisms in the pulverized rock became viable but nonculturable (VBNC) after a cumulative dose of 2.33 kGy. VBNC microorganisms lose the ability to grow on media on which they have routinely been cultured in response to the environmental stress imposed (i.e. radiation) but can be detected throughout the time course using direct fluorescence microscopy techniques. Two representative exopolysaccharide-producing isolates from Yucca Mountain were exposed to the same radiation regimen in sand microcosms. One isolate was much more radiation-resistant than the other, but both had greater resistance than the general microbial community based on culturable counts. However, when respiring cell counts (VBNC) were compared after irradiation, the results would indicate much more radiation resistance of the individual isolates and the microbial community in general. These results have significant implications for underground storage of nuclear waste as they indicate that indigenous microorganisms are capable of surviving gamma irradiation in a VBNC state.

Predicted cumulative dose to firefighters and the offsite public from natural and anthropogenic radionuclides in smoke from wildland fires at the Savannah River Site, South Carolina USA.

PubMed

Viner, Brian J; Jannik, Tim; Hepworth, Allan; Adetona, Olorunfemi; Naeher, Luke; Eddy, Teresa; Doman, Eric; Blake, John

2018-02-01

The contaminated ground surface at Savannah River Site (SRS) is a result of the decades of work that has been performed maintaining the country's nuclear stockpile and performing research and development on nuclear materials. The volatilization of radionuclides during wildfire results in airborne particles that are dispersed within the smoke plume and may result in doses to downwind firefighters and the public. To better understand the risk that these smoke plumes present, we have characterized four regions at SRS in terms of their fuel characteristics and radiological contamination on the ground. Combined with general meteorological conditions describing typical and extreme burn conditions, we have simulated potential fires in these regions and predicted the potential radiological dose that could be received by firefighting personnel and the public surrounding the SRS. In all cases, the predicted cumulative dose was a small percent of the US Department of Energy regulatory limit (0.25 mSv). These predictions were conservative and assumed that firefighters would be exposed for the duration of their shift and the public would be exposed for the entire day over the duration of the burn. Realistically, firefighters routinely rotate off the firefront during their shift and the public would likely remain indoors much of the day. However, we show that even under worst-case conditions the regulatory limits are not exceeded. We can infer that the risks associated with wildfires would not be expected to cause cumulative doses above the level of concern to either responding personnel or the offsite public. Copyright © 2017 Elsevier Ltd. All rights reserved.

Predicted cumulative dose to firefighters and the offsite public from natural and anthropogenic radionuclides in smoke from wildland fires at the Savannah River Site, South Carolina USA

DOE PAGES

Viner, Brian J.; Jannik, Tim; Hepworth, Allan; ...

2017-11-22

The contaminated ground surface at Savannah River Site (SRS) is a result of the decades of work that has been performed maintaining the country's nuclear stockpile and performing research and development on nuclear materials. The volatilization of radionuclides during wildfire results in airborne particles that are dispersed within the smoke plume and may result in doses to downwind firefighters and the public. To better understand the risk that these smoke plumes present, we have characterized four regions at SRS in terms of their fuel characteristics and radiological contamination on the ground. Combined with general meteorological conditions describing typical and extrememore » burn conditions, we have simulated potential fires in these regions and predicted the potential radiological dose that could be received by firefighting personnel and the public surrounding the SRS. In all cases, the predicted cumulative dose was a small percent of the US Department of Energy regulatory limit (0.25 mSv). These predictions were conservative and assumed that firefighters would be exposed for the duration of their shift and the public would be exposed for the entire day over the duration of the burn. Realistically, firefighters routinely rotate off the firefront during their shift and the public would likely remain indoors much of the day. However, we show that even under worst-case conditions the regulatory limits are not exceeded. In conclusion, we can infer that the risks associated with wildfires would not be expected to cause cumulative doses above the level of concern to either responding personnel or the offsite public.« less

Predicted cumulative dose to firefighters and the offsite public from natural and anthropogenic radionuclides in smoke from wildland fires at the Savannah River Site, South Carolina USA

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

Viner, Brian J.; Jannik, Tim; Hepworth, Allan

The contaminated ground surface at Savannah River Site (SRS) is a result of the decades of work that has been performed maintaining the country's nuclear stockpile and performing research and development on nuclear materials. The volatilization of radionuclides during wildfire results in airborne particles that are dispersed within the smoke plume and may result in doses to downwind firefighters and the public. To better understand the risk that these smoke plumes present, we have characterized four regions at SRS in terms of their fuel characteristics and radiological contamination on the ground. Combined with general meteorological conditions describing typical and extrememore » burn conditions, we have simulated potential fires in these regions and predicted the potential radiological dose that could be received by firefighting personnel and the public surrounding the SRS. In all cases, the predicted cumulative dose was a small percent of the US Department of Energy regulatory limit (0.25 mSv). These predictions were conservative and assumed that firefighters would be exposed for the duration of their shift and the public would be exposed for the entire day over the duration of the burn. Realistically, firefighters routinely rotate off the firefront during their shift and the public would likely remain indoors much of the day. However, we show that even under worst-case conditions the regulatory limits are not exceeded. In conclusion, we can infer that the risks associated with wildfires would not be expected to cause cumulative doses above the level of concern to either responding personnel or the offsite public.« less

TEDE per cumulated activity for family members exposed to adult patients treated with 131I.

PubMed

Han, Eun Young; Lee, Choonsik; Bolch, Wesley E

2013-01-01

In 1997, the United States Nuclear Regulatory Commission amended its criteria under which patients administered radioactive materials could be released from the hospital. The revised criteria ensures that the total effective dose equivalent (TEDE) to any individual exposed to the released patient will not likely exceed 5 mSv. Licensees are recommended to use one of the three options to release the patient in accordance with these regulatory requirements: administered activity, measured dose rate, or patient-specific dose calculation. The NRC's suggested calculation method is based on the assumption that the patient (source) and a family member (target) are each considered to be points in space. This point source/target assumption has been shown to be conservative in comparison to more realistic guidelines. In this present study, the effective doses to family members were calculated using a series of revised Oak Ridge National Laboratory stylised phantoms coupled with a Monte Carlo radiation transport code. A set of TEDE per cumulated activity values were calculated for three different distributions of (131)I (thyroid, abdomen and whole body), various separation distances and two exposure scenarios (face-to-face standing and side-by-side lying). The results indicate that an overestimation of TEDE per cumulated activity based on the point source/target method was >2-fold. The values for paediatric phantoms showed a strong age-dependency, which showed that dosimetry for children should be separately considered instead of using adult phantoms as a substitute. On the basis of the results of this study, a licensee may use less conservative patient-specific release criteria and provide the patient and the family members with more practical dose avoidance guidelines.

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

Iwai, P; Lins, L Nadler

Purpose: There is a lack of studies with significant cohort data about patients using pacemaker (PM), implanted cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) device undergoing radiotherapy. There is no literature comparing the cumulative doses delivered to those cardiac implanted electronic devices (CIED) calculated by different algorithms neither studies comparing doses with heterogeneity correction or not. The aim of this study was to evaluate the influence of the algorithms Pencil Beam Convolution (PBC), Analytical Anisotropic Algorithm (AAA) and Acuros XB (AXB) as well as heterogeneity correction on risk categorization of patients. Methods: A retrospective analysis of 19 3DCRT ormore » IMRT plans of 17 patients was conducted, calculating the dose delivered to CIED using three different calculation algorithms. Doses were evaluated with and without heterogeneity correction for comparison. Risk categorization of the patients was based on their CIED dependency and cumulative dose in the devices. Results: Total estimated doses at CIED calculated by AAA or AXB were higher than those calculated by PBC in 56% of the cases. In average, the doses at CIED calculated by AAA and AXB were higher than those calculated by PBC (29% and 4% higher, respectively). The maximum difference of doses calculated by each algorithm was about 1 Gy, either using heterogeneity correction or not. Values of maximum dose calculated with heterogeneity correction showed that dose at CIED was at least equal or higher in 84% of the cases with PBC, 77% with AAA and 67% with AXB than dose obtained with no heterogeneity correction. Conclusion: The dose calculation algorithm and heterogeneity correction did not change the risk categorization. Since higher estimated doses delivered to CIED do not compromise treatment precautions to be taken, it’s recommend that the most sophisticated algorithm available should be used to predict dose at the CIED using heterogeneity correction.« less

A cumulative dose comparison between salbutamol and fenoterol metered dose aerosols in asthmatic patients.

PubMed Central

Bellamy, D.; Penketh, A.

1987-01-01

The potency and side effects of salbutamol and fenoterol inhalers have been compared in 8 asthmatic patients using a dose response curve. There was no significant difference in the absolute or percentage increase in FEV1 with the two treatments, but fenoterol caused a significantly greater (P less than 0.01) increase in heart rate than did salbutamol. A greater degree of bronchodilatation was observed with increased doses and we suggest that regular higher doses may provide better bronchodilatation and control of asthma in selected patients. PMID:3432172

Relative resistance of Pacific salmon to infectious salmon anaemia virus

USGS Publications Warehouse

Rolland, J.B.; Winton, J.R.

2003-01-01

Infectious salmon anaemia (ISA) is a major disease of Atlantic salmon, Salmo salar, caused by an orthomyxovirus (ISAV). Increases in global aqua culture and the international movement of fish made it important to determine if Pacific salmon are at risk. Steelhead trout, Oncorhynchus mykiss, and chum, O. keta, Chinook, O. tshawytscha, coho, O. kisutch, and Atlantic salmon were injected intraperitoneally with a high, medium, or low dose of a Norwegian strain of ISAV. In a second challenge, the same species, except chum salmon, were injected with a high dose of either a Canadian or the Norwegian strain. Average cumulative mortality of Atlantic salmon in trial 1 was 12% in the high dose group, 20% in the medium dose group and 16% in the low dose group. The average cumulative mortality of Atlantic salmon in trial 2 was 98%. No signs typical of ISA and no ISAV-related mortality occurred among any of the groups of Oncorhynchus spp. in either experiment, although ISAV was reisolated from some fish sampled at intervals post-challenge. The results indicate that while Oncorhynchus spp. are quite resistant to ISAV relative to Atlantic salmon, the potential for ISAV to adapt to Oncorhynchus spp. should not be ignored.

Cumulative trauma and posttraumatic stress disorder among children exposed to the 9/11 World Trade Center attack.

PubMed

Mullett-Hume, Elizabeth; Anshel, Daphne; Guevara, Vivianne; Cloitre, Marylene

2008-01-01

Two and one-half years after the September 11, 2001 World Trade Center attack, 204 middle school students in an immigrant community located near Ground Zero were assessed for posttraumatic stress disorder (PTSD) symptoms as influenced by "dose" of exposure to the attack and accumulated lifetime traumas. Ninety percent of students reported at least one traumatic event other than 9/11 (e.g., community violence) with an average of 4 lifetime events reported. An interaction was obtained such that the dose-response effect depended on presence of other traumas. Among students with the lowest number of additional traumas, the usual dose-response pattern of increasing PTSD symptoms with increasing 9/11 exposure was observed; among those with medium to high cumulative life trauma, PTSD symptoms were substantially higher and uniformly so regardless of 9/11 exposure dose. Results suggest that traumas that precede or follow mass violence often have as much as if not greater impact on long-term symptom severity than high-dose exposure to the event. Implications regarding the presence of continuing or previous trauma exposure for postdisaster and early intervention policies are discussed. (c) 2008 APA, all rights reserved

A U.S. Multicenter Study of Recorded Occupational Radiation Badge Doses in Nuclear Medicine.

PubMed

Villoing, Daphnée; Yoder, R Craig; Passmore, Christopher; Bernier, Marie-Odile; Kitahara, Cari M

2018-05-01

Purpose To summarize occupational badge doses recorded for a sample of U.S. nuclear medicine technologists. Materials and Methods Nine large U.S. medical institutions identified 208 former and current nuclear medicine technologists certified after 1979 and linked these individuals to historic badge dose records maintained by a commercial dosimetry company (Landauer), yielding a total of 2618 annual dose records. The distributions of annual and cumulative occupational doses were described by using summary statistics. Results Between 1992 and 2015, the median annual personal dose equivalent per nuclear medicine technologist was 2.18 mSv (interquartile range [IQR], 1.25-3.47 mSv; mean, 2.69 mSv). Median annual personal dose equivalents remained relatively constant over this period (range, 1.40-3.30 mSv), while maximum values generally increased over time (from 8.00 mSv in 1992 to 13.9 mSv in 2015). The median cumulative personal dose equivalent was 32.9 mSv (IQR, 18.1-65.5 mSv; mean, 51.4 mSv) for 45 technologists who had complete information and remained employed through 2015. Conclusion Occupational radiation doses were well below the established occupational limits and were consistent with those observed for nuclear medicine technologists worldwide and were greater than those observed for nuclear and general medical workers in the United States These results should be informative for radiation monitoring and safety efforts in nuclear medicine departments. © RSNA, 2018 Online supplemental material is available for this article.

Hypofractionated Proton Boost Combined with External Beam Radiotherapy for Treatment of Localized Prostate Cancer

PubMed Central

Johansson, Silvia; Åström, Lennart; Sandin, Fredrik; Isacsson, Ulf; Montelius, Anders; Turesson, Ingela

2012-01-01

Proton boost of 20 Gy in daily 5 Gy fractions followed by external beam radiotherapy (EBRT) of 50 Gy in daily 2 Gy fractions were given to 278 patients with prostate cancer with T1b to T4N0M0 disease. Fifty-three percent of the patients received neoadjuvant androgen deprivation therapy (N-ADT). The medium followup was 57 months. The 5-year PSA progression-free survival was 100%, 95%, and 74% for low-, intermediate-, and high-risk patients, respectively. The toxicity evaluation was supported by a patient-reported questionnaire before every consultant visit. Cumulative probability and actuarial prevalence of genitourinary (GU) and gastrointestinal (GI) toxicities are presented according to the RTOG classification. N-ADT did not influence curability. Mild pretreatment GU-symptoms were found to be a strong predictive factor for GU-toxicity attributable to treatment. The actuarial prevalence declined over 3 to 5 years for both GU and GI toxicities, indicating slow resolution of epithelial damage to the genitourinary and gastrointestinal tract. Bladder toxicities rather than gastrointestinal toxicities seem to be dose limiting. More than 5-year followup is necessary to reveal any sign of true progressive late side effects of the given treatment. Hypofractionated proton-boost combined with EBRT is associated with excellent curability of localized PC and acceptable frequencies of treatment toxicity. PMID:22848840

Reducing risk of Anthracycline-related heart failure after childhood cancer | Division of Cancer Prevention

Cancer.gov

Childhood cancer survivors are at a 15-fold risk of developing heart failure (HF) compared to age-matched controls. There is a strong dose-dependent association between anthracyclines and risk of HF; the incidence approaches 20% at cumulative doses between 300-600 mg/m2, and exceeds 30% for doses >600 mg/m2. Outcome following HF is poor; 5-year survival rate is |

ANALYSIS OF EPR AND FISH STUDIES OF RADIATION DOSES IN PERSONS WHO LIVED IN THE UPPER REACHES OF THE TECHA RIVER

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

Degteva, M. O.; Shagina, N. B.; Shishkina, Elena A.

Waterborne radioactive releases into the Techa River from the Mayak Production Association in Russia during 1949–1956 resulted in significant doses to about 30,000 persons who lived in downstream settlements. The residents were exposed to internal and external radiation. Two methods for reconstruction of the external dose are considered in this paper, electron paramagnetic resonance (EPR) measurements of teeth and fluorescence in situ hybridization (FISH) measurements of chromosome translocations in circulating lymphocytes. The main issue in the application of the EPR and FISH methods for reconstruction of the external dose for the Techa Riverside residents was strontium radioisotopes incorporated in teethmore » and bones that served as a source of confounding local exposures. In order to estimate and subtract doses from incorporated 89,90Sr, the EPR and FISH assays were supported by measurements of 90Sr-body burdens and estimates of 90Sr concentrations in dental tissues by the luminescence method. The resulting dose estimates derived from EPR and FISH measurements for residents of the upper Techa River were found to be consistent: the mean values vary from 510 – 550 mGy for the villages located close to the site of radioactive release to 130 – 160 mGy for the more distant villages. The upper bound of individual estimates for both methods is equal to 2.2 – 2.3 Gy. The EPR- and FISH-based dose estimates were compared with the doses calculated for the donors using the Techa River Dosimetry System (TRDS). The TRDS external dose assessments were based on the data on contamination of the Techa River floodplain, simulation of ai r kerma above the contaminated soil, age-dependent life-styles and individual residence histories. For correct comparison TRDS-based doses were calculated from two sources: external exposure from the contaminated environment and internal exposure from 137Cs incorporated in donors’ soft tissues. The TRDS-based absorbed doses in tooth enamel and muscle were in agreement with with EPR- and FISH-based estimates within uncertainty bounds. Basically, the agreement between the estimates has confirmed the validity of external doses calculated with the Techa River Dosimetry System.« less

External radiation dose and cancer mortality among French nuclear workers: considering potential confounding by internal radiation exposure.

PubMed

Fournier, L; Laurent, O; Samson, E; Caër-Lorho, S; Laroche, P; Le Guen, B; Laurier, D; Leuraud, K

2016-11-01

French nuclear workers have detailed records of their occupational exposure to external radiation that have been used to examine associations with subsequent cancer mortality. However, some workers were also exposed to internal contamination by radionuclides. This study aims to assess the potential for bias due to confounding by internal contamination of estimates of associations between external radiation exposure and cancer mortality. A cohort of 59,004 workers employed for at least 1 year between 1950 and 1994 by CEA (Commissariat à l'Energie Atomique), AREVA NC, or EDF (Electricité de France) and badge-monitored for external radiation exposure were followed through 2004 to assess vital status and cause of death. A flag based on a workstation-exposure matrix defined four levels of potential for internal contamination. Standardized mortality ratios were assessed for each level of the internal contamination indicator. Poisson regression was used to quantify associations between external radiation exposure and cancer mortality, adjusting for potential internal contamination. For solid cancer, the mortality deficit tended to decrease as the levels of potential for internal contamination increased. For solid cancer and leukemia excluding chronic lymphocytic leukemia, adjusting the dose-response analysis on the internal contamination indicator did not markedly change the excess relative risk per Sievert of external radiation dose. This study suggests that in this cohort, neglecting information on internal dosimetry while studying the association between external dose and cancer mortality does not generate a substantial bias. To investigate more specifically the health effects of internal contamination, an effort is underway to estimate organ doses due to internal contamination.

No dose-dependent increase in fracture risk after long-term exposure to high doses of retinol or beta-carotene.

PubMed

Ambrosini, G L; Bremner, A P; Reid, A; Mackerras, D; Alfonso, H; Olsen, N J; Musk, A W; de Klerk, N H

2013-04-01

Uncertainty remains over whether or not high intakes of retinol or vitamin A consumed through food or supplements may increase fracture risk. This intervention study found no increase in fracture risk among 2,322 adults who took a controlled, high-dose retinol supplement (25,000 IU retinyl palmitate/day) for as long as 16 years. There was some evidence that beta-carotene supplementation decreased fracture risk in men. There is conflicting epidemiological evidence regarding high intakes of dietary or supplemental retinol and an increased risk for bone fracture. We examined fracture risk in a study administering high doses of retinol and beta-carotene (BC) between 1990 and 2007. The Vitamin A Program was designed to test the efficacy of retinol and BC supplements in preventing malignancies in persons previously exposed to blue asbestos. Participants were initially randomised to 7.5 mg retinol equivalents (RE)/day as retinyl palmitate, 30 mg/day BC or 0.75 mg/day BC from 1990 to 1996; after which, all participants received 7.5 mg RE/day. Fractures were identified by questionnaire and hospital admission data up until 2006. Risk of any fracture or osteoporotic fracture according to cumulative dose of retinol and BC supplementation was examined using conditional logistic regression models adjusting for age, sex, smoking, body mass index, medication use and previous fracture. Supplementation periods ranged from 1 to 16 years. Of the 2,322 (664 females and 1,658 males) participants, 187 experienced 237 fractures. No associations were observed between cumulative dose of retinol and risk for any fracture (OR per 10 g RE=0.83; 95% CI, 0.63-1.08) or osteoporotic fracture (OR per 10 g RE=0.95; 95% CI 0.64-1.40). Among men, cumulative dose of BC was associated with a slightly reduced risk of any fracture (OR per 10 g=0.89; 95% CI 0.81-0.98) and osteoporotic fracture (OR per 10 g=0.84; 95% CI 0.72-0.97). This study observed no increases in fracture risk after long-term supplementation with high doses of retinol and/or beta-carotene.

USE OF PBPK MODELS FOR ASSESSING ABSORBED DOSE AND CHE INHIBITION FROM AGGREGATE EXPOSURE OF INFANTS AND CHILDREN TO ORGANOPHOSPHORUS INSECTICIDES

EPA Science Inventory

A physiological pharmacokinetic (PBPK) modeling framework has been established to assess cumulative risk of dose and injury of infants and children to organophosphorus (OP) insecticides from aggregate sources and routes. Exposure inputs were drawn from all reasonable sources, pr...

Effect of age on the incidence of aseptic meningitis following immunization with monovalent mumps vaccine.

PubMed

Muta, Hiromi; Nagai, Takao; Ito, Yuhei; Ihara, Toshiaki; Nakayama, Tetsuo

2015-11-09

The purpose of this study was to determine the risk of aseptic meningitis after mumps vaccination in younger children compared with older children. This prospective cohort study included a total of 21,465 children under 18 years of age who had received the first dose of three of the Japanese mumps monovalent vaccine. We compared the cumulative incidence of aseptic meningitis for 30 days after vaccination among the following age groups: ≤ 1, 2, 3-4, and ≥ 5 years old. We also investigated the cumulative incidence of salivary gland swelling, a fever (≥ 38°C) lasting at least 3 days during the 10 to 25 days following immunization, vomiting of 3 times or more, headache, and seizure. A total of 10 aseptic meningitis, 551 salivary gland swelling, 844 fevers, 669 vomiting, 757 headaches, and 29 seizure cases were identified. The cumulative incidence of aseptic meningitis increased with age (0.016%, 0.021%, 0.066%, and 0.096%, respectively). Statistical significance was observed between children ≥ 3 years old and those < 3 years of age [0.078% vs. 0.018%, RR 4.35 (95% CI 1.05-18.2), p=0.04]. The cumulative incidence of salivary gland swelling also increased with age (1.8%, 3.0%, 3.5%, and 4.5%, respectively). For non-specific adverse events, the cumulative incidence of fever or seizure decreased with age. In contrast, the cumulative incidence of headache increased with age. The cumulative incidence of vomiting was similar among children ≤ 4 years of age; however, that in those children ≥ 5 years old was significantly lower. The first dose of mumps vaccine that is currently available for use in Japan may be administered in children less than 3 years of age in order to complicate a less aseptic meningitis after immunization. Copyright © 2015 Elsevier Ltd. All rights reserved.

Low dose anti-thymocyte globulin reduces chronic graft-versus-host disease incidence rates after matched unrelated donor transplantation.

PubMed

Tandra, Anand; Covut, Fahrettin; Cooper, Brenda; Creger, Richard; Brister, Lauren; McQuigg, Bernadette; Caimi, Paolo; Malek, Ehsan; Tomlinson, Ben; Lazarus, Hillard M; Otegbeye, Folashade; Kolk, Merle; de Lima, Marcos; Metheny, Leland

2017-12-04

Anti-thymocyte globulin (ATG) is often added to hematopoietic stem cell transplant conditioning regimens to prevent graft rejection and reduce graft-versus-host disease (GVHD). Doses used in retrospective and prospective clinical trials have ranged from 2.5 to 20 mg/kg with rates of grade II-IV acute GVHD and chronic GVHD up to 40 and 60%, respectively. We retrospectively compared outcomes in recipients of matched unrelated donor (MUD) grafts given low dose rabbit ATG IV 3 mg/kg (n = 52) versus recipients of matched related donor (MRD) grafts (n = 48) without ATG. One year cumulative incidence of chronic GVHD was 25.2% in the MUD group versus 33.3% in the MRD group (p = .5). One-year cumulative incidence of extensive chronic GVHD was 9.6% in the MUD group versus 26.6% in the MRD group (p = .042). Our analysis supports the use of low dose ATG in MUD transplantation as an effective therapy to prevent chronic GVHD.

Caffeine is a risk factor for osteopenia of prematurity in preterm infants: a cohort study.

PubMed

Ali, Ebtihal; Rockman-Greenberg, Cheryl; Moffatt, Michael; Narvey, Michael; Reed, Martin; Jiang, Depeng

2018-01-22

Caffeine, the most commonly used medication in Neonatal Intensive Care Units, has calciuric and osteoclastogenic effects. To examine the association between the cumulative dose and duration of therapy of caffeine and osteopenia of prematurity, a retrospective cohort study was conducted including premature infants less than 31 weeks and birth weight less than 1500 g. Osteopenia of prematurity was evaluated using chest X-rays on a biweekly basis over 12 weeks of hospitalization. The cohort included 109 infants. 51% had osteopenia of prematurity and 8% had spontaneous rib fractures. Using the generalized linear mixed model, caffeine dose and duration of caffeine therapy showed a strong association with osteopenia of prematurity. Steroids and vitamin D were also significantly correlated with osteopenia of prematurity while diuretic use did not show a statistically significant effect. The cumulative dose and duration of therapy of caffeine, as well as steroid are associated with osteopenia of prematurity in this cohort. Future studies are needed to confirm these findings and determine the lowest dose of caffeine needed to treat effectively apnea of prematurity.

Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study

PubMed Central

Pearce, Mark S; Salotti, Jane A; Little, Mark P; McHugh, Kieran; Lee, Choonsik; Kim, Kwang Pyo; Howe, Nicola L; Ronckers, Cecile M; Rajaraman, Preetha; Craft, Alan W; Parker, Louise; de González, Amy Berrington

2012-01-01

Summary Background Although CT scans are very useful clinically, potential cancer risks exist from associated ionising radiation, in particular for children who are more radiosensitive than adults. We aimed to assess the excess risk of leukaemia and brain tumours after CT scans in a cohort of children and young adults. Methods In our retrospective cohort study, we included patients without previous cancer diagnoses who were first examined with CT in National Health Service (NHS) centres in England, Wales, or Scotland (Great Britain) between 1985 and 2002, when they were younger than 22 years of age. We obtained data for cancer incidence, mortality, and loss to follow-up from the NHS Central Registry from Jan 1, 1985, to Dec 31, 2008. We estimated absorbed brain and red bone marrow doses per CT scan in mGy and assessed excess incidence of leukaemia and brain tumours cancer with Poisson relative risk models. To avoid inclusion of CT scans related to cancer diagnosis, follow-up for leukaemia began 2 years after the first CT and for brain tumours 5 years after the first CT. Findings During follow-up, 74 of 178 604 patients were diagnosed with leukaemia and 135 of 176 587 patients were diagnosed with brain tumours. We noted a positive association between radiation dose from CT scans and leukaemia (excess relative risk [ERR] per mGy 0·036, 95% CI 0·005–0·120; p=0·0097) and brain tumours (0·023, 0·010–0·049; p<0·0001). Compared with patients who received a dose of less than 5 mGy, the relative risk of leukaemia for patients who received a cumulative dose of at least 30 mGy (mean dose 51·13 mGy) was 3·18 (95% CI 1·46–6·94) and the relative risk of brain cancer for patients who received a cumulative dose of 50–74 mGy (mean dose 60·42 mGy) was 2·82 (1·33–6·03). Interpretation Use of CT scans in children to deliver cumulative doses of about 50 mGy might almost triple the risk of leukaemia and doses of about 60 mGy might triple the risk of brain cancer. Because these cancers are relatively rare, the cumulative absolute risks are small: in the 10 years after the first scan for patients younger than 10 years, one excess case of leukaemia and one excess case of brain tumour per 10 000 head CT scans is estimated to occur. Nevertheless, although clinical benefits should outweigh the small absolute risks, radiation doses from CT scans ought to be kept as low as possible and alternative procedures, which do not involve ionising radiation, should be considered if appropriate. Funding US National Cancer Institute and UK Department of Health. PMID:22681860

Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study.

PubMed

Pearce, Mark S; Salotti, Jane A; Little, Mark P; McHugh, Kieran; Lee, Choonsik; Kim, Kwang Pyo; Howe, Nicola L; Ronckers, Cecile M; Rajaraman, Preetha; Sir Craft, Alan W; Parker, Louise; Berrington de González, Amy

2012-08-04

Although CT scans are very useful clinically, potential cancer risks exist from associated ionising radiation, in particular for children who are more radiosensitive than adults. We aimed to assess the excess risk of leukaemia and brain tumours after CT scans in a cohort of children and young adults. In our retrospective cohort study, we included patients without previous cancer diagnoses who were first examined with CT in National Health Service (NHS) centres in England, Wales, or Scotland (Great Britain) between 1985 and 2002, when they were younger than 22 years of age. We obtained data for cancer incidence, mortality, and loss to follow-up from the NHS Central Registry from Jan 1, 1985, to Dec 31, 2008. We estimated absorbed brain and red bone marrow doses per CT scan in mGy and assessed excess incidence of leukaemia and brain tumours cancer with Poisson relative risk models. To avoid inclusion of CT scans related to cancer diagnosis, follow-up for leukaemia began 2 years after the first CT and for brain tumours 5 years after the first CT. During follow-up, 74 of 178,604 patients were diagnosed with leukaemia and 135 of 176,587 patients were diagnosed with brain tumours. We noted a positive association between radiation dose from CT scans and leukaemia (excess relative risk [ERR] per mGy 0·036, 95% CI 0·005-0·120; p=0·0097) and brain tumours (0·023, 0·010-0·049; p<0·0001). Compared with patients who received a dose of less than 5 mGy, the relative risk of leukaemia for patients who received a cumulative dose of at least 30 mGy (mean dose 51·13 mGy) was 3·18 (95% CI 1·46-6·94) and the relative risk of brain cancer for patients who received a cumulative dose of 50-74 mGy (mean dose 60·42 mGy) was 2·82 (1·33-6·03). Use of CT scans in children to deliver cumulative doses of about 50 mGy might almost triple the risk of leukaemia and doses of about 60 mGy might triple the risk of brain cancer. Because these cancers are relatively rare, the cumulative absolute risks are small: in the 10 years after the first scan for patients younger than 10 years, one excess case of leukaemia and one excess case of brain tumour per 10,000 head CT scans is estimated to occur. Nevertheless, although clinical benefits should outweigh the small absolute risks, radiation doses from CT scans ought to be kept as low as possible and alternative procedures, which do not involve ionising radiation, should be considered if appropriate. US National Cancer Institute and UK Department of Health. Copyright © 2012 Elsevier Ltd. All rights reserved.

Assessment of radiation doses from residential smoke detectors that contain americium-241

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

O'Donnell, F.R.; Etnier, E.L.; Holton, G.A.

1981-10-01

External dose equivalents and internal dose commitments were estimated for individuals and populations from annual distribution, use, and disposal of 10 million ionization chamber smoke detectors that contain 110 kBq (3 ..mu..Ci) americium-241 each. Under exposure scenarios developed for normal distribution, use, and disposal using the best available information, annual external dose equivalents to average individuals were estimated to range from 4 fSv (0.4 prem) to 20 nSv (2 ..mu..rem) for total body and from 7 fSv to 40 nSv for bone. Internal dose commitments to individuals under post disposal scenarios were estimated to range from 0.006 to 80 ..mu..Svmore » (0.0006 to 8 mrem) to total body and from 0.06 to 800 ..mu..Sv to bone. The total collective dose (the sum of external dose equivalents and 50-year internal dose commitments) for all individuals involved with distribution, use, or disposal of 10 million smoke detectors was estimated to be about 0.38 person-Sv (38 person-rem) to total body and 00 ft/sup 2/).« less

A tracking system to calculate patient skin dose in real-time during neurointerventional procedures using a biplane x-ray imaging system.

PubMed

Rana, V K; Rudin, S; Bednarek, D R

2016-09-01

Neurovascular interventional procedures using biplane fluoroscopic imaging systems can lead to increased risk of radiation-induced skin injuries. The authors developed a biplane dose tracking system (Biplane-DTS) to calculate the cumulative skin dose distribution from the frontal and lateral x-ray tubes and display it in real-time as a color-coded map on a 3D graphic of the patient for immediate feedback to the physician. The agreement of the calculated values with the dose measured on phantoms was evaluated. The Biplane-DTS consists of multiple components including 3D graphic models of the imaging system and patient, an interactive graphical user interface, a data acquisition module to collect geometry and exposure parameters, the computer graphics processing unit, and functions for determining which parts of the patient graphic skin surface are within the beam and for calculating dose. The dose is calculated to individual points on the patient graphic using premeasured calibration files of entrance skin dose per mAs including backscatter; corrections are applied for field area, distance from the focal spot and patient table and pad attenuation when appropriate. The agreement of the calculated patient skin dose and its spatial distribution with measured values was evaluated in 2D and 3D for simulated procedure conditions using a PMMA block phantom and an SK-150 head phantom, respectively. Dose values calculated by the Biplane-DTS were compared to the measurements made on the phantom surface with radiochromic film and a calibrated ionization chamber, which was also used to calibrate the DTS. The agreement with measurements was specifically evaluated with variation in kVp, gantry angle, and field size. The dose tracking system that was developed is able to acquire data from the two x-ray gantries on a biplane imaging system and calculate the skin dose for each exposure pulse to those vertices of a patient graphic that are determined to be in the beam. The calculations are done in real-time with a typical graphic update time of 30 ms and an average vertex separation of 3 mm. With appropriate corrections applied, the Biplane-DTS was able to determine the entrance dose within 6% and the spatial distribution of the dose within 4% compared to the measurements with the ionization chamber and film for the SK150 head phantom. The cumulative dose for overlapping fields from both gantries showed similar agreement. The Biplane-DTS can provide a good estimate of the peak skin dose and cumulative skin dose distribution during biplane neurointerventional procedures. Real-time display of this information should help the physician manage patient dose to reduce the risk of radiation-induced skin injuries.

A tracking system to calculate patient skin dose in real-time during neurointerventional procedures using a biplane x-ray imaging system

PubMed Central

Rana, V. K.; Rudin, S.; Bednarek, D. R.

2016-01-01

Purpose: Neurovascular interventional procedures using biplane fluoroscopic imaging systems can lead to increased risk of radiation-induced skin injuries. The authors developed a biplane dose tracking system (Biplane-DTS) to calculate the cumulative skin dose distribution from the frontal and lateral x-ray tubes and display it in real-time as a color-coded map on a 3D graphic of the patient for immediate feedback to the physician. The agreement of the calculated values with the dose measured on phantoms was evaluated. Methods: The Biplane-DTS consists of multiple components including 3D graphic models of the imaging system and patient, an interactive graphical user interface, a data acquisition module to collect geometry and exposure parameters, the computer graphics processing unit, and functions for determining which parts of the patient graphic skin surface are within the beam and for calculating dose. The dose is calculated to individual points on the patient graphic using premeasured calibration files of entrance skin dose per mAs including backscatter; corrections are applied for field area, distance from the focal spot and patient table and pad attenuation when appropriate. The agreement of the calculated patient skin dose and its spatial distribution with measured values was evaluated in 2D and 3D for simulated procedure conditions using a PMMA block phantom and an SK-150 head phantom, respectively. Dose values calculated by the Biplane-DTS were compared to the measurements made on the phantom surface with radiochromic film and a calibrated ionization chamber, which was also used to calibrate the DTS. The agreement with measurements was specifically evaluated with variation in kVp, gantry angle, and field size. Results: The dose tracking system that was developed is able to acquire data from the two x-ray gantries on a biplane imaging system and calculate the skin dose for each exposure pulse to those vertices of a patient graphic that are determined to be in the beam. The calculations are done in real-time with a typical graphic update time of 30 ms and an average vertex separation of 3 mm. With appropriate corrections applied, the Biplane-DTS was able to determine the entrance dose within 6% and the spatial distribution of the dose within 4% compared to the measurements with the ionization chamber and film for the SK150 head phantom. The cumulative dose for overlapping fields from both gantries showed similar agreement. Conclusions: The Biplane-DTS can provide a good estimate of the peak skin dose and cumulative skin dose distribution during biplane neurointerventional procedures. Real-time display of this information should help the physician manage patient dose to reduce the risk of radiation-induced skin injuries. PMID:27587043

A tracking system to calculate patient skin dose in real-time during neurointerventional procedures using a biplane x-ray imaging system

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

Rana, V. K., E-mail: vkrana@buffalo.edu

Purpose: Neurovascular interventional procedures using biplane fluoroscopic imaging systems can lead to increased risk of radiation-induced skin injuries. The authors developed a biplane dose tracking system (Biplane-DTS) to calculate the cumulative skin dose distribution from the frontal and lateral x-ray tubes and display it in real-time as a color-coded map on a 3D graphic of the patient for immediate feedback to the physician. The agreement of the calculated values with the dose measured on phantoms was evaluated. Methods: The Biplane-DTS consists of multiple components including 3D graphic models of the imaging system and patient, an interactive graphical user interface, amore » data acquisition module to collect geometry and exposure parameters, the computer graphics processing unit, and functions for determining which parts of the patient graphic skin surface are within the beam and for calculating dose. The dose is calculated to individual points on the patient graphic using premeasured calibration files of entrance skin dose per mAs including backscatter; corrections are applied for field area, distance from the focal spot and patient table and pad attenuation when appropriate. The agreement of the calculated patient skin dose and its spatial distribution with measured values was evaluated in 2D and 3D for simulated procedure conditions using a PMMA block phantom and an SK-150 head phantom, respectively. Dose values calculated by the Biplane-DTS were compared to the measurements made on the phantom surface with radiochromic film and a calibrated ionization chamber, which was also used to calibrate the DTS. The agreement with measurements was specifically evaluated with variation in kVp, gantry angle, and field size. Results: The dose tracking system that was developed is able to acquire data from the two x-ray gantries on a biplane imaging system and calculate the skin dose for each exposure pulse to those vertices of a patient graphic that are determined to be in the beam. The calculations are done in real-time with a typical graphic update time of 30 ms and an average vertex separation of 3 mm. With appropriate corrections applied, the Biplane-DTS was able to determine the entrance dose within 6% and the spatial distribution of the dose within 4% compared to the measurements with the ionization chamber and film for the SK150 head phantom. The cumulative dose for overlapping fields from both gantries showed similar agreement. Conclusions: The Biplane-DTS can provide a good estimate of the peak skin dose and cumulative skin dose distribution during biplane neurointerventional procedures. Real-time display of this information should help the physician manage patient dose to reduce the risk of radiation-induced skin injuries.« less

Continuous 7-Days-A-Week External Beam Irradiation in Locally Advanced Cervical Cancer: Final Results of the Phase I/II Study

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

Serkies, Krystyna, E-mail: kserkies@wp.pl; Dziadziuszko, Rafal; Jassem, Jacek

2012-03-01

Purpose: To evaluate the feasibility and efficacy of definitive continuous 7-days-a-week pelvic irradiation without breaks between external beam radiotherapy and brachytherapy in locally advanced cervical cancer. Methods and Materials: Between November 1998 and December 1999, 30 patients with International Federation of Obstetrics and Gynecology Stage IIB or IIIB cervical cancer were included in a prospective Phase I/II study of continuous 7-days-a-week pelvic irradiation, to the total Manchester point B dose of 40.0-57.6 Gy. The first 13 patients (Group A) were given a daily tumor dose of 1.6 Gy, and the remaining 17 patients (Group B) were given 1.8 Gy. Onemore » or two immediate brachytherapy applications (point A dose 10-20 Gy, each) were performed in 28 cases. Results: Two patients did not complete the irradiation because of apparent early progression of disease during the irradiation. Eleven of the 28 evaluable patients (39%; 45% and 35% in Groups A and B, respectively) completed their treatment within the prescribed overall treatment time. Acute toxicity (including severe European Organisation for Research and Treatment of Cancer/Radiation Therapy Oncology Group Grade 3 and 4 effects in 40%) was experienced by 83% of patients and resulted in unplanned treatment interruptions in 40% of all patients (31% and 47% of patients in Groups A and B, respectively). Severe intestinal side effects occurred in 31% and 41% of Patients in Groups A and B, respectively (p = 0.71). The 5-year overall survival probability was 33%. Cancer recurrence occurred in 63% of patients: 20% inside and 57% outside the pelvis. Cumulative incidence of late severe bowel and urinary bladder toxicity at 24 months was 15%. Conclusion: Continuous irradiation in locally advanced cervical cancer is associated with a high incidence of severe acute toxicity, resulting in unplanned treatment interruptions. Late severe effects and survival after continuous radiotherapy do not substantially differ from those obtained with conventionally fractionated radiotherapy.« less

Incorporation of additional radionuclides and the external exposure pathway into the BECAMP (Basic Environmental Compliance and Monitoring Program) radiological assessment model

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

Ng, Yook C.; Rodean, H.C.; Anspaugh, L.R.

The Nevada Applied Ecology Group (NAEG) Model of transport and dose for transuranic radionuclides was modified and expanded for the analysis of radionuclides other than pure alpha-emitters. Doses from internal and external exposures were estimated for the inventories and soil distributions of the individual radionuclides quantified in Areas 2 and 4 of the Nevada Test Site (NTS). We found that the dose equivalents via inhalation to liver, lungs, bone marrow, and bone surface from the plutonium isotopes and /sup 241/Am, those via ingestion to bone marrow and bone surfaces from /sup 90/Sr, and those via ingestion to all the targetmore » organs from /sup 137/Cs were the highest from internal exposures. The effective dose equivalents from /sup 137/Cs, /sup 152/Eu, and /sup 154/Eu were the highest from the external exposures. The /sup 60/Co, /sup 152/Eu, /sup 154/Eu, and /sup 155/Eu dose estimates for external exposures greatly exceeded those for internal exposures. The /sup 60/Co, /sup 90/Sr, and /sup 137/Cs dose equivalents from internal exposures were underestimated due to the adoption of some of the foodchain parameter values originally selected for /sup 239/Pu. Nonetheless, the ingestion pathway contributed significantly to the dose estimates for /sup 90/Sr and /sup 137/Cs, but contributed very much less than external exposures to the dose estimates for /sup 60/Co. Therefore, the use of more appropriate values would not alter the identification of important radionuclides, pathways, target organs, and exposure modes in this analysis. 19 refs., 13 figs., 12 tabs.« less

Stereotactic body radiotherapy for stage I non-small-cell lung cancer using higher doses for larger tumors: results of the second study.

PubMed

Miyakawa, Akifumi; Shibamoto, Yuta; Baba, Fumiya; Manabe, Yoshihiko; Murai, Taro; Sugie, Chikao; Yanagi, Takeshi; Takaoka, Taiki

2017-09-11

Efficacy of stereotactic body radiotherapy (SBRT) in stage I non-small-cell lung cancer (NSCLC) has almost been established. In Japan, the protocol of 48 Gy in 4 fractions over 4 days has been most often employed, but higher doses may be necessary to control large tumors. Previously, we conducted a clinical study using SBRT for stage I NSCLC employing different doses depending on tumor diameter, which was closed in 2008. Thereafter, a new study employing higher doses has been conducted, which is reported here. The purpose of this study was to review the safety and effectiveness of the higher doses. We escalated the total dose for the improvement of local control for large tumors. In this study, 71 patients underwent SBRT between December 2008 and April 2014. Isocenter doses of 48, 50, and 52 Gy were administered for tumors with a longest diameter of < 1.5 cm, 1.5-3 cm, and > 3 cm, respectively. It was recommended to cover 95% of the PTV with at least 90% of the isocenter dose, and in all but one cases, 95% of the PTV received at least 80% of the prescribed dose. Treatments were delivered in 4 fractions, giving 2 fractions per week. SBRT was performed with 6-MV photons using 4 non-coplanar and 3 coplanar beams. The median follow-up period was 44 months for all patients and 61 months for living patients. Overall survival (OS) was 65%, progression-free survival (PFS) was 55%, and cumulative incidence of local recurrence (LR) was 15% at 5 years. The 5-year OS was 69% for 57 stage IA patients and 53% for 14 stage IB patients (p = 0.44). The 5-year PFS was 55 and 54%, respectively (p = 0.98). The 5-year cumulative incidence of LR was 11 and 31%, respectively (p = 0.09). The cumulative incidence of Grade ≥ 2 radiation pneumonitis was 25%. Our newer SBRT study yielded reasonable local control and overall survival and acceptable toxicity, but escalating the total dose did not lead to improved outcomes. UMIN000027231 , registered on 3 May 2017. Retrospectively registered.

Evaluation of an Alcohol Withdrawal Protocol and a Preprinted Order Set at a Tertiary Care Hospital

PubMed Central

Ng, Karen; Dahri, Karen; Chow, Ivy; Legal, Michael

2011-01-01

Background: Alcohol withdrawal protocols involving symptom-triggered administration of benzodiazepine have been established to reduce the duration of treatment and the cumulative benzodiazepine dose (relative to usual care). However, the effects of a protocol combining fixed-schedule and symptom-triggered benzodiazepine dosing are less clear. Objective: To assess the efficacy and safety of a combination fixed-scheduled and symptom-triggered benzodiazepine dosing protocol for alcohol withdrawal, relative to usual care, for medical inpatients at a tertiary care hospital. Methods: A chart review of admissions to the internal medicine service for alcohol withdrawal was conducted to compare treatment outcomes before (October 2005 to April 2007) and after (October 2007 to April 2009) implementation of the combination protocol. The primary outcome was duration of benzodiazepine treatment for alcohol withdrawal. The secondary outcomes were cumulative benzodiazepine dose administered, safety implications, and use of adjunctive medications. Results: A total of 159 patients met the inclusion criteria. Assessable data were available for 71 charts from the pre-implementation period and 72 charts from the post-implementation period. The median duration of benzodiazepine treatment was 91 h before implementation and 57 h after implementation (p < 0.001). Use of the protocol was also associated with a significant reduction in severe complications of alcohol withdrawal (50% versus 33%, p = 0.019), median cumulative benzodiazepine dose (in lorazepam equivalents) (20.0 mg versus 15.5 mg, p = 0.026), and use of adjunctive medications (65% versus 38%, p = 0.001). The incidence of serious adverse outcomes of treatment with benzodiazepines was not significantly different between the 2 groups. Conclusions: Implementation of an alcohol withdrawal protocol with a combination of fixed-schedule and symptom-triggered benzodiazepine dosing in a medical ward was associated with a shorter duration of benzodiazepine use and a lower incidence of severe complications of alcohol withdrawal. PMID:22479099

Salvage Radiation Therapy Dose Response for Biochemical Failure of Prostate Cancer After Prostatectomy—A Multi-Institutional Observational Study

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

Pisansky, Thomas M., E-mail: pisansky.thomas@mayo.edu; Agrawal, Shree; Hamstra, Daniel A.

Purpose: To determine whether a dose-response relationship exists for salvage radiation therapy (RT) of biochemical failure after prostatectomy for prostate cancer. Methods and Materials: Individual data from 1108 patients who underwent salvage RT at 10 academic centers were pooled. The cohort was enriched for selection criteria more likely associated with tumor recurrence in the prostate bed (margin positive and pre-RT prostate-specific antigen [PSA] level of ≤2.0 ng/mL) and without the confounding of planned androgen suppression. The cumulative incidence of biochemical failure and distant metastasis over time was computed, and competing risks hazard regression models were used to investigate the association betweenmore » potential predictors and these outcomes. The association of radiation dose with outcomes was the primary focus. Results: With a 65.2-month follow-up duration, the 5- and 10-year estimates of freedom from post-RT biochemical failure (PSA level >0.2 ng/mL and rising) was 63.5% and 49.8%, respectively, and the cumulative incidence of distant metastasis was 12.4% by 10 years. A Gleason score of ≥7, higher pre-RT PSA level, extraprostatic tumor extension, and seminal vesicle invasion were associated with worse biochemical failure and distant metastasis outcomes. A salvage radiation dose of ≥66.0 Gy was associated with a reduced cumulative incidence of biochemical failure, but not of distant metastasis. Conclusions: The use of salvage radiation doses of ≥66.0 Gy are supported by evidence presented in the present multicenter pooled analysis of individual patient data. The observational reporting method, limited sample size, few distant metastasis events, modest follow-up duration, and elective use of salvage therapy might have diminished the opportunity to identify an association between the radiation dose and this endpoint.« less

SU-C-207A-07: Cumulative 18F-FDG Uptake Histogram Relative to Radiation Dose Volume Histogram of Lung After IMRT Or PSPT and Their Association with Radiation Pneumonitis

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

Shusharina, N; Choi, N; Bortfeld, T

2016-06-15

Purpose: To determine whether the difference in cumulative 18F-FDG uptake histogram of lung treated with either IMRT or PSPT is associated with radiation pneumonitis (RP) in patients with inoperable stage II and III NSCLC. Methods: We analyzed 24 patients from a prospective randomized trial to compare IMRT (n=12) with vs. PSPT (n=12) for inoperable NSCLC. All patients underwent PET-CT imaging between 35 and 88 days post-therapy. Post-treatment PET-CT was aligned with planning 4D CT to establish a voxel-to-voxel correspondence between post-treatment PET and planning dose images. 18F-FDG uptake as a function of radiation dose to normal lung was obtained formore » each patient. Distribution of the standard uptake value (SUV) was analyzed using a volume histogram method. The image quantitative characteristics and DVH measures were correlated with clinical symptoms of pneumonitis. Results: Patients with RP were present in both groups: 5 in the IMRT and 6 in the PSPT. The analysis of cumulative SUV histograms showed significantly higher relative volumes of the normal lung having higher SUV uptake in the PSPT patients for both symptomatic and asymptomatic cases (VSUV=2: 10% for IMRT vs 16% for proton RT and VSUV=1: 10% for IMRT vs 23% for proton RT). In addition, the SUV histograms for symptomatic cases in PSPT patients exhibited a significantly longer tail at the highest SUV. The absolute volume of the lung receiving the dose >70 Gy was larger in the PSPT patients. Conclusion: 18F-FDG uptake – radiation dose response correlates with RP in both groups of patients by means of the linear regression slope. SUV is higher for the PSPT patients for both symptomatic and asymptomatic cases. Higher uptake after PSPT patients is explained by larger volumes of the lung receiving high radiation dose.« less

Reduced bone mineral density in Japanese premenopausal women with systemic lupus erythematosus treated with glucocorticoids.

PubMed

Banno, S; Matsumoto, Y; Naniwa, T; Hayami, Y; Sugiura, Y; Yoshinouchi, T; Ueda, R

2002-12-01

Abstract We evaluated bone mineral density (BMD) in Japanese female patients with systemic lupus erythematosus (SLE) and assessed the influence of the use of glucocorticoids. Lumbar BMD was measured by dual x-ray absorptiometry (DXA) in 60 premenopausal females who previously had been receiving glucocorticoid therapy. Therapeutic- and disease-related variables for SLE were analyzed and bone resorption or formation markers were measured. Osteoporosis was defined as a T-score below 2.5 SD by DXA; 12 patients (20%) showed osteoporosis, and 30 (50%) had osteopenia. Compared with the nonosteoporotic group (n = 48), the osteoporotic group (n = 12) had a significantly longer duration of glucocorticoid treatment (P = 0.01), a cumulative prednisolone dose (P = 0.002), and an SLE damage index (SLICC/ACR). There was no difference in the incidence of osteoporosis either with or without the previous use of methyl-prednisolone pulse or immunosuppressive drugs. There was a significant positive correlation between urinary type I collagen cross-linked N-telopeptides (NTx) and serum bone-specific alkaline phosphatase (BAP) (r = 0.404, P = 0.002), but these bone metabolic markers showed no difference between the osteoporotic and nonosteoporotic groups. A good significant negative correlation was shown between BMD and the cumulative glucocorticoid dose (r = -0.351, P = 0.007). Stepwise logistic regression analysis showed that the cumulative glucocorticoid intake was independently associated with osteoporosis. Glucocorticoid-induced osteoporosis was frequently observed in Japanese SLE patients, as in Caucasian populations. The cumulative glucocorticoid dose was associated with an increased risk for osteoporosis. Bone metabolic markers such as NTx and BAP were not influenced by glucocorticoid treatment and could not predict current osteoporosis in SLE patients.

Comparison of two indices of exposure to polycyclic aromatic hydrocarbons in a retrospective aluminium smelter cohort.

PubMed

Friesen, Melissa C; Demers, Paul A; Spinelli, John J; Lorenzi, Maria F; Le, Nhu D

2007-04-01

The association between coal tar-derived substances, a complex mixture of polycyclic aromatic hydrocarbons, and cancer is well established. However, the specific aetiological agents are unknown. To compare the dose-response relationships for two common measures of coal tar-derived substances, benzene-soluble material (BSM) and benzo(a)pyrene (BaP), and to evaluate which among these is more strongly related to the health outcomes. The study population consisted of 6423 men with > or =3 years of work experience at an aluminium smelter (1954-97). Three health outcomes identified from national mortality and cancer databases were evaluated: incidence of bladder cancer (n = 90), incidence of lung cancer (n = 147) and mortality due to acute myocardial infarction (AMI, n = 184). The shape, magnitude and precision of the dose-response relationships and cumulative exposure levels for BSM and BaP were evaluated. Two model structures were assessed, where 1n(relative risk) increased with cumulative exposure (log-linear model) or with log-transformed cumulative exposure (log-log model). The BaP and BSM cumulative exposure metrics were highly correlated (r = 0.94). The increase in model precision using BaP over BSM was 14% for bladder cancer and 5% for lung cancer; no difference was observed for AMI. The log-linear BaP model provided the best fit for bladder cancer. The log-log dose-response models, where risk of disease plateaus at high exposure levels, were the best-fitting models for lung cancer and AMI. BaP and BSM were both strongly associated with bladder and lung cancer and modestly associated with AMI. Similar conclusions regarding the associations could be made regardless of the exposure metric.

Case Report: Linezolid Optic Neuropathy and Proposed Evidenced-based Screening Recommendation.

PubMed

Dempsey, Sean P; Sickman, Amy; Slagle, William Scott

2018-05-01

This case illustrates a novel screening protocol for linezolid-induced toxic optic neuropathy. To present a case report and analysis of linezolid-induced optic neuropathies in adult patients to develop screening recommendations. A case report of optic neuropathy from extended use of linezolid illustrates its potential effects on vision. We conduct a retrospective analysis of 39 reported cases to derive a recommended screening protocol for linezolid-induced toxic optic neuropathy in adult patients. Of 39 reported adult cases, 32 presented with optic neuropathy within 90 to 365 days of treatment. Within this subset, the duration of linezolid dosage to first symptoms is 235 ± 71 days. Seven outliers either experienced optic neuropathy within the first 28 days or between 600 and 1125 days. Of the 33 cases that quantified visual recovery, 30 reported final binocular visual acuity equivalent to 20/40 or better when the medication was discontinued from 0 to 268 days after symptom onset. Recovery potential was reported over a period of 2 weeks to approximately 6 months after cessation. To evaluate the effect of cumulative dose, the data were separated into patients taking 600 mg twice daily and those at 600 mg once daily. At the higher dosage, a mean of 180 ± 96 days with a mean cumulative dosage of 216 ± 115 g was noted at first symptom, whereas at lower dosage, a mean of 201 ± 102 days was noted with a mean cumulative dose of 138 ± 69 g. We recommend screening adult patients within 1 month after initiating linezolid, followed by a subsequent evaluation every 30 to 60 days beginning 3 months from initiation. Substantial visual recovery is reported when linezolid is discontinued. Toxicity appears to be correlated to duration of treatment, rather than cumulative dose.

Impaired ambulation and steroid therapy impact negatively on bone health in multiple sclerosis.

PubMed

Tyblova, M; Kalincik, T; Zikan, V; Havrdova, E

2015-04-01

The prevalence of osteopenia and osteoporosis is higher amongst patients with multiple sclerosis in comparison with the general population. In addition to the general determinants of bone health, two factors may contribute to reduced bone mineral density in multiple sclerosis: physical disability and corticosteroid therapy. The aim of this study was to examine the effect of physical disability and steroid exposure on bone health in weight-bearing bones and spine and on the incidence of low-trauma fractures in multiple sclerosis. In this retrospective analysis of prospectively collected data, associations between bone mineral density (at the femoral neck, total femur and the lumbar spine) and its change with disability or cumulative steroid dose were evaluated with random-effect models adjusted for demographic and clinical determinants of bone health. The incidence of low-trauma fractures during the study follow-up was evaluated with Andersen-Gill models. Overall, 474 and 438 patients were included in cross-sectional and longitudinal analyses (follow-up 2347 patient-years), respectively. The effect of severely impaired gait was more apparent in weight-bearing bones (P ≤ 10(-15) ) than in spine (P = 0.007). The effect of cumulative steroid dose was relatively less pronounced but diffuse (P ≤ 10(-4) ). Risk of low-trauma fractures was associated with disability (P = 0.02) but not with cumulative steroid exposure and was greater amongst patients with severely impaired gait (annual risk 3.5% vs. 3.0%). Synergistic effects were found only between cumulative steroid dose in patients ambulatory without support (P = 0.02). Bone health and the incidence of low-trauma fractures in multiple sclerosis are more related to impaired gait than to extended corticosteroid therapy. © 2014 The Author(s) European Journal of Neurology © 2014 EAN.

Induction prednisone dosing for childhood nephrotic syndrome: how low should we go?

PubMed

Sibley, Matthew; Roshan, Abishek; Alshami, Alanoud; Catapang, Marisa; Jöbsis, Jasper J; Kwok, Trevor; Polderman, Nonnie; Sibley, Jennifer; Matsell, Douglas G; Mammen, Cherry

2018-05-22

Historically, children with nephrotic syndrome (NS) across British Columbia (BC), Canada have been cared for without formal standardization of induction prednisone dosing. We hypothesized that local historical practice variation in induction dosing was wide and that children treated with lower doses had worse relapsing outcomes. This retrospective cohort study included 92 NS patients from BC Children's Hospital (1990-2010). We excluded secondary causes of NS, age < 1 year at diagnosis, steroid resistance, and incomplete induction due to early relapse. We explored cumulative induction dose and defined dosing quartiles. Relapsing outcomes above and below each quartile threshold were compared including total relapses in 2 years, time to first relapse, and proportions developing frequently relapsing NS (FRNS) or starting a steroid-sparing agent (SSA). Cumulative prednisone was widely distributed with approximated median, 1st, and 3rd quartile doses of 2500, 2000, and 3000 mg/m 2 respectively. Doses ≤ 2000 mg/m 2 showed significantly higher relapses (4.2 vs 2.7), shorter time to first relapse (61 vs 175 days), and higher SSA use (36 vs 14%) compared to higher doses. Doses ≤ 2500 mg/m 2 also showed significantly more relapses (3.9 vs 2.2), quicker first relapse (79 vs 208 days), and higher FRNS (37 vs 17%) and SSA use (28 vs 11%). Relapsing outcomes lacked statistical difference in ≤ 3000 vs > 3000 mg/m 2 doses. Results strongly justify our development of a standardized, province-wide NS clinical pathway to reduce practice variation and minimize under-treatment. The lowest induction prednisone dosing threshold to minimize future relapsing risks is likely between 2000 and 2500 mg/m 2 . Further prospective studies are warranted.

Longitudinal trends in serum ferritin levels and associated factors in a national incident hemodialysis cohort.

PubMed

Kim, Taehee; Rhee, Connie M; Streja, Elani; Obi, Yoshitsugu; Brunelli, Steven M; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar

2017-02-01

The rise in serum ferritin levels among US maintenance hemodialysis patients has been attributed to higher intravenous iron administration and other changes in practice. We examined ferritin trends over time in hemodialysis patients and whether iron utilization patterns and other factors [erythropoietin-stimulating agent (ESA) prescribing patterns, inflammatory markers] were associated with ferritin trajectory. In a 5-year (January 2007–December 2011) cohort of 81 864 incident US hemodialysis patients, we examined changes in ferritin averaged over 3-month intervals using linear mixed effects models adjusted for intravenous iron dose, malnutrition and inflammatory markers. We then examined ferritin trends across strata of baseline ferritin level, dialysis initiation year, cumulative iron and ESA use in the first dialysis year and baseline hemoglobin level. In models adjusted for iron dose, malnutrition and inflammation, mean ferritin levels increased over time in the overall cohort and across the three lower baseline ferritin strata. Among patients initiating dialysis in 2007, mean ferritin levels increased sharply in the first versus second year of dialysis and again abruptly increased in the fifth year independent of iron dose, malnutrition and inflammatory markers; similar trends were observed among patients who initiated dialysis in 2008 and 2009. In analyses stratified by cumulative iron use, mean ferritin increased among groups receiving iron, but decreased in the no iron group. In analyses stratified by cumulative ESA dose and baseline hemoglobin, mean ferritin increased over time. While ferritin trends correlated with patterns of iron use, increases in ferritin over time persisted independent of intravenous iron and ESA exposure, malnutrition and inflammation.

Combined Modality Therapy Including Intraoperative Electron Irradiation for Locally Recurrent Colorectal Cancer

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

Haddock, Michael G., E-mail: haddock.michael@mayo.ed; Miller, Robert C.; Nelson, Heidi

2011-01-01

Purpose: To evaluate survival, relapse patterns, and prognostic factors in patients with colorectal cancer relapse treated with curative-intent therapy, including intraoperative electron radiation therapy (IOERT). Methods and Materials: From April 1981 through January 2008, 607 patients with recurrent colorectal cancer received IOERT as a component of treatment. IOERT was preceded or followed by external radiation (median dose, 45.5 Gy) in 583 patients (96%). Resection was classified as R0 in 227 (37%), R1 in 224 (37%), and R2 in 156 (26%). The median IOERT dose was 15 Gy (range, 7.5-30 Gy). Results: Median overall survival was 36 months. Five- and 10-yearmore » survival rates were 30% and 16%, respectively. Survival estimates at 5 years were 46%, 27%, and 16% for R0, R1, and R2 resection, respectively. Multivariate analysis revealed that R0 resection, no prior chemotherapy, and more recent treatment (in the second half of the series) were associated with improved survival. The 3-year cumulative incidence of central, local, and distant relapse was 12%, 23%, and 49%, respectively. Central and local relapse were more common in previously irradiated patients and in those with subtotal resection. Toxicity Grade 3 or higher partially attributable to IOERT was observed in 66 patients (11%). Neuropathy was observed in 94 patients (15%) and was more common with IOERT doses exceeding 12.5 Gy. Conclusions: Long-term survival and disease control was achievable in patients with locally recurrent colorectal cancer. Continued evaluation of curative-intent, combined-modality therapy that includes IOERT is warranted in this high-risk population.« less

Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6–11 years-old than cumulative high doses of inhaled terbutaline

PubMed Central

Kaae, Rikke; Agertoft, Lone; Pedersen, Sören; Nordvall, S Lennart; Pedroletti, Christophe; Bengtsson, Thomas; Johannes-Hellberg, Ingegerd; Rosenborg, Johan

2004-01-01

Objectives To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. Methods Twenty boys and girls (6–11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxis®) 4.5 µg (F4.5) or terbutaline (Bricanyl®) 500 µg (T500) were inhaled cumulatively via a dry powder inhaler (Turbuhaler®) over 1 h (three patients) or 2.5 h (17 patients) and compared to a day of no treatment, in a randomised, double-blind (active treatments only), crossover trial. Blood pressure (BP), ECG, plasma potassium, glucose, lactate, and adverse events were monitored up to 10 h to assess tolerability and relative systemic dose potency. Results Formoterol and terbutaline had significant β2-adrenergic effects on most outcomes. Apart from the effect on systolic BP, QRS duration and PR interval, the systemic effects were significantly more pronounced with terbutaline than with formoterol. Thus, mean minimum plasma potassium, was suppressed from 3.56 (95% confidence interval, CI: 3.48–3.65) mmol l−1 on the day of no treatment to 2.98 (CI: 2.90–3.08) after 10 × F4.5 and 2.70 (CI: 2.61–2.78) mmol l−1 after 10 × T500, and maximum Q-Tc (heart rate corrected Q-T interval [Bazett's formula]) was prolonged from 429 (CI: 422–435) ms on the day of no treatment, to 455 (CI: 448–462) ms after 10 × F4.5 and 470 (CI: 463–476) ms after 10 × T500. Estimates of relative dose potency indicated that F4.5 µg had the same systemic activity as the clinically less effective dose of 250 µg terbutaline. The duration of systemic effects differed marginally between treatments. Spontaneously reported adverse events (most frequently tremor) were fewer with formoterol (78% of the children) than with terbutaline (95%). A serious adverse event occurred after inhalation of 45 µg formoterol over the 1 h dosing time, that prompted the extension of dosing time to 2.5 h. Conclusions Multiple inhalations over 2.5 h of formoterol (4.5 µg) via Turbuhaler® are at least as safe as and associated with less systemic effects than multiple inhalations of the clinically equipotent dose of terbutaline (500 µg) in children with asthma. PMID:15373934

Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6-11 years-old than cumulative high doses of inhaled terbutaline.

PubMed

Kaae, Rikke; Agertoft, Lone; Pedersen, Sören; Nordvall, S Lennart; Pedroletti, Christophe; Bengtsson, Thomas; Johannes-Hellberg, Ingegerd; Rosenborg, Johan

2004-10-01

To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. Twenty boys and girls (6-11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxis) 4.5 microg (F4.5) or terbutaline (Bricanyl) 500 microg (T500) were inhaled cumulatively via a dry powder inhaler (Turbuhaler) over 1 h (three patients) or 2.5 h (17 patients) and compared to a day of no treatment, in a randomised, double-blind (active treatments only), crossover trial. Blood pressure (BP), ECG, plasma potassium, glucose, lactate, and adverse events were monitored up to 10 h to assess tolerability and relative systemic dose potency. Formoterol and terbutaline had significant beta2-adrenergic effects on most outcomes. Apart from the effect on systolic BP, QRS duration and PR interval, the systemic effects were significantly more pronounced with terbutaline than with formoterol. Thus, mean minimum plasma potassium, was suppressed from 3.56 (95% confidence interval, CI: 3.48-3.65) mmol l(-1) on the day of no treatment to 2.98 (CI: 2.90-3.08) after 10 x F4.5 and 2.70 (CI: 2.61-2.78) mmol l(-1) after 10 x T500, and maximum Q-Tc (heart rate corrected Q-T interval [Bazett's formula]) was prolonged from 429 (CI: 422-435) ms on the day of no treatment, to 455 (CI: 448-462) ms after 10 x F4.5 and 470 (CI: 463-476) ms after 10 x T500. Estimates of relative dose potency indicated that F4.5 microg had the same systemic activity as the clinically less effective dose of 250 microg terbutaline. The duration of systemic effects differed marginally between treatments. Spontaneously reported adverse events (most frequently tremor) were fewer with formoterol (78% of the children) than with terbutaline (95%). A serious adverse event occurred after inhalation of 45 microg formoterol over the 1 h dosing time, that prompted the extension of dosing time to 2.5 h. Multiple inhalations over 2.5 h of formoterol (4.5 microg) via Turbuhaler) are at least as safe as and associated with less systemic effects than multiple inhalations of the clinically equipotent dose of terbutaline (500 microg) in children with asthma. Copyright 2004 Blackwell Publishing Ltd

Evaluation of surface and shallow depth dose reductions using a Superflab bolus during conventional and advanced external beam radiotherapy.

PubMed

Yoon, Jihyung; Xie, Yibo; Zhang, Rui

2018-03-01

The purpose of this study was to evaluate a methodology to reduce scatter and leakage radiations to patients' surface and shallow depths during conventional and advanced external beam radiotherapy. Superflab boluses of different thicknesses were placed on top of a stack of solid water phantoms, and the bolus effect on surface and shallow depth doses for both open and intensity-modulated radiotherapy (IMRT) beams was evaluated using thermoluminescent dosimeters and ion chamber measurements. Contralateral breast dose reduction caused by the bolus was evaluated by delivering clinical postmastectomy radiotherapy (PMRT) plans to an anthropomorphic phantom. For the solid water phantom measurements, surface dose reduction caused by the Superflab bolus was achieved only in out-of-field area and on the incident side of the beam, and the dose reduction increased with bolus thickness. The dose reduction caused by the bolus was more significant at closer distances from the beam. Most of the dose reductions occurred in the first 2-cm depth and stopped at 4-cm depth. For clinical PMRT treatment plans, surface dose reductions using a 1-cm Superflab bolus were up to 31% and 62% for volumetric-modulated arc therapy and 4-field IMRT, respectively, but there was no dose reduction for Tomotherapy. A Superflab bolus can be used to reduce surface and shallow depth doses during external beam radiotherapy when it is placed out of the beam and on the incident side of the beam. Although we only validated this dose reduction strategy for PMRT treatments, it is applicable to any external beam radiotherapy and can potentially reduce patients' risk of developing radiation-induced side effects. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Impact of Chronic Glucocorticoid Treatment on Cardiovascular Risk Profile in Patients with Systemic Lupus Erythematosus.

PubMed

Moya, Fernando Briceño; Pineda Galindo, Luis Francisco; García de la Peña, Maximiliano

2016-01-01

Systemic lupus erythematosus is highly associated with premature atherosclerosis and cardiovascular events. The origin of this subclinical atherosclerosis has been attributed mainly to the inflammatory nature of the disease. To assess the effect of long-term use of glucocorticoids on cardiovascular risk in patients with systemic lupus erythematosus. We conducted a registry-based retrospective cohort study. We determined 2 periods: (1) Time 0, that is, time of diagnosis and (2) time 1, that is, when the study was finalized. At both times, the cardiovascular risk was evaluated using the Framingham scale and their scores were compared. Afterward, the change magnitude between the 2 times was evaluated and associated with the cumulative glucocorticoids dose. One hundred one patients were included. The mean ± SD age was 26.5 ± 5 years. Length of disease evolution was of 7.8 ± 4.9 years. There was an 8-point increase in the Framingham score, from -8.1 ± 4 to 0.8 ± 7; P < 0.0001. The correlation between the magnitude of the increase in Framingham score and their corresponding cumulative dose showed a coefficient of 0.88; P < 0.001. The glucocorticoids are a primary factor that influences cardiovascular risk. There is a directly proportional relationship between the cumulative glucocorticoid dose and the increase in cardiovascular risk.

Enteral Docosahexaenoic Acid Reduces Analgesic Administration in Neonates Undergoing Cardiovascular Surgery.

PubMed

Bernabe-Garcia, Mariela; López-Alarcon, Mardia; Salgado-Sosa, Alfredo; Villegas-Silva, Raul; Maldonado-Hernandez, Jorge; Rodríguez-Cruz, Maricela; Rivas-Ruiz, Rodolfo; Chavez-Sanchez, Luis; Blanco-Favela, Francisco A; Mancilla-Ramirez, Javier; Gordillo-Alvarez, Virginia; Madrigal-Muñiz, Olivia

2016-01-01

Neonates undergoing surgery require analgesic medication to ameliorate acute pain. These medications produce negative side effects. Docosahexaenoic acid (DHA) has an antinociceptive effect in animals, but this has not been evaluated in human neonates. We evaluated the DHA effect on cumulative dose and duration of analgesics administered to neonates undergoing cardiovascular surgery. A secondary analysis was performed with data from a clinical trial, in which enteral DHA was administered perioperatively compared with sunflower oil (SO). Present study assessed the antinociceptive effect of DHA by measuring the cumulative dose and duration of analgesics administered during postoperative stay in a neonatal intensive care unit. Multivariate linear regression models were performed. Seventeen neonates received DHA and 18 received SO in the control group. Compared with the control group, the DHA group received lower cumulative dose (14.6 ± 2.2 vs. 25.2 ± 4.8 μg/kg, p = 0.029) and shorter duration of buprenorphine (2 days (1-8) vs. 4.5 days (1-12); p = 0.053). After adjusting for confounders, the DHA group received significantly lesser buprenorphine (β = -27 μg/kg, p = 0.028; R2 model = 0.90) for shorter duration (β = -9 days, p = 0.003; R2 model = 0.94). No differences in fentanyl or ketorolac were detected. Buprenorphine administration was reduced in neonates who received DHA, suggesting that DHA likely has analgesic effects. © 2016 S. Karger AG, Basel.

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

EPA Science Inventory

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

Patient radiation doses in interventional cardiology in the U.S.: Advisory data sets and possible initial values for U.S. reference levels

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

Miller, Donald L.; Hilohi, C. Michael; Spelic, David C.

2012-10-15

Purpose: To determine patient radiation doses from interventional cardiology procedures in the U.S and to suggest possible initial values for U.S. benchmarks for patient radiation dose from selected interventional cardiology procedures [fluoroscopically guided diagnostic cardiac catheterization and percutaneous coronary intervention (PCI)]. Methods: Patient radiation dose metrics were derived from analysis of data from the 2008 to 2009 Nationwide Evaluation of X-ray Trends (NEXT) survey of cardiac catheterization. This analysis used deidentified data and did not require review by an IRB. Data from 171 facilities in 30 states were analyzed. The distributions (percentiles) of radiation dose metrics were determined for diagnosticmore » cardiac catheterizations, PCI, and combined diagnostic and PCI procedures. Confidence intervals for these dose distributions were determined using bootstrap resampling. Results: Percentile distributions (advisory data sets) and possible preliminary U.S. reference levels (based on the 75th percentile of the dose distributions) are provided for cumulative air kerma at the reference point (K{sub a,r}), cumulative air kerma-area product (P{sub KA}), fluoroscopy time, and number of cine runs. Dose distributions are sufficiently detailed to permit dose audits as described in National Council on Radiation Protection and Measurements Report No. 168. Fluoroscopy times are consistent with those observed in European studies, but P{sub KA} is higher in the U.S. Conclusions: Sufficient data exist to suggest possible initial benchmarks for patient radiation dose for certain interventional cardiology procedures in the U.S. Our data suggest that patient radiation dose in these procedures is not optimized in U.S. practice.« less

Evidence for dose-additive effects of pyrethroids on motor activity in rats.

PubMed

Wolansky, Marcelo J; Gennings, Chris; DeVito, Michael J; Crofton, Kevin M

2009-10-01

Pyrethroids are neurotoxic insecticides used in a variety of indoor and outdoor applications. Previous research characterized the acute dose-effect functions for 11 pyrethroids administered orally in corn oil (1 mL/kg) based on assessment of motor activity. We used a mixture of these 11 pyrethroids and the same testing paradigm used in single-compound assays to test the hypothesis that cumulative neurotoxic effects of pyrethroid mixtures can be predicted using the default dose-addition theory. Mixing ratios of the 11 pyrethroids in the tested mixture were based on the ED30 (effective dose that produces a 30% decrease in response) of the individual chemical (i.e., the mixture comprised equipotent amounts of each pyrethroid). The highest concentration of each individual chemical in the mixture was less than the threshold for inducing behavioral effects. Adult male rats received acute oral exposure to corn oil (control) or dilutions of the stock mixture solution. The mixture of 11 pyrethroids was administered either simultaneously (2 hr before testing) or after a sequence based on times of peak effect for the individual chemicals (4, 2, and 1 hr before testing). A threshold additivity model was fit to the single-chemical data to predict the theoretical dose-effect relationship for the mixture under the assumption of dose additivity. When subthreshold doses of individual chemicals were combined in the mixtures, we found significant dose-related decreases in motor activity. Further, we found no departure from the predicted dose-additive curve regardless of the mixture dosing protocol used. In this article we present the first in vivo evidence on pyrethroid cumulative effects supporting the default assumption of dose addition.

Application of computational models to estimate organ radiation dose in rainbow trout from uptake of molybdenum-99 with comparison to iodine-131.

PubMed

Martinez, N E; Johnson, T E; Pinder, J E

2016-01-01

This study compares three anatomical phantoms for rainbow trout (Oncorhynchus mykiss) for the purpose of estimating organ radiation dose and dose rates from molybdenum-99 ((99)Mo) uptake in the liver and GI tract. Model comparison and refinement is important to the process of determining accurate doses and dose rates to the whole body and the various organs. Accurate and consistent dosimetry is crucial to the determination of appropriate dose-effect relationships for use in environmental risk assessment. The computational phantoms considered are (1) a geometrically defined model employing anatomically relevant organ size and location, (2) voxel reconstruction of internal anatomy obtained from CT imaging, and (3) a new model utilizing NURBS surfaces to refine the model in (2). Dose Conversion Factors (DCFs) for whole body as well as selected organs of O. mykiss were computed using Monte Carlo modeling and combined with empirical models for predicting activity concentration to estimate dose rates and ultimately determine cumulative radiation dose (μGy) to selected organs after several half-lives of (99)Mo. The computational models provided similar results, especially for organs that were both the source and target of radiation (less than 30% difference between all models). Values in the empirical model as well as the 14 day cumulative organ doses determined from (99)Mo uptake are compared to similar models developed previously for (131)I. Finally, consideration is given to treating the GI tract as a solid organ compared to partitioning it into gut contents and GI wall, which resulted in an order of magnitude difference in estimated dose for most organs. Copyright © 2015 Elsevier Ltd. All rights reserved.

An influential factor for external radiation dose estimation for residents after the Fukushima Daiichi Nuclear Power Plant accident-time spent outdoors for residents in Iitate Village.

PubMed

Ishikawa, Tetsuo; Yasumura, Seiji; Ohtsuru, Akira; Sakai, Akira; Akahane, Keiichi; Yonai, Shunsuke; Sakata, Ritsu; Ozasa, Kotaro; Hayashi, Masayuki; Ohira, Tetsuya; Kamiya, Kenji; Abe, Masafumi

2016-06-01

Many studies have been conducted on radiation doses to residents after the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident. Time spent outdoors is an influential factor for external dose estimation. Since little information was available on actual time spent outdoors for residents, different values of average time spent outdoors per day have been used in dose estimation studies on the FDNPP accident. The most conservative value of 24 h was sometimes used, while 2.4 h was adopted for indoor workers in the UNSCEAR 2013 report. Fukushima Medical University has been estimating individual external doses received by residents as a part of the Fukushima Health Management Survey by collecting information on the records of moves and activities (the Basic Survey) after the accident from each resident. In the present study, these records were analyzed to estimate an average time spent outdoors per day. As an example, in Iitate Village, its arithmetic mean was 2.08 h (95% CI: 1.64-2.51) for a total of 170 persons selected from respondents to the Basic Survey. This is a much smaller value than commonly assumed. When 2.08 h is used for the external dose estimation, the dose is about 25% (23-26% when using the above 95% CI) less compared with the dose estimated for the commonly used value of 8 h.

Radiation exposure due to local fallout from Soviet atmospheric nuclear weapons testing in Kazakhstan: solid cancer mortality in the Semipalatinsk historical cohort, 1960-1999.

PubMed

Bauer, Susanne; Gusev, Boris I; Pivina, Ludmila M; Apsalikov, Kazbek N; Grosche, Bernd

2005-10-01

Little information is available on the health effects of exposures to fallout from Soviet nuclear weapons testing and on the combined external and internal environmental exposures that have resulted from these tests. This paper reports the first analysis of the Semipalatinsk historical cohort exposed in the vicinity of the Semipalatinsk nuclear test site, Kazakhstan. The cohort study, which includes 19,545 inhabitants of exposed and comparison villages of the Semipalatinsk region, was set up in the 1960s and comprises 582,750 person-years of follow-up between 1960 and 1999. Cumulative effective radiation dose estimates in this cohort range from 20 mSv to approximately 4 Sv. Rates of mortality and cancer mortality in the exposed group substantially exceeded those of the comparison group. Dose-response analyses within the exposed group confirmed a significant trend with dose for all solid cancers (P < 0.0001) and for digestive and respiratory cancers (P = 0.0255 and P < 0.0001), whereas no consistent dose-response trend was found for all causes of death (P = 0.4296). Regarding specific cancer sites, a significant trend with dose was observed for lung cancer (P = 0.0001), stomach cancer (P = 0.0050), and female breast cancer (P = 0.0040) as well as for esophagus cancer in women (P = 0.0030). The excess relative risk per sievert for all solid cancers combined was 1.77 (1.35; 2.27) based on the total cohort data, yet a selection bias regarding the comparison group could not be entirely ruled out. The excess relative risk per sievert based on the cohort's exposed group was 0.81 (0.46; 1.33) for all solid cancers combined and thus still exceeds current risk estimates from the Life Span Study. Future epidemiological assessments based on this cohort will benefit from extension of follow-up and ongoing validation of dosimetric data.

Effect of Gold Nanoparticles on Prostate Dose Distribution under Ir-192 Internal and 18 MV External Radiotherapy Procedures Using Gel Dosimetry and Monte Carlo Method.

PubMed

Khosravi, H; Hashemi, B; Mahdavi, S R; Hejazi, P

2015-03-01

Gel polymers are considered as new dosimeters for determining radiotherapy dose distribution in three dimensions. The ability of a new formulation of MAGIC-f polymer gel was assessed by experimental measurement and Monte Carlo (MC) method for studying the effect of gold nanoparticles (GNPs) in prostate dose distributions under the internal Ir-192 and external 18MV radiotherapy practices. A Plexiglas phantom was made representing human pelvis. The GNP shaving 15 nm in diameter and 0.1 mM concentration were synthesized using chemical reduction method. Then, a new formulation of MAGIC-f gel was synthesized. The fabricated gel was poured in the tubes located at the prostate (with and without the GNPs) and bladder locations of the phantom. The phantom was irradiated to an Ir-192 source and 18 MV beam of a Varian linac separately based on common radiotherapy procedures used for prostate cancer. After 24 hours, the irradiated gels were read using a Siemens 1.5 Tesla MRI scanner. The absolute doses at the reference points and isodose curves resulted from the experimental measurement of the gels and MC simulations following the internal and external radiotherapy practices were compared. The mean absorbed doses measured with the gel in the presence of the GNPs in prostate were 15% and 8 % higher than the corresponding values without the GNPs under the internal and external radiation therapies, respectively. MC simulations also indicated a dose increase of 14 % and 7 % due to presence of the GNPs, for the same experimental internal and external radiotherapy practices, respectively. There was a good agreement between the dose enhancement factors (DEFs) estimated with MC simulations and experiment gel measurements due to the GNPs. The results indicated that the polymer gel dosimetry method as developed and used in this study, can be recommended as a reliable method for investigating the DEF of GNPs in internal and external radiotherapy practices.

Radiological dose in Muria peninsula from SB-LOCA event

NASA Astrophysics Data System (ADS)

Sunarko; Suud, Zaki

2017-01-01

Dose assessment for accident condition is performed for Muria Peninsula region using source-term from Three-Mile Island unit 2 SB-LOCA accident. Xe-133, Kr-88, 1-131 and Cs-137 isotopes are considered in the calculation. The effluent is assumed to be released from a 50 m stack. Lagrangian particle dispersion method (LPDM) employing non-Gaussian dispersion coefficient in 3-dimensional mass-consistent wind-field is employed to obtain periodic surface-level concentration which is then time-integrated to obtain spatial distribution of ground-level dose. In 1-hour simulation, segmented plumes with 60 seconds duration with a total of 18.000 particles involved. Simulations using 6-hour worst-case meteorological data from Muria peninsula results in a peak external dose of around 1.668 mSv for low scenario and 6.892 mSv for high scenario in dry condition. In wet condition with 5 mm/hour and 10 mm/hour rain for the whole duration of the simulation provides only minor effect to dose. The peak external dose is below the regulatory limit of 50 mSv for effective skin dose from external gamma exposure.

The dose of hydroxyethyl starch 6% 130/0.4 for fluid therapy and the incidence of acute kidney injury after cardiac surgery: A retrospective matched study

PubMed Central

Nkoy Ena, Lompoli; Van Dyck, Michel; Matta, Amine; Kahn, David; Thiry, Dominique; Grégoire, André; Watremez, Christine

2017-01-01

The safety of hydroxyethyl starches (HES) is still under debate. No studies have compared different dosing regimens of HES in cardiac surgery. We analyzed whether the incidence of Acute Kidney Injury (AKI) differed taking into account a weight-adjusted cumulative dose of HES 6% 130/0.4 for perioperative fluid therapy. This retrospective cohort study included all adult patients undergoing elective or emergency cardiac surgery with or without cardiopulmonary bypass. Exclusion criteria were patients on renal replacement therapy (RRT), cardiac trauma surgery, heart transplantation, patients with ventricular assist devices, subjects who required a surgical revision for bleeding and those whose medical records were incomplete. Primary endpoint was AKI following the creatinine based RIFLE classification. Secondary endpoints were 30-day mortality and RRT. Patients were divided into 2 groups whether they had received a cumulative HES dose of < 30 mL/kg (Low HES) or ≥ 30 mL/kg (High HES) during the intra- and postoperative period. A total of 1501 patients were analyzed with 983 patients in the Low HES and 518 subjects in the High HES group. 185 (18.8%) patients in the Low HES and 119 (23.0%) patients in the High HES group developed AKI (P = 0.06). In multivariable regression analysis the dose of HES administered per weight was not associated with AKI. After case-control matching 217 patients were analyzed in each group. AKI occurred in 39 (18.0%) patients in the Low HES and 50 (23.0%) patients in the High HES group (P = 0.19). In conditional regression analysis performed on the matched groups a lower weight-adjusted dose of HES was significantly associated with a reduced incidence of AKI [(Odds Ratio (95% CI) = 0.825 (0.727–0.936); P = 0.003]. In the absence of any safety study the cumulative dose of modern HES in cardiac surgery should be kept less than 30 mL/kg. PMID:29045467

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

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

Gao, Z; Li, M; Wong, J

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

Comprehensive data on ionising radiation from Fukushima Daiichi nuclear power plant in the town of Miharu, Fukushima Prefecture: The Misho Project.

PubMed

Koike, T; Suzuki, Y; Genyu, S; Kobayashi, I; Komori, H; Otsu, H; Sakuma, H; Sakuma, K; Sarausad, E M; Shimada, K; Shinozuka, T; Tamura, H; Tsukada, K; Ukai, M; Yamamoto, T O

2014-09-01

Data related to radioactivity released from the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident on 15 March 2011 gathered by residents of Miharu, Fukushima Prefecture, and by Tohoku University are presented. These data sets consist of (1) the earliest radiation monitoring by a Geiger counter in the town, (2) ratios of radioactivity between (132)Te and (137)Cs for a wide area between Fukushima and Tokyo, (3) radiation measurement of soil samples collected from 18 school grounds, and (4) external radiation exposure of 1400 students using OSL badges. By combining and analysing these various data sets, a curve for the cumulative total external exposure as a function of time, with 16 : 00 h on 15 March 2011 being time zero, is obtained. The average cumulative external dosage is estimated to be 10 mSv (σ = 4.2 mSv) over 10 years. In addition, the initiative that the residents of Miharu took in response to the FDNPP accident, which became known as The Misho Project (MP), is documented; in particular, the time at which the municipality instructed the immediate ingestion of iodine tablets by those under the age of 40, 13 : 00 h on 15 March 2011, is assessed.

Changes in post-traumatic symptom pattern during and after exposure to extreme war stress: an uncontrolled, preliminary study supporting the dose-response model.

PubMed

Ben-Ezra, Menachem; Palgi, Yuval; Shrira, Amit; Sternberg, Dina; Essar, Nir

2010-01-01

Exposure to prolonged war stress is understudied. While there is debate regarding the empirical data of the dose-response model for posttraumatic stress disorder (PTSD), little is known about how weekly changes in external stress influences the level of PTSD symptoms. The purpose of this study was to measure the relation between objective external stress and PTSD symptoms across time, and thus, gain a deeper understating of the dose-response model. The study hypothesis postulates that the more severe the external stressor, the more severe the exhibition of traumatic symptoms. Thirteen special army administrative staff (SAAS) members from the Rambam Medical Center in Haifa attended seven intervention meetings during the war. These personnel answered a battery of questionnaires regarding demographics and PTSD symptoms during each session. A non-parametric test was used in order to measure the changes in PTSD symptoms between sessions. Pearson correlations were used in order to study the relationship between the magnitude of external stressors and the severity of PTSD symptoms. The results suggested that there was a significant relationship between the magnitude of external stressors and the severity of PTSD symptoms. These results are in line with the dose-response model. The results suggest that a pattern of decline in PTSD symptoms confirm the dose-response model for PTSD.

The role of cumulative physical work load in symptomatic knee osteoarthritis – a case-control study in Germany

PubMed Central

Seidler, Andreas; Bolm-Audorff, Ulrich; Abolmaali, Nasreddin; Elsner, Gine

2008-01-01

Objectives To examine the dose-response relationship between cumulative exposure to kneeling and squatting as well as to lifting and carrying of loads and symptomatic knee osteoarthritis (OA) in a population-based case-control study. Methods In five orthopedic clinics and five practices we recruited 295 male patients aged 25 to 70 with radiographically confirmed knee osteoarthritis associated with chronic complaints. A total of 327 male control subjects were recruited. Data were gathered in a structured personal interview. To calculate cumulative exposure, the self-reported duration of kneeling and squatting as well as the duration of lifting and carrying of loads were summed up over the entire working life. Results The results of our study support a dose-response relationship between kneeling/squatting and symptomatic knee osteoarthritis. For a cumulative exposure to kneeling and squatting > 10.800 hours, the risk of having radiographically confirmed knee osteoarthritis as measured by the odds ratio (adjusted for age, region, weight, jogging/athletics, and lifting or carrying of loads) is 2.4 (95% CI 1.1–5.0) compared to unexposed subjects. Lifting and carrying of loads is significantly associated with knee osteoarthritis independent of kneeling or similar activities. Conclusion As the knee osteoarthritis risk is strongly elevated in occupations that involve both kneeling/squatting and heavy lifting/carrying, preventive efforts should particularly focus on these "high-risk occupations". PMID:18625053

2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity in yellow perch (Perca flavescens)

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

Spitsbergen, J.M.; Kleeman, J.M.; Peterson, R.E.

1988-01-01

Growth, mortality and morphologic lesions in juvenile, hatchery-reared yellow perch, Perca flavescens, were studied after treatment with graded single doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 1-125 ..mu..g/kg, intraperitoneally). TCDD doses of 25 and 125 ..mu..g/kg caused 95% mortality by 28 d after treatment, without decreasing body weight. A TCDD dose of 5 ..mu..g/kg resulted in progressive loss of body weight with cumulative mortality of 80% by 80 d posttreatment. Periodic handling stress did not affect the time course of mortality or cumulative percent lethality in TCDD-treated perch. Fin necrosis, petechial cutaneous hemorrhage, and ascites occurred in perch treated with 5 ..mu..g/kg ormore » more of TCDD. Thymic atrophy, decreased hematopoiesis in the head kidney, fibrinous pericarditis, focal myocardial necrosis, submucosal gastric edema, and hyperplasia of the epithelium of gill filaments and lamellae occurred in perch dosed with 25 or 125 ..mu..g/kg. Dose-related splenic lymphoid depletion occurred in perch receiving 5 ..mu..g/kg or more TCDD, and hepatocycte lipidosis occurred in groups treated with doses of 1 ..mu..g/kg or more TCDD. Thus yellow perch are as responsive to the acute toxic effects of TCDD as some of the more sensitive mammalian species, and neither loss of body weight nor histologic lesions in TCDD-treated perch are sufficient to explain mortality.« less

Towards personalized therapy for multiple sclerosis: prediction of individual treatment response.

PubMed

Kalincik, Tomas; Manouchehrinia, Ali; Sobisek, Lukas; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Girard, Marc; Prat, Alexandre; Duquette, Pierre; Grammond, Pierre; Sola, Patrizia; Hupperts, Raymond; Grand'Maison, Francois; Pucci, Eugenio; Boz, Cavit; Alroughani, Raed; Van Pesch, Vincent; Lechner-Scott, Jeannette; Terzi, Murat; Bergamaschi, Roberto; Iuliano, Gerardo; Granella, Franco; Spitaleri, Daniele; Shaygannejad, Vahid; Oreja-Guevara, Celia; Slee, Mark; Ampapa, Radek; Verheul, Freek; McCombe, Pamela; Olascoaga, Javier; Amato, Maria Pia; Vucic, Steve; Hodgkinson, Suzanne; Ramo-Tello, Cristina; Flechter, Shlomo; Cristiano, Edgardo; Rozsa, Csilla; Moore, Fraser; Luis Sanchez-Menoyo, Jose; Laura Saladino, Maria; Barnett, Michael; Hillert, Jan; Butzkueven, Helmut

2017-09-01

Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and (ii) to evaluate accuracy, and internal and external validity of these algorithms. This study evaluated 27 demographic, clinical and paraclinical predictors of individual response to seven disease-modifying therapies in MSBase, a large global cohort study. Treatment response was analysed separately for disability progression, disability regression, relapse frequency, conversion to secondary progressive disease, change in the cumulative disease burden, and the probability of treatment discontinuation. Multivariable survival and generalized linear models were used, together with the principal component analysis to reduce model dimensionality and prevent overparameterization. Accuracy of the individual prediction was tested and its internal validity was evaluated in a separate, non-overlapping cohort. External validity was evaluated in a geographically distinct cohort, the Swedish Multiple Sclerosis Registry. In the training cohort (n = 8513), the most prominent modifiers of treatment response comprised age, disease duration, disease course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pretreatment relapse activity. The probability of disability regression was predominantly associated with pre-baseline disability, therapy and relapse activity. Relapse incidence was associated with pretreatment relapse activity, age and relapsing disease course, with the strength of these associations varying among therapies. Accuracy and internal validity (n = 1196) of the resulting predictive models was high (>80%) for relapse incidence during the first year and for disability outcomes, moderate for relapse incidence in Years 2-4 and for the change in the cumulative disease burden, and low for conversion to secondary progressive disease and treatment discontinuation. External validation showed similar results, demonstrating high external validity for disability and relapse outcomes, moderate external validity for cumulative disease burden and low external validity for conversion to secondary progressive disease and treatment discontinuation. We conclude that demographic, clinical and paraclinical information helps predict individual response to disease-modifying therapies at the time of their commencement. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Meeting The Joint Commission's Dose Incident Identification and External Benchmarking Requirements Using the ACR's Dose Index Registry.

PubMed

Bohl, Michael A; Goswami, Roopa; Strassner, Brett; Stanger, Paula

2016-08-01

The purpose of this investigation was to evaluate the potential of using the ACR's Dose Index Registry(®) to meet The Joint Commission's requirements to identify incidents in which the radiation dose index from diagnostic CT examinations exceeded the protocol's expected dose index range. In total, 10,970 records in the Dose Index Registry were statistically analyzed to establish both an upper and lower expected dose index for each protocol. All 2015 studies to date were then retrospectively reviewed to identify examinations whose total examination dose index exceeded the protocol's defined upper threshold. Each dose incident was then logged and reviewed per the new Joint Commission requirements. Facilities may leverage their participation in the ACR's Dose Index Registry to fully meet The Joint Commission's dose incident identification review and external benchmarking requirements. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Multiple mediators of the relationships among maternal childhood abuse, intimate partner violence, and offspring psychopathology.

PubMed

Miranda, Jenniffer K; de la Osa, Nuria; Granero, Roser; Ezpeleta, Lourdes

2013-09-01

The aim of the study was to examine whether maternal depression, mothers' and fathers' parenting, child physical punishment and negative life events (NLE) mediate the effect of maternal childhood abuse (CA), intimate partner violence (IPV) and cumulative violence (both CA and IPV) on Spanish children's and adolescents' psychopathology. Furthermore, multiple mediator models examine whether IPV mediates the effect of CA on the contextual and family factors mentioned above. Three hundred and eighteen Spanish outpatients aged 7 to 18 and their parents were assessed using a structured interview and other instruments for measuring the study variables. Structural equation models (SEMs) showed multiple pathways explaining psychopathological problems among offspring of mothers who suffered CA, IPV and both of these violent experiences. In particular, mothers' depression mediated the link between maternal CA, IPV, cumulative violence and children's externalizing, and total behavior problems. Child NLE was an important pathway between maternal CA and total behavior problems, as well as between cumulative violence and both externalizing and total problems. IPV contributed to explaining the link between maternal CA and contextual and family factors, such as child physical punishment and NLE, which were in turn, associated with children's behavior problems. Findings show the complex interconnections between different types of violence and their harmful effects on the mental health of women and their offspring, as well as the need to extend our knowledge on this subject.

[Effects of biochar addition into soils in semiarid land on water infiltration under the condition of the same bulk density].

PubMed

Qi, Rui-Peng; Zhang, Lei; Yan, Yong-Hao; Wen, Man; Zheng, Ji-Yong

2014-08-01

Making clear the effects of biochar addition on soil water infiltration process can provide the scientific basis for the evaluation of the influence of biochar application on soil hydrology in semi-arid region. In this paper, through the soil column simulation method in laboratory, the effects of biochar of three sizes (1-2 mm, 0.25-1 mm and ≤ 0.25 mm) at 4 doses (10, 50, 100 and 150 g x kg(-1)) on the cumulative infiltration, the permeability and the stable infiltration rate of two different soils (anthrosol and aeolian sandy soil) were studied. The results showed that the infiltration capacity of the anthrosol was obviously increased compared to the control, however, the one in the aeolian sandy soil was decreased due to the biochar addition. At 100 minutes after infiltration starting, the averaged cumulative infiltration was increased by 25.1% in the anthrosol with comparison to the control. Contrarily, the averaged cumulative infiltration was decreased by 11.1% in the aeolian sandy soil at 15 minutes after infiltration starting. When the dose was the same, biochar with different particle sizes improved the infiltration for the anthrosol, but for the different dose treatments, the particle size of biochar which showed the greatest improvement was different. As for the aeolian sandy soil, the infiltration increased at the dose of 10 g x kg(-1) after the addition of biochar with different particle sizes, while decreased at the higher dose of 50, 100 and 150 g x kg(-1). The cumulative infiltration of the aeolian sandy soil was decreased with the increase in addition amount of biochar with the same particle size, while it was not so for the anthrosol. The determination coefficient fitted by the Philip infiltration model ranged from 0.965 to 0.999, suggesting this model was suitable for the simulation of soil water infiltration process after biochar application. Statistical analysis of main effects showed that the biochar particle size, the biochar addition amount, and the interactive effect had statistically significant effect on the soil permeability and stable infiltration rate in the two soils. In conclusion, the biochar had different effects on the soils with different textures, moreover, there was a positive correlation relationship between the impact and the addition amount.

Data requirements for valuing externalities: The role of existing permitting processes

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

Lee, A.D.; Baechler, M.C.; Callaway, J.M.

1990-08-01

While the assessment of externalities, or residual impacts, will place new demands on regulators, utilities, and developers, existing processes already require certain data and information that may fulfill some of the data needs for externality valuation. This paper examines existing siting, permitting, and other processes and highlights similarities and differences between their data requirements and the data required to value environmental externalities. It specifically considers existing requirements for siting new electricity resources in Oregon and compares them with the information and data needed to value externalities for such resources. This paper also presents several observations about how states can takemore » advantage of data acquired through processes already in place as they move into an era when externalities are considered in utility decision-making. It presents other observations on the similarities and differences between the data requirements under existing processes and those for valuing externalities. This paper also briefly discusses the special case of cumulative impacts. And it presents recommendations on what steps to take in future efforts to value externalities. 35 refs., 2 tabs.« less

Cumulative Effects of In Utero Administration of Mixtures of Reproductive Toxicants that Disrupt Common Target Tissues via Diverse Mechanisms of Toxicity

PubMed Central

Rider, Cynthia V.; Furr, Johnathan R.; Wilson, Vickie S.; Gray, L. Earl

2010-01-01

Although risk assessments are typically conducted on a chemical-by-chemical basis, the 1996 Food Quality Protection Act required the US Environmental Protection Agency to consider cumulative risk of chemicals that act via a common mechanism of toxicity. To this end, we are conducting studies with mixtures of chemicals to elucidate mechanisms of joint action at the systemic level with the end goal of providing a framework for assessing the cumulative effects of reproductive toxicants. Previous mixture studies conducted with antiandrogenic chemicals are reviewed briefly and two new studies are described in detail. In all binary mixture studies, rats were dosed during pregnancy with chemicals, singly or in pairs at dosage levels equivalent to approximately one half of the ED50 for hypospadias or epididymal agenesis. The binary mixtures included: androgen receptor (AR) antagonists (vinclozolin plus procymidone), phthalate esters (DBP plus BBP and DEHP plus DBP), a phthalate ester plus an AR antagonist (DBP plus procymidone), a mixed mechanism androgen signaling disruptor (linuron) plus BBP, and two chemicals which disrupt epididymal differentiation through entirely different toxicity pathways: DBP (AR pathway) plus 2,3,7,8 TCDD (AhR pathway). We also conducted multi-component mixture studies combining several “antiandrogens” together. In the first study, seven chemicals (four pesticides and three phthalates) that elicit antiandrogenic effects at two different sites in the androgen signaling pathway (i.e. AR antagonist or inhibition of androgen synthesis) were combined. In the second study, three additional phthalates were added to make a ten chemical mixture. In both the binary mixture studies and the multi-component mixture studies, chemicals that targeted male reproductive tract development displayed cumulative effects that exceeded predictions based upon a response addition model and most often were in accordance with predictions based upon dose addition models. In summary, our results indicate that compounds that act by disparate mechanisms of toxicity to disrupt the dynamic interactions among the interconnected signaling pathways in differentiating tissues produce cumulative dose-additive effects, regardless of the mechanism or mode of action of the individual mixture component. PMID:20487044

Live Bacterial Physiology Visualized with 5 nm Resolution Using Scanning Transmission Electron Microscopy.

PubMed

Kennedy, Eamonn; Nelson, Edward M; Tanaka, Tetsuya; Damiano, John; Timp, Gregory

2016-02-23

It is now possible to visualize at nanometer resolution the infection of a living biological cell with virus without compromising cell viability using scanning transmission electron microscopy (STEM). To provide contrast while preserving viability, Escherichia coli and P1 bacteriophages were first positively stained with a very low concentration of uranyl acetate in minimal phosphate medium and then imaged with low-dose STEM in a microfluidic liquid flow cell. Under these conditions, it was established that the median lethal dose of electrons required to kill half the tested population was LD50 = 30 e(-)/nm(2), which coincides with the disruption of a wet biological membrane, according to prior reports. Consistent with the lateral resolution and high-contrast signal-to-noise ratio (SNR) inferred from Monte Carlo simulations, images of the E. coli membrane, flagella, and the bacteriophages were acquired with 5 nm resolution, but the cumulative dose exceeded LD50. On the other hand, with a cumulative dose below LD50 (and lower SNR), it was still possible to visualize the infection of E. coli by P1, showing the insertion of viral DNA within 3 s, with 5 nm resolution.

Analytic concepts for assessing risk as applied to human space flight

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

Garrick, B J

Quantitative risk assessment (QRA) principles provide an effective framework for quantifying individual elements of risk, including the risk to astronauts and spacecraft of the radiation environment of space flight. The concept of QRA is based on a structured set of scenarios that could lead to different damage states initiated by either hardware failure, human error, or external events. In the context of a spacecraft risk assessment, radiation may be considered as an external event and analyzed in the same basic way as any other contributor to risk. It is possible to turn up the microscope on any particular contributor tomore » risk and ask more detailed questions than might be necessary to simply assess safety. The methods of QRA allow for as much fine structure in the analysis as is desired. For the purpose of developing a basis for comprehensive risk management and considering the tendency to {open_quotes}fear anything nuclear,{close_quotes} radiation risk is a prime candidate for examination beyond that necessary to answer the basic question of risk. Thus, rather than considering only the customary damage states of fatalities or loss of a spacecraft, it is suggested that the full range of damage be analyzed to quantify radiation risk. Radiation dose levels in the form of a risk curve accomplish such a result. If the risk curve is the complementary cumulative distribution function, then it answers the extended question of what is the likelihood of receiving a specific dose of radiation or greater. Such results can be converted to specific health effects as desired. Knowing the full range of the radiation risk of a space mission and the contributors to that risk provides the information necessary to take risk management actions [operational, design, scheduling of missions around solar particle events (SPE), etc.] that clearly control radiation exposure.« less

Hand and body radiation exposure with the use of mini C-arm fluoroscopy.

PubMed

Tuohy, Christopher J; Weikert, Douglas R; Watson, Jeffry T; Lee, Donald H

2011-04-01

To determine whole body and hand radiation exposure to the hand surgeon wearing a lead apron during routine intraoperative use of the mini C-arm fluoroscope. Four surgeons (3 hand attending surgeons and 1 hand fellow) monitored their radiation exposure for a total of 200 consecutive cases (50 cases per surgeon) requiring mini C-arm fluoroscopy. Each surgeon measured radiation exposure with a badge dosimeter placed on the outside breast pocket of the lead apron (external whole body exposure), a second badge dosimeter under the lead apron (shielded whole body exposure), and a ring dosimeter (hand exposure). Completed records were noted in 198 cases, with an average fluoroscopy time of 133.52 seconds and average cumulative dose of 19,260 rem-cm(2) per case. The total measured radiation exposures for the (1) external whole body exposure dosimeters were 16 mrem (for shallow depth), 7 mrem (for eye depth), and less than 1 mrem (for deep depth); (2) shielded whole body badge dosimeters recorded less than 1 mrem; and (3) ring dosimeters totaled 170 mrem. The total radial exposure for 4 ring dosimeters that had registered a threshold of 30 mrem or more of radiation exposure was 170 mrem at the skin level, for an average of 42.5 mrem per dosimeter ring or 6.3 mrem per case. This study of whole body and hand radiation exposure from the mini C-arm includes the largest number of surgical cases in the published literature. The measured whole body and hand radiation exposure received by the hand surgeon from the mini C-arm represents a minimal risk of radiation, based on the current National Council on Radiation Protection and Management standards of annual dose limits (5,000 mrem per year for whole body and 50,000 mrem per year to the extremities). Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Investigation of practical approaches to evaluating cumulative dose for cone beam computed tomography (CBCT) from standard CT dosimetry measurements: a Monte Carlo study.

PubMed

Abuhaimed, Abdullah; Martin, Colin J; Sankaralingam, Marimuthu; Gentle, David J

2015-07-21

A function called Gx(L) was introduced by the International Commission on Radiation Units and Measurements (ICRU) Report-87 to facilitate measurement of cumulative dose for CT scans within long phantoms as recommended by the American Association of Physicists in Medicine (AAPM) TG-111. The Gx(L) function is equal to the ratio of the cumulative dose at the middle of a CT scan to the volume weighted CTDI (CTDIvol), and was investigated for conventional multi-slice CT scanners operating with a moving table. As the stationary table mode, which is the basis for cone beam CT (CBCT) scans, differs from that used for conventional CT scans, the aim of this study was to investigate the extension of the Gx(L) function to CBCT scans. An On-Board Imager (OBI) system integrated with a TrueBeam linac was simulated with Monte Carlo EGSnrc/BEAMnrc, and the absorbed dose was calculated within PMMA, polyethylene (PE), and water head and body phantoms using EGSnrc/DOSXYZnrc, where the body PE body phantom emulated the ICRU/AAPM phantom. Beams of width 40-500 mm and beam qualities at tube potentials of 80-140 kV were studied. Application of a modified function of beam width (W) termed Gx(W), for which the cumulative dose for CBCT scans f (0) is normalized to the weighted CTDI (CTDIw) for a reference beam of width 40 mm, was investigated as a possible option. However, differences were found in Gx(W) with tube potential, especially for body phantoms, and these were considered to be due to differences in geometry between wide beams used for CBCT scans and those for conventional CT. Therefore, a modified function Gx(W)100 has been proposed, taking the form of values of f (0) at each position in a long phantom, normalized with respect to dose indices f 100(150)x measured with a 100 mm pencil ionization chamber within standard 150 mm PMMA phantoms, using the same scanning parameters, beam widths and positions within the phantom. f 100(150)x averages the dose resulting from a CBCT scan over the 100 mm length. Like the Gx(L) function, the Gx(W)100 function showed only a weak dependency on tube potential at most positions for the phantoms studied. The results were fitted to polynomial equations from which f (0) within the longer PMMA, PE, or water phantoms can be evaluated from measurements of f 100(150)x. Comparisons with other studies, suggest that these functions may be suitable for application to any CT or CBCT scan acquired with stationary table mode.

Predictive factors of head and neck squamous cell carcinoma patient tolerance to high-dose cisplatin in concurrent chemoradiotherapy

PubMed Central

NAKANO, KENJI; SATO, YASUYOSHI; TOSHIYASU, TAKASHI; SATO, YUKIKO; INAGAKI, LINA; TOMOMATSU, JUNICHI; SASAKI, TORU; SHIMBASHI, WATARU; FUKUSHIMA, HIROFUMI; YONEKAWA, HIROYUKI; MITANI, HIROKI; KAWABATA, KAZUYOSHI; TAKAHASHI, SHUNJI

2016-01-01

Although high-dose cisplatin is the standard regimen of concurrent chemoradiotherapy (CCRT) for locally advanced head and neck squamous cell carcinoma (HNSCC), varying levels of patient tolerance towards cisplatin have been reported, and the predictive factors of cisplatin tolerance remain to be elucidated. The present study retrospectively reviewed newly diagnosed HNSCC patients who received CCRT. Cisplatin (80 mg/m2) was administered every 3 weeks. The proportion of high-dose cisplatin-tolerant patients (cumulative cisplatin dose, ≥200 mg/m2) was determined, and the predictive factors of cisplatin tolerance were analyzed in a logistic regression analysis. Between June 2006 and March 2013, a total of 159 patients were treated with CCRT. The median follow-up time was 36.7 months. A total of 73 patients (46%) tolerated a cumulative cisplatin dose ≥200 mg/m2; male gender [odds ratio (OR), 25.00; P=0.005] and high body surface area (BSA) (>1.80 m2; OR, 2.21; P=0.032) were significantly predictive of high-dose cisplatin tolerance. The high-dose cisplatin-tolerant patients had a significantly higher complete response (CR) rate (82 vs. 67%, P=0.045); however, there were no significant between-group differences in the 3-year OS (79.5 vs. 81.2%, P=0.59) or PFS (70.4 vs. 44.6%, P=0.076) by cisplatin tolerance. In clinical practice, approximately one-half of the patients tolerated high-dose cisplatin in CCRT. Male gender and high BSA could be predictive of cisplatin tolerance. PMID:26893880

Parotid Glands Dose–Effect Relationships Based on Their Actually Delivered Doses: Implications for Adaptive Replanning in Radiation Therapy of Head-and-Neck Cancer

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

Hunter, Klaudia U.; Fernandes, Laura L.; Vineberg, Karen A.

2013-11-15

Purpose: Doses actually delivered to the parotid glands during radiation therapy often exceed planned doses. We hypothesized that the delivered doses correlate better with parotid salivary output than the planned doses, used in all previous studies, and that determining these correlations will help make decisions regarding adaptive radiation therapy (ART) aimed at reducing the delivered doses. Methods and Materials: In this prospective study, oropharyngeal cancer patients treated definitively with chemoirradiation underwent daily cone-beam computed tomography (CBCT) with clinical setup alignment based on the C2 posterior edge. Parotid glands in the CBCTs were aligned by deformable registration to calculate cumulative deliveredmore » doses. Stimulated salivary flow rates were measured separately from each parotid gland pretherapy and periodically posttherapy. Results: Thirty-six parotid glands of 18 patients were analyzed. Average mean planned doses was 32 Gy, and differences from planned to delivered mean gland doses were −4.9 to +8.4 Gy, median difference +2.2 Gy in glands in which delivered doses increased relative to planned. Both planned and delivered mean doses were significantly correlated with posttreatment salivary outputs at almost all posttherapy time points, without statistically significant differences in the correlations. Large dispersions (on average, SD 3.6 Gy) characterized the dose–effect relationships for both. The differences between the cumulative delivered doses and planned doses were evident at first fraction (r=.92, P<.0001) because of complex setup deviations (eg, rotations and neck articulations), uncorrected by the translational clinical alignments. Conclusions: After daily translational setup corrections, differences between planned and delivered doses in most glands were small relative to the SDs of the dose–saliva data, suggesting that ART is not likely to gain measurable salivary output improvement in most cases. These differences were observed at first treatment, indicating potential benefit for more complex setup corrections or adaptive interventions in the minority of patients with large deviations detected early by CBCT.« less

An Increased Risk of Reversible Dementia May Occur After Zolpidem Derivative Use in the Elderly Population

PubMed Central

Shih, Hsin-I; Lin, Che-Chen; Tu, Yi-Fang; Chang, Chia-Ming; Hsu, Hsiang-Chin; Chi, Chih-Hsien; Kao, Chia-Hung

2015-01-01

Abstract We evaluate the effects of zolpidem use to develop dementia or Alzheimer disease from the Taiwan National Health Insurance Research Database (NHIRD). A retrospective population-based nested case–control study. Newly diagnosed dementia patients 65 years and older and controls were sampled. A total of 8406 dementia and 16,812 control subjects were enrolled from Taiwan NHIRD during 2006 to 2010. The relationships between zolpidem use and dementia were measured using odds and adjusted odds ratios. The relationship between the average cumulative doses for zolpidem and dementia was also analyzed. Zolpidem alone or with other underlying diseases, such as hypertension, diabetes, and stroke, was significantly associated with dementia after controlling for potential confounders, such as age, sex, coronary artery disease, diabetes, anti-hypertension drugs, stroke, anticholesterol statin drugs, depression, anxiety, benzodiazepine, anti-psychotic, and anti-depressant agents’ use (Adjusted OR = 1.33, 95% CI 1.24–1.41). Zolpidem use also has significant dose–response effects for most of the types of dementia. In patient with Alzheimer diseases, the effects of zolpidem among patients with Alzheimer's disease remained obscure. The adjusted OR for patients whose cumulative exposure doses were between 170 and 819 mg/year (adjusted OR: 1.65, 95% CI 1.08–2.51, P = 0.0199) was significant; however, the effects for lower and higher cumulative dose were not significant. Zolpidem used might be associated with increased risk for dementia in elderly population. Increased accumulative dose might have higher risk to develop dementia, especially in patients with underlying diseases such as hypertension, diabetes, and stroke. PMID:25929937

Effect of age and lactose on sup 67 Cu utilization in rats

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

Link, J.; Dowdy, R.; Michelmann, E.

1991-03-15

Young and old male Fischer 344 rats were fed a control diet or a lactose diet. After four weeks rats were gavaged with approximately 6.24 uCl {sup 67}Cu, placed in metabolism cages, and fed their respective diets for an additional two weeks. Daily whole body, urine and fecal radioactivity measurements were made. Rats were killed on day 42 and livers removed for radioactivity determination. Diet had no effect on whole body retention of {sup 67}Cu in the old rats; approximately 20% of the initial dose was retained by the end of the study. In the young rats, however, lactose appearedmore » to enhance initial {sup 67}Cu retention; by day three young control rats retained only 30% of the initial dose, while the young lactose rats retained about 50%. Retention of {sup 67}Cu at the end of the study was approximately 15% and 20% for young control and young lactose rats, respectively. During the first four days post dosing, cumulative fecal {sup 67}Cu excretion was approximately 83% for young control rats and 69% for young lactose rats indicating enhancement of {sup 67}Cu absorption by lactose in the young rats. For old rats cumulative {sup 67}Cu excretion in feces was about 50% regardless of diet. Cumulative urinary {sup 67}Cu excretion was approximately 6% and 8% for young control and lactose rats, respectively vs about 11% for old rats. {sup 67}Cu retention in liver was greater in old rats regardless of diet. The early increase in {sup 67}Cu absorption after a bolus dose may have therapeutic implications. In light of current concern regarding Cu-carbohydrate interactions, the apparent enhancement Cu retention by lactose in young rats deserves further attention.« less

Beyond the Dose-Limiting Toxicity Period: Dermatologic Adverse Events of Patients on Phase 1 Trials of the Cancer Therapeutics Evaluation Program

PubMed Central

Drilon, Alexander; Eaton, Anne A.; Schindler, Katja; Gounder, Mrinal M.; Spriggs, David R.; Harris, Pamela; Ivy, S. Percy; Iasonos, Alexia; Lacouture, Mario E.; Hyman, David M.

2017-01-01

BACKGROUND Dermatologic adverse events (AEs) can be key determinants of overall drug tolerability and of the maximum tolerated and recommended phase 2 doses in phase 1 trials. The authors present the largest dedicated analysis of dermatologic AEs on phase 1 trials to date. METHODS Data from a prospectively maintained database of patients with solid tumors who were enrolled onto Cancer Therapeutics Evaluation Program (CTEP)-sponsored phase 1 trials of cytotoxic or molecularly targeted agents (MTAs) from 2000 to 2010 were analyzed. Cumulative incidence, site, and type of drug-related dermatologic AEs were described and compared. The timing of worst drug-related dermatologic AEs was summarized. RESULTS In total, 3517 patients with solid tumors and 6165 unique, drug-related dermatologic AEs were analyzed, including 1545 patients on MTA-only trials, 671 on cytotoxic-only trials, and 1392 on combination MTA and cytotoxic trials. Of 1270 patients who had drug-related dermatologic events, the timing of the worst AE was as follows: 743 (cycle 1), 303 (cycle 2), and 224 (cycle 3 or later). Although the cumulative incidence of grade ≥3 drug-related AEs increased to 2.4% by cycle 6, it was only 1.6% at the end of cycle 1. The cumulative incidence of drug-related AEs was highest in patients who received MTA-only therapy (P <.001) and differed by dose level (P <.001). In patients who received MTA-only therapy, drug-related AEs were most common for combination kinase inhibitor-containing therapy (P <.001). CONCLUSIONS A substantial proportion of drug-related dermatologic AEs occur after the traditional dose-limiting toxicity monitoring period of phase 1 clinical trials. Future designs should account for late toxicities. PMID:26916138

Beyond the dose-limiting toxicity period: Dermatologic adverse events of patients on phase 1 trials of the Cancer Therapeutics Evaluation Program.

PubMed

Drilon, Alexander; Eaton, Anne A; Schindler, Katja; Gounder, Mrinal M; Spriggs, David R; Harris, Pamela; Ivy, S Percy; Iasonos, Alexia; Lacouture, Mario E; Hyman, David M

2016-04-15

Dermatologic adverse events (AEs) can be key determinants of overall drug tolerability and of the maximum tolerated and recommended phase 2 doses in phase 1 trials. The authors present the largest dedicated analysis of dermatologic AEs on phase 1 trials to date. Data from a prospectively maintained database of patients with solid tumors who were enrolled onto Cancer Therapeutics Evaluation Program (CTEP)-sponsored phase 1 trials of cytotoxic or molecularly targeted agents (MTAs) from 2000 to 2010 were analyzed. Cumulative incidence, site, and type of drug-related dermatologic AEs were described and compared. The timing of worst drug-related dermatologic AEs was summarized. In total, 3517 patients with solid tumors and 6165 unique, drug-related dermatologic AEs were analyzed, including 1545 patients on MTA-only trials, 671 on cytotoxic-only trials, and 1392 on combination MTA and cytotoxic trials. Of 1270 patients who had drug-related dermatologic events, the timing of the worst AE was as follows: 743 (cycle 1), 303 (cycle 2), and 224 (cycle 3 or later). Although the cumulative incidence of grade ≥3 drug-related AEs increased to 2.4% by cycle 6, it was only 1.6% at the end of cycle 1. The cumulative incidence of drug-related AEs was highest in patients who received MTA-only therapy (P < .001) and differed by dose level (P < .001). In patients who received MTA-only therapy, drug-related AEs were most common for combination kinase inhibitor-containing therapy (P < .001). A substantial proportion of drug-related dermatologic AEs occur after the traditional dose-limiting toxicity monitoring period of phase 1 clinical trials. Future designs should account for late toxicities. © 2016 American Cancer Society.

Liraglutide, leptin, and their combined effects on feeding: additive intake reduction through common intracellular signaling mechanisms

PubMed Central

Kanoski, Scott E.; Ong, Zhi Yi; Fortin, Samantha M.; Schlessinger, Elizabeth S.; Grill, Harvey J.

2014-01-01

Aims Glucagon like peptide-1 receptor (GLP-1R) agonists and leptin each exert anorexigenic effects. In combination, the intake inhibitory and weight loss effects are greater than either treatment alone, however the mechanisms unclear. Materials and methods Effects of liraglutide (a long-acting GLP-1 analogue) and leptin co-treatment, delivered in low or moderate doses subcutaneously (SC) or to the 3rd ventricle respectively, on cumulative intake, meal patterns, and hypothalamic expression of intracellular signaling proteins [phosphorylated signal transducer and activator of transcription-3 (pSTAT3) and protein tyrosine phosphatase-1B (PTP1B)] were examined in lean rats. Results A low-dose combination of liraglutide (25μg/kg) and leptin (0.75μg) additively reduced cumulative food intake and body weight, a result mediated predominantly through a significant reduction in meal frequency that was not present with either drug alone. Liraglutide treatment alone also reduced meal size; an effect not enhanced with leptin co-administration. Moderate doses of liraglutide (75μg/kg) and leptin (4μg) examined separately each reduced meal frequency, cumulative food intake, and body weight; only liraglutide reduced meal size. In combination these doses did not further enhance the anorexigenic effects of either treatment alone. Ex vivo immunoblot showed elevated pSTAT3 in hypothalamic tissue following liraglutide-leptin co-treatment, an effect greater than leptin treatment alone. In addition, SC liraglutide reduced expression of PTP1B (a negative regulator of leptin receptor signaling), revealing a potential mechanism for the enhanced pSTAT3 response following liraglutide-leptin co-administration. Conclusions Collectively, these results provide novel behavioral and molecular mechanisms underlying the additive reduction in food intake and body weight following liraglutide-leptin combination treatment. PMID:25475828

Comparison of fluoro and cine coronary angiography: balancing acceptable outcomes with a reduction in radiation dose.

PubMed

Olcay, Ayhan; Guler, Ekrem; Karaca, Ibrahim Oguz; Omaygenc, Mehmet Onur; Kizilirmak, Filiz; Olgun, Erkam; Yenipinar, Esra; Cakmak, Huseyin Altug; Duman, Dursun

2015-04-01

Use of last fluoro hold (LFH) mode in fluoroscopy, which enables the last live image to be saved and displayed, could reduce radiation during percutaneous coronary intervention when compared with cine mode. No previous study compared coronary angiography radiation doses and image quality between LFH and conventional cine mode techniques. We compared cumulative dose-area product (DAP), cumulative air kerma, fluoroscopy time, contrast use, interobserver variability of visual assessment between LFH angiography, and conventional cine angiography techniques. Forty-six patients were prospectively enrolled into the LFH group and 82 patients into the cine angiography group according to operator decision. Mean cumulative DAP was higher in the cine group vs the LFH group (50058.98 ± 53542.71 mGy•cm² vs 11349.2 ± 8796.46 mGy•cm²; P<.001). Mean fluoroscopy times were higher in the cine group vs the LFH group (3.87 ± 5.08 minutes vs 1.66 ± 1.51 minutes; P<.01). Mean contrast use was higher in the cine group vs the LFH group (112.07 ± 43.79 cc vs 88.15 ± 23.84 cc; P<.001). Mean value of Crombach's alpha was not statistically different between visual estimates of three operators between cine and LFH angiography groups (0.66680 ± 0.19309 vs 0.54193 ± 0.31046; P=.20). Radiation doses, contrast use, and fluoroscopy times are lower in fluoroscopic LFH angiography vs cine angiography. Interclass variability of visual stenosis estimation between three operators was not different between cine and LFH groups. Fluoroscopic LFH images conventionally have inferior diagnostic quality when compared with cine coronary angiography, but with new angiographic systems with improved LFH image quality, these images may be adequate for diagnostic coronary angiography.

Effects of early exposure and lifetime exposure to intimate partner violence (IPV) on child adjustment.

PubMed

Graham-Bermann, Sandra A; Perkins, Suzanne

2010-01-01

Children exposed to overwhelming and potentially traumatic events early in their lives are considered at-risk for problems in adjustment. Yet it is not known whether it is the age of first exposure (AFE) to violence or the amount of violence that the child witnessed in their lifetime that has the greatest impact on adjustment. For a sample of 190 children ages 6 to 12 exposed to intimate partner violence, their mothers reported that the average length of their abusive relationship was 10 years. The majority of children were first exposed to family violence as infants (64%), with only 12% first exposed when school-aged. Both the AFE and an estimate of the cumulative amount of violence were significantly and negatively related to children's behavioral problems. However, in regression analyses controlling for child sex, ethnicity, age, and family environment variables, cumulative violence exposure accounted for greater variance in adjustment than did AFE. Furthermore, cumulative violence exposure mediated the relationship between AFE and externalizing behavior problems, indicating that the cumulative exposure to IPV outweighed the AFE in its effect on child adjustment.

Retrospective Evaluation Reveals That Long-term Androgen Deprivation Therapy Improves Cause-Specific and Overall Survival in the Setting of Dose-Escalated Radiation for High-Risk Prostate Cancer

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

Feng, Felix Y., E-mail: ffeng@med.umich.edu; Department of Radiation Oncology, Veterans Affairs Medical Center, Ann Arbor, Michigan; Blas, Kevin

2013-05-01

Purpose: To evaluate the role of androgen deprivation therapy (ADT) and duration for high-risk prostate cancer patients treated with dose-escalated radiation therapy (RT). Methods and Materials: A retrospective analysis of high-risk prostate cancer patients treated with dose-escalated RT (minimum 75 Gy) with or without ADT was performed. The relationship between ADT use and duration with biochemical failure (BF), metastatic failure (MF), prostate cancer-specific mortality (PCSM), non-prostate cancer death (NPCD), and overall survival (OS) was assessed as a function of pretreatment characteristics, comorbid medical illness, and treatment using Fine and Gray's cumulative incidence methodology. Results: The median follow-up time was 64more » months. In men with National Comprehensive Cancer Network defined high-risk prostate cancer treated with dose-escalated RT, on univariate analysis, both metastasis (P<.0001; hazard ratio 0.34; 95% confidence interval 0.18-0.67; cumulative incidence at 60 months 13% vs 35%) and PCSM (P=.015; hazard ratio 0.41; 95% confidence interval 0.2-1.0; cumulative incidence at 60 months 6% vs 11%) were improved with the use of ADT. On multivariate analysis for all high-risk patients, Gleason score was the strongest negative prognostic factor, and long-term ADT (LTAD) improved MF (P=.002), PCSM (P=.034), and OS (P=.001). In men with prostate cancer and Gleason scores 8 to 10, on multivariate analysis after adjustment for other risk features, there was a duration-dependent improvement in BF, metastasis, PCSM, and OS, all favoring LTAD in comparison with STAD or RT alone. Conclusion: For men with high-risk prostate cancer treated with dose-escalated EBRT, this retrospective study suggests that the combination of LTAD and RT provided a significant improvement in clinical outcome, which was especially true for those with Gleason scores of 8 to 10.« less

Comparison of measured and estimated maximum skin doses during CT fluoroscopy lung biopsies.

PubMed

Zanca, F; Jacobs, A; Crijns, W; De Wever, W

2014-07-01

To measure patient-specific maximum skin dose (MSD) associated with CT fluoroscopy (CTF) lung biopsies and to compare measured MSD with the MSD estimated from phantom measurements, as well as with the CTDIvol of patient examinations. Data from 50 patients with lung lesions who underwent a CT fluoroscopy-guided biopsy were collected. The CT protocol consisted of a low-kilovoltage (80 kV) protocol used in combination with an algorithm for dose reduction to the radiology staff during the interventional procedure, HandCare (HC). MSD was assessed during each intervention using EBT2 gafchromic films positioned on patient skin. Lesion size, position, total fluoroscopy time, and patient-effective diameter were registered for each patient. Dose rates were also estimated at the surface of a normal-size anthropomorphic thorax phantom using a 10 cm pencil ionization chamber placed at every 30°, for a full rotation, with and without HC. Measured MSD was compared with MSD values estimated from the phantom measurements and with the cumulative CTDIvol of the procedure. The median measured MSD was 141 mGy (range 38-410 mGy) while the median cumulative CTDIvol was 72 mGy (range 24-262 mGy). The ratio between the MSD estimated from phantom measurements and the measured MSD was 0.87 (range 0.12-4.1) on average. In 72% of cases the estimated MSD underestimated the measured MSD, while in 28% of the cases it overestimated it. The same trend was observed for the ratio of cumulative CTDIvol and measured MSD. No trend was observed as a function of patient size. On average, estimated MSD from dose rate measurements on phantom as well as from CTDIvol of patient examinations underestimates the measured value of MSD. This can be attributed to deviations of the patient's body habitus from the standard phantom size and to patient positioning in the gantry during the procedure.

Oral Squamous Cell Carcinoma Found Inline with the Fields of Repeat Stereotactic Radiosurgery for Recurrent Trigeminal Neuralgia.

PubMed

Berti, Aldo; Granville, Michelle; Jacobson, Robert E

2018-01-12

A case of an extremely healthy, active, 96-year-old patient, nonsmoker, is reviewed. He was initially treated for left V1, V2, and V3 trigeminal neuralgia in 2001, at age 80, with stereotactic radiosurgery (SRS) with a dose of 80 Gy to the left retrogasserian trigeminal nerve. He remained asymptomatic for nine years until his trigeminal pain recurred in 2010. He was first treated medically but was intolerant to increasing doses of carbamazepine and gabapentin. He underwent a second SRS in 2012 with a dose of 65.5 Gy to the same retrogasserian area of the trigeminal nerve, making the total cumulative dose 125.5 Gy. In late 2016, four years after the 2 nd SRS, he was found to have invasive keratinizing squamous cell carcinoma in the left posterior mandibular oral mucosa. Keratinizing squamous cell carcinoma is seen primarily in smokers or associated with the human papillomavirus, neither of which was found in this patient. A review of his two SRS plans shows that the left lower posterior mandibular area was clearly within the radiation fields for both SRS treatments. It is postulated that his cancer developed secondary to the long-term radiation effect with a very localized area being exposed twice to a focused, cumulative, high-dose radiation. There are individual reports in the literature of oral mucositis immediately after radiation for trigeminal neuralgia and the delayed development of malignant tumors, including glioblastoma found after SRS for acoustic neuromas, but there are no reports of delayed malignant tumors developing within the general radiation field. Using repeat SRS is an accepted treatment for recurrent trigeminal neuralgia, but physicians and patients should be aware of the potential effects of higher cumulative radiation effects within the treatment field when patients undergo repeat procedures.

Intracranial meningiomas related to external cranial irradiation

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

Spallone, A.; Gagliardi, F.M.; Vagnozzi, R.

1979-08-01

Three cases are presented of meningiomas following small-dose external cranial irradiation in which several features clearly indicate a causal relationship between radiotherapy and tumor development. The length of the latent period separates meningiomas following high-dose irradiation from those which followed small-dose irradiation. Therefore the oncogenic mechanism seems to act differently in the two groups. This demonstration that multiple meningiomas can occur in patients irradiated for Tinea capitis should enable other similar cases to be recognized.

Cost and Effectiveness of Decontamination Strategies in Radiation Contaminated Areas in Fukushima in Regard to External Radiation Dose

PubMed Central

Yasutaka, Tetsuo; Naito, Wataru; Nakanishi, Junko

2013-01-01

The objective of the present study is to evaluate the cost and effectiveness of decontamination strategies in the special decontamination areas in Fukushima in regard to external radiation dose. A geographical information system (GIS) was used to relate the predicted external dose in the affected areas to the number of potential inhabitants and the land use in the areas. A comprehensive review of the costs of various decontamination methods was conducted as part of the analysis. The results indicate that aerial decontamination in the special decontamination areas in Fukushima would be effective for reducing the air dose rate to the target level in a short period of time in some but not all of the areas. In a standard scenario, analysis of cost and effectiveness suggests that decontamination costs for agricultural areas account for approximately 80% of the total decontamination cost, of which approximately 60% is associated with storage. In addition, the costs of decontamination per person per unit area are estimated to vary greatly. Appropriate selection of decontamination methods may significantly decrease decontamination costs, allowing more meaningful decontamination in terms of the limited budget. Our analysis can help in examining the prioritization of decontamination areas from the viewpoints of cost and effectiveness in reducing the external dose. Decontamination strategies should be determined according to air dose rates and future land-use plans. PMID:24069398

Cost and effectiveness of decontamination strategies in radiation contaminated areas in Fukushima in regard to external radiation dose.

PubMed

Yasutaka, Tetsuo; Naito, Wataru; Nakanishi, Junko

2013-01-01

The objective of the present study is to evaluate the cost and effectiveness of decontamination strategies in the special decontamination areas in Fukushima in regard to external radiation dose. A geographical information system (GIS) was used to relate the predicted external dose in the affected areas to the number of potential inhabitants and the land use in the areas. A comprehensive review of the costs of various decontamination methods was conducted as part of the analysis. The results indicate that aerial decontamination in the special decontamination areas in Fukushima would be effective for reducing the air dose rate to the target level in a short period of time in some but not all of the areas. In a standard scenario, analysis of cost and effectiveness suggests that decontamination costs for agricultural areas account for approximately 80% of the total decontamination cost, of which approximately 60% is associated with storage. In addition, the costs of decontamination per person per unit area are estimated to vary greatly. Appropriate selection of decontamination methods may significantly decrease decontamination costs, allowing more meaningful decontamination in terms of the limited budget. Our analysis can help in examining the prioritization of decontamination areas from the viewpoints of cost and effectiveness in reducing the external dose. Decontamination strategies should be determined according to air dose rates and future land-use plans.

Action spectrum for phototherapy of psoriasis

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

Parrish, J.A.; Jaenicke, K.F.

1981-05-01

Using a monochromator the action spectrum for ultraviolet phototherapy of psoriasis was determined for radiation between 254 and 313 nm and compared to the action spectrum for erythema of uninvolved adjacent skin. Daily exposures of different doses of 254, 280, 290, 296, 300, 304 and 313 nm radiation were observed. Wavelengths of 254, 280, 290 nm were erythemogenic but not therapeutic even at 10 to 50 times the minimal erythema dose. At the other wavelengths studied, the 2 action spectra were similar. In general, fixed daily doses cleared at lower cumulative dose than did incrementally increased daily doses. The smallmore » number of suberythemogenic exposure doses required suggests that monochromatic radiation may have advantages over broadband sources.« less

10 CFR 835.203 - Combining internal and external equivalent doses.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Combining internal and external equivalent doses. 835.203 Section 835.203 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and... the radiation and tissue weighting factor values provided in § 835.2. [72 FR 31926, June 8, 2007] ...

10 CFR 835.203 - Combining internal and external equivalent doses.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Combining internal and external equivalent doses. 835.203 Section 835.203 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and... the radiation and tissue weighting factor values provided in § 835.2. [72 FR 31926, June 8, 2007] ...

10 CFR 835.203 - Combining internal and external equivalent doses.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Combining internal and external equivalent doses. 835.203 Section 835.203 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and... the radiation and tissue weighting factor values provided in § 835.2. [72 FR 31926, June 8, 2007] ...

10 CFR 835.203 - Combining internal and external equivalent doses.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Combining internal and external equivalent doses. 835.203 Section 835.203 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and... the radiation and tissue weighting factor values provided in § 835.2. [72 FR 31926, June 8, 2007] ...

Doses from external irradiation to Marshall Islanders from Bikini and Enewetak nuclear weapons tests.

PubMed

Bouville, André; Beck, Harold L; Simon, Steven L

2010-08-01

Annual doses from external irradiation resulting from exposure to fallout from the 65 atmospheric nuclear weapons tests conducted in the Marshall Islands at Bikini and Enewetak between 1946 and 1958 have been estimated for the first time for Marshallese living on all inhabited atolls. All tests that deposited fallout on any of the 23 inhabited atolls or separate reef islands have been considered. The methodology used to estimate the radiation doses at the inhabited atolls is based on test- and location-specific radiation survey data, deposition density estimates of 137Cs, and fallout times-of-arrival provided in a companion paper (Beck et al.), combined with information on the radionuclide composition of the fallout at various times after each test. These estimates of doses from external irradiation have been combined with corresponding estimates of doses from internal irradiation, given in a companion paper (Simon et al.), to assess the cancer risks among the Marshallese population (Land et al.) resulting from exposure to radiation from the nuclear weapons tests.

Non-Chemical Stressors and Cumulative Risk Assessment: An Overview of Current Initiatives and Potential Air Pollutant Interactions

PubMed Central

Lewis, Ari S.; Sax, Sonja N.; Wason, Susan C.; Campleman, Sharan L.

2011-01-01

Regulatory agencies are under increased pressure to consider broader public health concerns that extend to multiple pollutant exposures, multiple exposure pathways, and vulnerable populations. Specifically, cumulative risk assessment initiatives have stressed the importance of considering both chemical and non-chemical stressors, such as socioeconomic status (SES) and related psychosocial stress, in evaluating health risks. The integration of non-chemical stressors into a cumulative risk assessment framework has been largely driven by evidence of health disparities across different segments of society that may also bear a disproportionate risk from chemical exposures. This review will discuss current efforts to advance the field of cumulative risk assessment, highlighting some of the major challenges, discussed within the construct of the traditional risk assessment paradigm. Additionally, we present a summary of studies of potential interactions between social stressors and air pollutants on health as an example of current research that supports the incorporation of non-chemical stressors into risk assessment. The results from these studies, while suggestive of possible interactions, are mixed and hindered by inconsistent application of social stress indicators. Overall, while there have been significant advances, further developments across all of the risk assessment stages (i.e., hazard identification, exposure assessment, dose-response, and risk characterization) are necessary to provide a scientific basis for regulatory actions and effective community interventions, particularly when considering non-chemical stressors. A better understanding of the biological underpinnings of social stress on disease and implications for chemical-based dose-response relationships is needed. Furthermore, when considering non-chemical stressors, an appropriate metric, or series of metrics, for risk characterization is also needed. Cumulative risk assessment research will benefit from coordination of information from several different scientific disciplines, including, for example, toxicology, epidemiology, nutrition, neurotoxicology, and the social sciences. PMID:21776216

Dose Calculations for [131I] Meta-Iodobenzylguanidine-Induced Bystander Effects

PubMed Central

Gow, M. D.; Seymour, C. B.; Boyd, M.; Mairs, R. J.; Prestiwch, W. V.; Mothersill, C. E.

2014-01-01

Targeted radiotherapy is a potentially useful treatment for some cancers and may be potentiated by bystander effects. However, without estimation of absorbed dose, it is difficult to compare the effects with conventional external radiation treatment. Methods: Using the Vynckier – Wambersie dose point kernel, a model for dose rate evaluation was created allowing for calculation of absorbed dose values to two cell lines transfected with the noradrenaline transporter (NAT) gene and treated with [131I]MIBG. Results: The mean doses required to decrease surviving fractions of UVW/NAT and EJ138/NAT cells, which received medium from [131I]MIBG-treated cells, to 25 – 30% were 1.6 and 1.7 Gy respectively. The maximum mean dose rates achieved during [131I]MIBG treatment were 0.09 – 0.75 Gy/h for UVW/NAT and 0.07 – 0.78 Gy/h for EJ138/NAT. These were significantly lower than the external beam gamma radiation dose rate of 15 Gy/h. In the case of control lines which were incapable of [131I]MIBG uptake the mean absorbed doses following radiopharmaceutical were 0.03 – 0.23 Gy for UVW and 0.03 – 0.32 Gy for EJ138. Conclusion: [131I]MIBG treatment for ICCM production elicited a bystander dose-response profile similar to that generated by external beam gamma irradiation but with significantly greater cell death. PMID:24659931

Development of In Vitro-In Vivo Correlation for Potassium Chloride Extended Release Tablet Formulation Using Urinary Pharmacokinetic Data.

PubMed

Mittapalli, Rajendar K; Marroum, Patrick; Qiu, Yihong; Apfelbaum, Kathleen; Xiong, Hao

2017-07-01

To develop and validate a Level A in vitro-in vivo correlation (IVIVC) for potassium chloride extended-release (ER) formulations. Three prototype ER formulations of potassium chloride with different in vitro release rates were developed and their urinary pharmacokinetic profiles were evaluated in healthy subjects. A mathematical model between in vitro dissolution and in vivo urinary excretion, a surrogate for measuring in vivo absorption, was developed using time-scale and time-shift parameters. The IVIVC model was then validated based on internal and external predictability. With the established IVIVC model, there was a good correlation between the observed fraction of dose excreted in urine and the time-scaled and time-shifted fraction of the drug dissolved, and between the in vitro dissolution time and the in vivo urinary excretion time for the ER formulations. The percent prediction error (%PE) on cumulative urinary excretion over the 24 h interval (A e0-24h ) and maximum urinary excretion rate (R max ) was less than 15% for the individual formulations and less than 10% for the average of the two formulations used to develop the model. Further, the %PE values using external predictability were below 10%. A novel Level A IVIVC was successfully developed and validated for the new potassium chloride ER formulations using urinary pharmacokinetic data. This successful IVIVC may facilitate future development or manufacturing changes to the potassium chloride ER formulation.

Population dose near the Semipalatinsk test site.

PubMed

Hille, R; Hill, P; Bouisset, P; Calmet, D; Kluson, J; Seisebaev, A; Smagulov, S

1998-10-01

To determine the consequences of atmospheric atomic bomb tests for the population in the surroundings of the former nuclear weapons test site near Semipalatinsk in Kazakhstan, a pilot study was performed by an international cooperation between Kazakh, French, Czech and German institutions at two villages, Mostik and Maisk. Together with Kazakh scientists, eight experts from Europe carried out a field mission in September 1995 to assess, within the framework of a NATO supported project, the radiological situation as far as external doses, environmental contamination and body burden of man were concerned. A summary of the results obtained is presented. The actual radiological situation near the test site is characterized by fallout contaminations. Cs was found in upper soil layers in concentrations similar to those of the global fallout. Also Sr, Am and Co were observed. The resulting present dose to the population is low. Mean external doses from soil contamination for Maisk and Mostik (0.60-0.63 mSv/year) presently correspond to mean external doses in normal environments. Mean values of the annual internal doses observed in these two villages are below 2 microSv/year for 90Sr. For other radionuclides the internal doses are also negligible.

Is the use of the cervical vertebrae maturation method justified to determine skeletal age? A comparison of radiation dose of two strategies for skeletal age estimation.

PubMed

Patcas, Raphael; Signorelli, Luca; Peltomäki, Timo; Schätzle, Marc

2013-10-01

The aim of this study was to assess effective doses of a lateral cephalogram radiograph with and without thyroid shield and compare the differences with the radiation dose of a hand-wrist radiograph. Thermoluminescent dosimeters were placed at 19 different sites in the head and neck of a tissue-equivalent human skull (RANDO phantom). Analogue lateral cephalograms with and without thyroid shield (67 kV, 250 mA, 10 mAs) and hand-wrist radiographs (40 kV, 250 mA, 10 mAs) were obtained. The effective doses were calculated using the 2007 International Commission on Radiological Protection recommendations. The effective dose for conventional lateral cephalogram without a thyroid shield was 5.03 microsieverts (µSv). By applying a thyroid shield to the RANDO phantom, a remarkable dose reduction of 1.73 µSv could be achieved. The effective dose of a conventional hand-wrist radiograph was calculated to be 0.16 µSv. Adding the effective dose of the hand-wrist radiograph to the effective dose of the lateral cephalogram with thyroid shield resulted in a cumulative effective dose of 3.46 µSv. Without thyroid shield, the effective dose of a lateral cephalogram was approximately 1.5-fold increased than the cumulative effective dose of a hand-wrist radiograph and a lateral cephalogram with thyroid shield. Thyroid is an organ that is very sensitive to radiation exposure. Its shielding will significantly reduce the effective dose. An additional hand-wrist radiograph, involving no vulnerable tissues, however, causes very little radiation risk. In accordance with the ALARA (As Low As Reasonably Achievable) principle, if an evaluation of skeletal age is indicated, an additional hand-wrist radiograph seems much more justifiable than removing the thyroid shield.

A simple 3-day "rush" venom immunotherapy protocol: documentation of safety.

PubMed

Kalogeromitros, D; Makris, M; Koti, I; Chliva, C; Mellios, A; Avgerinou, G; Theoharides, T C

2010-01-01

Venom immunotherapy (VIT) is the only effective treatment for hymenoptera hypersensitivity, but conventional protocols require a few weeks. We present the safety of a 3-day "rush" protocol that requires only 7 injections and 255 mgr cumulative dose before the 100 microg maintenance dose. Forty-nine patients (33 males, 16 females) of mean age 43.57+/-12.9 yrs received "rush" VIT. Only 7 injections were required until the maintenance dose of 100 mgr was reached on Day 5. On Day 1, four injections were administered with initial dose of 5 mgr and total dose of 75 microg. On Day 3 a cumulative dose of 180 mgr was administered in three injections (40 mgr, 60 mgr and 80 mgr). A dose of 100 mgr was administered on Day 5. Twenty-nine individuals were treated with Honey-Bee venom; 18 with Common wasp; 5 with Paper Wasp; while 13 patients received Mixed Vespid preparation. Inclusion criteria were documented IgE-mediated allergy with intradermal sensitivity to < or =0.1 mgr/ml venom concentration and concomitant detection of specific venom IgE > or =0.35 kU/l. All patients reached the maintenance dose. Forty-nine patients received 65 immunotherapy courses, resulting in 1520 injections. Thirty-three systemic reactions: 7 during building phase (1.5%); and 26 in the maintenance dose (2.4%) were observed in 9 patients. The percentage of reactions/total injection number was 2.2%; all reactions were mild-to-moderate. Fourteen patients reported documented field stings at least two months after VIT onset with only one reported mild systemic reaction. We propose a simple "rush" VIT protocol in an outpatient setting as an easy-to-perform alternative option for VIT induction phase. Copyright 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

Diagnostic radiation exposure in pediatric trauma patients.

PubMed

Brunetti, Marissa A; Mahesh, Mahadevappa; Nabaweesi, Rosemary; Locke, Paul; Ziegfeld, Susan; Brown, Robert

2011-02-01

The amount of imaging studies performed for disease diagnosis has been rapidly increasing. We examined the amount of radiation exposure that pediatric trauma patients receive because they are an at-risk population. Our hypothesis was that pediatric trauma patients are exposed to high levels of radiation during a single hospital visit. Retrospective review of children who presented to Johns Hopkins Pediatric Trauma Center from July 1, 2004, to June 30, 2005. Radiographic studies were recorded for each patient and doses were calculated to give a total effective dose of radiation. All radiographic studies that each child received during evaluation, including any associated hospital admission, were included. A total of 945 children were evaluated during the study year. A total of 719 children were included in the analysis. Mean age was 7.8 (±4.6) years. Four thousand six hundred three radiographic studies were performed; 1,457 were computed tomography (CT) studies (31.7%). Average radiation dose was 12.8 (±12) mSv. We found that while CT accounted for only 31.7% of the radiologic studies performed, it accounted for 91% of the total radiation dose. Mean dose for admitted children was 17.9 (±13.8) mSv. Mean dose for discharged children was 8.4 (±7.8) mSv (p<0.0001). Burn injuries had the lowest radiation dose [1.2 (±2.6) mSv], whereas motor vehicle collision victims had the highest dose [18.8 (±14.7) mSv]. When the use of radiologic imaging is considered essential, cumulative radiation exposure can be high. In young children with relatively long life spans, the benefit of each imaging study and the cumulative radiation dose should be weighed against the long-term risks of increased exposure.

Evaluation of effective dose for a patient under Ga-67 nuclear examination using TLD, water phantom and a simplified model

PubMed Central

Chu, Kuang Hua; Lin, Yu Ting; Hsu, Chia Chun; Chen, Chien Yi; Pan, Lung Kwang

2012-01-01

This study evaluated the effective dose of Ga-67 for a patient undergoing Ga-67 citrate nuclear examination by applying thermoluminescent dosimeter (TLD) technique and an indigenous water phantom. The Ga-67 radionuclide remaining in the body inevitably generated a measurable internal dose even though gamma camera scanning took only minutes to complete the clinical examination. For effective simulation of the cumulated effective dose for a patient undergoing examination, 150 TLDs were placed inside the water phantom for 6 days to monitor the gamma ray dose from the distributed Ga-67 citrate solution. The inserted TLDs represented internal organs, and the effective dose was calculated according to data in the ICRP-60 report. The water phantom was designed to model the body of a healthy human weighing 70 kg, and the water that was mixed with Ga-67 citrate solution was slowly replaced with fresh feed water to yield the required biological half life of the phantom. After continuously feeding in fresh water throughout the 6 days of TLD exposure, the TLDs were analyzed to determine the effective doses from the various biological half lives of the phantom. The derived effective dose of 185 MBq Ga-67 citrate solution for male/female (M/F) was 10.7/12.2, 10.7/12.0, 8.7/9.9 and 6.0/6.8 mSv, of biological half lives of 6.0, 4.5, 3.0 and 1.5 days, respectively. Although these experimental results correlated well with earlier empirical studies, they were lower than most calculated values. The cumulated uncertainty in the effective dose was 12.5–19.4%, which was acceptable in terms of both TLD counting statistic and reproducibility. PMID:22915780

A 1-year trial of repeated high-dose intravenous iron isomaltoside 1000 to maintain stable hemoglobin levels in inflammatory bowel disease.

PubMed

Reinisch, Walter; Altorjay, Istvan; Zsigmond, Ferenc; Primas, Christian; Vogelsang, Harald; Novacek, Gottfried; Reinisch, Sieglinde; Thomsen, Lars L

2015-01-01

Iron isomaltoside 1000 (Monofer®) is a high-dose intravenous (IV) iron, which in a recent 8 weeks trial in inflammatory bowel disease (IBD) subjects with iron deficiency anemia (IDA) demonstrated good tolerability and efficacy. The present trial is an extension to this trial, which evaluates the need for additional high IV iron doses to maintain a stable hemoglobin (Hb) ≥12.0 g/dl. This was a prospective, open-label, 12 months trial of European IBD subjects willing to participate after completing the lead-in trial. Subjects were allowed re-dosing with 500-2000 mg single doses of iron isomaltoside 1000 infused over ∼15 min at 3 months intervals depending on a predefined algorithm. Outcome measures included Hb, safety parameters and need for additional iron dosing. A total of 39 subjects were enrolled of which 34 subjects required re-dosing with a median cumulative 1-year dose of 1.8 g (mean cumulative dose 2.2 g). The mean (SD) Hb was 12.3 (1.5) g/dl at baseline, 12.8 (1.6) g/dl at 3 months, 12.8 (1.6) g/dl at 6 months, 12.9 (1.4) g/dl at 9 months and 12.9 (1.6) g/dl at 12 months. Seventy-four percent of subjects who had an Hb ≥12.0 g/dl at baseline were able to maintain Hb ≥12.0 g/dl till the end of the trial at 12 months. Nonserious probably related hypersensitivity reactions without significant hypotension were reported at the beginning of the infusion in two subjects, who recovered without sequelae. Repeated treatment of iron deficiency with iron isomaltoside 1000 could avoid episodes of IDA without major safety issues.

75 FR 44815 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-29

... title of the information collection: NRC Form 4, ``Cumulative Occupational Dose History''. 2. Current... minimized, including the use of automated collection techniques or other forms of information technology? A...

Ischaemic heart disease incidence and mortality in an extended cohort of Mayak workers first employed in 1948–1982

PubMed Central

Grigoryeva, Evgeniya S; Haylock, Richard G E; Pikulina, Maria V; Moseeva, Maria B

2015-01-01

Objective: Incidence and mortality from ischaemic heart disease (IHD) was studied in an extended cohort of 22,377 workers first employed at the Mayak Production Association during 1948–82 and followed up to the end of 2008. Methods: Relative risks and excess relative risks per unit dose (ERR/Gy) were calculated based on the maximum likelihood using Epicure software (Hirosoft International Corporation, Seattle, WA). Dose estimates used in analyses were provided by an updated “Mayak Worker Dosimetry System—2008”. Results: A significant increasing linear trend in IHD incidence with total dose from external γ-rays was observed after having adjusted for non-radiation factors and dose from internal radiation {ERR/Gy = 0.10 [95% confidence interval (CI): 0.04 to 0.17]}. The pure quadratic model provided a better fit of the data than did the linear one. No significant association of IHD mortality with total dose from external γ-rays after having adjusted for non-radiation factors and dose from internal alpha radiation was observed in the study cohort [ERR/Gy = 0.06 (95% CI: <0 to 0.15)]. A significant increasing linear trend was observed in IHD mortality with total absorbed dose from internal alpha radiation to the liver after having adjusted for non-radiation factors and dose from external γ-rays in both the whole cohort [ERR/Gy = 0.21 (95% CI: 0.01 to 0.58)] and the subcohort of workers exposed at alpha dose <1.00 Gy [ERR/Gy = 1.08 (95% CI: 0.34 to 2.15)]. No association of IHD incidence with total dose from internal alpha radiation to the liver was found in the whole cohort after having adjusted for non-radiation factors and external gamma dose [ERR/Gy = 0.02 (95% CI: not available to 0.10)]. Statistically significant dose effect was revealed in the subcohort of workers exposed to internal alpha radiation at dose to the liver <1.00 Gy [ERR/Gy = 0.44 (95% CI: 0.09 to 0.85)]. Conclusion: This study provides strong evidence of IHD incidence and mortality association with external γ-ray exposure and some evidence of IHD incidence and mortality association with internal alpha-radiation exposure. Advances in knowledge: It is the first time the validity of internal radiation dose estimates has been shown to affect the risk of IHD incidence. PMID:26224431

High brachytherapy doses can counteract hypoxia in cervical cancer—a modelling study

NASA Astrophysics Data System (ADS)

Lindblom, Emely; Dasu, Alexandru; Beskow, Catharina; Toma-Dasu, Iuliana

2017-01-01

Tumour hypoxia is a well-known adverse factor for the outcome of radiotherapy. For cervical tumours in particular, several studies indicate large variability in tumour oxygenation. However, clinical evidence shows that the management of cervical cancer including brachytherapy leads to high rate of success. It was the purpose of this study to investigate whether the success of brachytherapy for cervical cancer, seemingly regardless of oxygenation status, could be explained by the characteristics of the brachytherapy dose distributions. To this end, a previously used in silico model of tumour oxygenation and radiation response was further developed to simulate the treatment of cervical cancer employing a combination of external beam radiotherapy and intracavitary brachytherapy. Using a clinically-derived brachytherapy dose distribution and assuming a homogeneous dose delivered by external radiotherapy, cell survival was assessed on voxel level by taking into account the variation of sensitivity with oxygenation as well as the effects of repair, repopulation and reoxygenation during treatment. Various scenarios were considered for the conformity of the brachytherapy dose distribution to the hypoxic region in the target. By using the clinically-prescribed brachytherapy dose distribution and varying the total dose delivered with external beam radiotherapy in 25 fractions, the resulting values of the dose for 50% tumour control, D 50, were in agreement with clinically-observed values for high cure rates if fast reoxygenation was assumed. The D 50 was furthermore similar for the different degrees of conformity of the brachytherapy dose distribution to the tumour, regardless of whether the hypoxic fraction was 10%, 25%, or 40%. To achieve 50% control with external RT only, a total dose of more than 70 Gy in 25 fractions would be required for all cases considered. It can thus be concluded that the high doses delivered in brachytherapy can counteract the increased radioresistance caused by hypoxia if fast reoxygenation is assumed.

SU-C-BRD-06: Results From a 5 Patient in Vivo Rectal Wall Dosimetry Study Using Plastic Scintillation Detectors

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

Wootton, L; Kudchadker, R; Lee, A

Purpose: To evaluate the performance characteristics of plastic scintillation detectors (PSDs) in an in vivo environment for external beam radiation, and to establish the usefulness and ease of implementation of a PSD based in vivo dosimetry system for routine clinical use. Methods: A five patient IRB approved in vivo dosimetry study was performed. Five patients with prostate cancer were enrolled and PSDs were used to monitor rectal wall dose and verify the delivered dose for approximately two fractions each week over the course of their treatment (approximately fourteen fractions), resulting in a total of 142 in vivo measurements. A setmore » of two PSDs was fabricated for each patient. At each monitored fraction the PSDs were attached to the anterior surface of an endorectal balloon used to immobilize the patient's prostate during treatment. A CT scan was acquired with a CTon- rails linear accelerator to localize the detectors and to calculate the dose expected to be delivered to the detectors. Each PSD acquired data in 10 second intervals for the duration of the treatment. The deviation between expected and measured cumulative dose was calculated for each detector for each fraction, and averaged over each patient and the patient population as a whole. Results: The average difference between expected dose and measured dose ranged from -3.3% to 3.3% for individual patients, with standard deviations between 5.6% and 7.1% for four of the patients. The average difference for the entire population was -0.4% with a standard deviation of 2.8%. The detectors were well tolerated by the patients and the system did not interrupt the clinical workflow. Conclusion: PSDs perform well as in vivo dosimeters, exhibiting good accuracy and precision. This, combined with the practicability of using such a system, positions the PSD as a strong candidate for clinical in vivo dosimetry in the future. This work supported in part by the National Cancer Institute through an R01 grant (CA120198-01A2) and by the American Legion Auxiliary through the American Auxiliary Fellowship in Cancer Research.« less

Improved dose-volume histogram estimates for radiopharmaceutical therapy by optimizing quantitative SPECT reconstruction parameters

NASA Astrophysics Data System (ADS)

Cheng, Lishui; Hobbs, Robert F.; Segars, Paul W.; Sgouros, George; Frey, Eric C.

2013-06-01

In radiopharmaceutical therapy, an understanding of the dose distribution in normal and target tissues is important for optimizing treatment. Three-dimensional (3D) dosimetry takes into account patient anatomy and the nonuniform uptake of radiopharmaceuticals in tissues. Dose-volume histograms (DVHs) provide a useful summary representation of the 3D dose distribution and have been widely used for external beam treatment planning. Reliable 3D dosimetry requires an accurate 3D radioactivity distribution as the input. However, activity distribution estimates from SPECT are corrupted by noise and partial volume effects (PVEs). In this work, we systematically investigated OS-EM based quantitative SPECT (QSPECT) image reconstruction in terms of its effect on DVHs estimates. A modified 3D NURBS-based Cardiac-Torso (NCAT) phantom that incorporated a non-uniform kidney model and clinically realistic organ activities and biokinetics was used. Projections were generated using a Monte Carlo (MC) simulation; noise effects were studied using 50 noise realizations with clinical count levels. Activity images were reconstructed using QSPECT with compensation for attenuation, scatter and collimator-detector response (CDR). Dose rate distributions were estimated by convolution of the activity image with a voxel S kernel. Cumulative DVHs were calculated from the phantom and QSPECT images and compared both qualitatively and quantitatively. We found that noise, PVEs, and ringing artifacts due to CDR compensation all degraded histogram estimates. Low-pass filtering and early termination of the iterative process were needed to reduce the effects of noise and ringing artifacts on DVHs, but resulted in increased degradations due to PVEs. Large objects with few features, such as the liver, had more accurate histogram estimates and required fewer iterations and more smoothing for optimal results. Smaller objects with fine details, such as the kidneys, required more iterations and less smoothing at early time points post-radiopharmaceutical administration but more smoothing and fewer iterations at later time points when the total organ activity was lower. The results of this study demonstrate the importance of using optimal reconstruction and regularization parameters. Optimal results were obtained with different parameters at each time point, but using a single set of parameters for all time points produced near-optimal dose-volume histograms.

Extrapolating the Acute Behavioral Effects of Toluene from 1-Hour to 24-Hour Exposures in Rats: Roles of Dose Metric, and Metabolic and Behavioral Tolerance.

EPA Science Inventory

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

Clinical Impact of Additional Cytogenetic Aberrations, cKIT and RAS Mutations, and Treatment Elements in Pediatric t(8;21)-AML: Results From an International Retrospective Study by the International Berlin-Frankfurt-Münster Study Group

PubMed Central

Klein, Kim; Kaspers, Gertjan; Harrison, Christine J.; Beverloo, H. Berna; Reedijk, Ardine; Bongers, Mathilda; Cloos, Jacqueline; Pession, Andrea; Reinhardt, Dirk; Zimmerman, Martin; Creutzig, Ursula; Dworzak, Michael; Alonzo, Todd; Johnston, Donna; Hirsch, Betsy; Zapotocky, Michal; De Moerloose, Barbara; Fynn, Alcira; Lee, Vincent; Taga, Takashi; Tawa, Akio; Auvrignon, Anne; Zeller, Bernward; Forestier, Erik; Salgado, Carmen; Balwierz, Walentyna; Popa, Alexander; Rubnitz, Jeffrey; Raimondi, Susana; Gibson, Brenda

2015-01-01

Purpose This retrospective cohort study aimed to determine the predictive relevance of clinical characteristics, additional cytogenetic aberrations, and cKIT and RAS mutations, as well as to evaluate whether specific treatment elements were associated with outcomes in pediatric t(8;21)-positive patients with acute myeloid leukemia (AML). Patients and Methods Karyotypes of 916 pediatric patients with t(8;21)-AML were reviewed for the presence of additional cytogenetic aberrations, and 228 samples were screened for presence of cKIT and RAS mutations. Multivariable regression models were used to assess the relevance of anthracyclines, cytarabine, and etoposide during induction and overall treatment. End points were the probability of achieving complete remission, cumulative incidence of relapse (CIR), probability of event-free survival, and probability of overall survival. Results Of 838 patients included in final analyses, 92% achieved complete remission. The 5-year overall survival, event-free survival, and CIR were 74%, 58%, and 26%, respectively. cKIT mutations and RAS mutations were not significantly associated with outcome. Patients with deletions of chromosome arm 9q [del(9q); n = 104] had a lower probability of complete remission (P = .01). Gain of chromosome 4 (+4; n = 21) was associated with inferior CIR and survival (P < .01). Anthracycline doses greater than 150 mg/m2 and etoposide doses greater than 500 mg/m2 in the first induction course and high-dose cytarabine 3 g/m2 during induction were associated with better outcomes on various end points. Cumulative doses of cytarabine greater than 30 g/m2 and etoposide greater than 1,500 mg/m2 were associated with lower CIR rates and better probability of event-free survival. Conclusion Pediatric patients with t(8;21)-AML and additional del(9q) or additional +4 might not be considered at good risk. Patients with t(8;21)-AML likely benefit from protocols that have high doses of anthracyclines, etoposide, and cytarabine during induction, as well as from protocols comprising cumulative high doses of cytarabine and etoposide. PMID:26573082

Modelling the external radiation exposure from the Chernobyl fallout using data from the Swedish municipality measurement system.

PubMed

Jönsson, Mattias; Tondel, Martin; Isaksson, Mats; Finck, Robert; Wålinder, Robert; Mamour, Afrah; Rääf, Christopher

2017-11-01

In connection with the Chernobyl fallout and the subsequent deposition of radionuclides in Sweden, Swedish municipalities launched a measurement program to monitor the external radiation exposure. This program encompasses measurements of the ambient dose equivalent rate 1 m above ground at selected locations, and repeats those measurements at the same locations at 7-month intervals. Measurement data compiled from the seven locations with the highest deposition were combined with data from aerial surveys since May 1986 of ground deposition of 137 Cs, high-resolution gamma spectrometry performed at four locations in May 1986, and measurements from fixed continuous air gamma rate monitoring stations from 28 April to 15 May 1986. Based on these datasets, a model of the time pattern of the external dose rate in terms of ambient dose equivalent rate from the Chernobyl fallout was developed. The decrease in the ambient dose equivalent rate could, on average, be described by a four-component exponential decay function with effective half-times of 6.8 ± 0.3 d, 104 ± 26 d, 1.0 ± 0.02 y and 5.5 ± 0.09 y, respectively. The predominant contributions to the external dose rate in the first month were from short-lived fission products superseded by 134 Cs and then 137 Cs. Integrated over 70 y and using extrapolation of the curve fits, our model predicts that 137 Cs contributes about 60% and 134 Cs contributes about 30% of the external effective dose at these seven locations. The projected time-integrated 70 y external effective dose to an unshielded person from all nuclides per unit total activity deposition of 137 Cs is estimated to be 0.29 ± 0.0.08 mSv/(kBq m -2 ). These results are in agreement with those found in Chernobyl contaminated Russian forest areas, and emphasize the usefulness of maintaining a long-term and regular measurement program in contaminated areas. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Moureau-Zabotto, Laurence, E-mail: moureaul@ipc.unicancer.fr; Ortholan, Cecile; Hannoun-Levi, Jean-Michel

Purpose: To assess retrospectively the clinical outcome in anal cancer patients, with lymph node involvement, treated with split-course radiation therapy and receiving a boost through external beam radiation therapy (EBRT) or brachytherapy (BCT). Methods and Materials: From 2000 to 2005, among 229 patients with invasive nonmetastatic anal squamous cell carcinoma, a selected group of 99 patients, with lymph node involvement, was studied. Tumor staging reported was T1 in 4 patients, T2 in 16 patients, T3 in 49 patients, T4 in 16 patients, and T unknown in 14 patients and as N1 in 67 patients and N2/N3 in 32 patients. Patientsmore » underwent a first course of EBRT (mean dose, 45.1 Gy) followed by a boost (mean dose, 18 Gy) using EBRT (50 patients) or BCT (49 patients). All characteristics of patients and tumors were well balanced between the BCT and EBRT groups. Prognostic factors of cumulative rate of local recurrence (CRLR), cumulative rate of distant (including nodal) recurrence (CRDR), colostomy-free survival (CFS) rate, and overall survival (OS) rate were analyzed for the overall population and according to the nodal status classification. Results: The median follow-up was 71.5 months. The 5-year CRLR, CRDR, CFS rate, and OS rate were 21%, 19%, 63%, and 74.4%, respectively. In the overall population, the type of node involvement (N1 vs N2/N3) was the unique independent prognostic factor for CRLR. In N1 patients, by use of multivariate analysis, BCT boost was the unique prognostic factor for CRLR (4% for BCT vs 31% for EBRT; hazard ratio, 0.08; P=.042). No studied factors were significantly associated with CRDR, CFS, and OS. No difference with regard to boost technique and any other factor studied was observed in N2/N3 patients for any kind of recurrence. Conclusion: In anal cancer, even in the case of initial perirectal node invasion, BCT boost is superior to EBRT boost for CRLR, without an influence on OS, suggesting that N1 status should not be a contraindication to use of a BCT boost technique, as well as emphasizing the important of investigating the benefit of BCT boost in prospective randomized trials.« less

Effects of a radiation dose reduction strategy for computed tomography in severely injured trauma patients in the emergency department: an observational study.

PubMed

Kim, Soo Hyun; Jung, Seung Eun; Oh, Sang Hoon; Park, Kyu Nam; Youn, Chun Song

2011-11-03

Severely injured trauma patients are exposed to clinically significant radiation doses from computed tomography (CT) imaging in the emergency department. Moreover, this radiation exposure is associated with an increased risk of cancer. The purpose of this study was to determine some effects of a radiation dose reduction strategy for CT in severely injured trauma patients in the emergency department. We implemented the radiation dose reduction strategy in May 2009. A prospective observational study design was used to collect data from patients who met the inclusion criteria during this one year study (intervention group) from May 2009 to April 2010. The prospective data were compared with data collected retrospectively for one year prior to the implementation of the radiation dose reduction strategy (control group). By comparison of the cumulative effective dose and the number of CT examinations in the two groups, we evaluated effects of a radiation dose reduction strategy. All the patients met the institutional adult trauma team activation criteria. The radiation doses calculated by the CT scanner were converted to effective doses by multiplication by a conversion coefficient. A total of 118 patients were included in this study. Among them, 33 were admitted before May 2009 (control group), and 85 were admitted after May 2009 (intervention group). There were no significant differences between the two groups regarding baseline characteristics, such as injury severity and mortality. Additionally, there was no difference between the two groups in the mean number of total CT examinations per patient (4.8 vs. 4.5, respectively; p = 0.227). However, the mean effective dose of the total CT examinations per patient significantly decreased from 78.71 mSv to 29.50 mSv (p < 0.001). The radiation dose reduction strategy for CT in severely injured trauma patients effectively decreased the cumulative effective dose of the total CT examinations in the emergency department. But not effectively decreased the number of CT examinations.

Validation of ELDO approaches for retrospective assessment of cumulative eye lens doses of interventional cardiologists-results from DoReMi project.

PubMed

Domienik, J; Farah, J; Struelens, L

2016-12-01

The first validation results of the two approaches developed in the ELDO project for retrospective assessment of eye lens doses for interventional cardiologists (ICs) are presented in this paper. The first approach (a) is based on both the readings from the routine whole body dosimeter worn above the lead apron and procedure-dependent conversion coefficients, while the second approach (b) is based on detailed information related to the occupational exposure history of the ICs declared in a questionnaire and eye lens dose records obtained from the relevant literature. The latter approach makes use of various published eye lens doses per procedure as well as the appropriate correction factors which account for the use of radiation protective tools designed to protect the eye lens. To validate both methodologies, comprehensive measurements were performed in several Polish clinics among recruited physicians. Two dosimeters measuring whole body and eye lens doses were worn by every physician for at least two months. The estimated cumulative eye lens doses, calculated from both approaches, were then compared against the measured eye lens dose value for every physician separately. Both approaches results in comparable estimates of eye lens doses and tend to overestimate rather than underestimate the eye lens doses. The measured and estimated doses do not differ, on average, by a factor higher than 2.0 in 85% and 62% of the cases used to validate approach (a) and (b), respectively. In specific cases, however, the estimated doses differ from the measured ones by as much as a factor of 2.7 and 5.1 for method (a) and (b), respectively. As such, the two approaches can be considered accurate when retrospectively estimating the eye lens doses for ICs and will be of great benefit for ongoing epidemiological studies.

An automated voxelized dosimetry tool for radionuclide therapy based on serial quantitative SPECT/CT imaging

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

Jackson, Price A.; Kron, Tomas; Beauregard, Jean-Mathieu

2013-11-15

Purpose: To create an accurate map of the distribution of radiation dose deposition in healthy and target tissues during radionuclide therapy.Methods: Serial quantitative SPECT/CT images were acquired at 4, 24, and 72 h for 28 {sup 177}Lu-octreotate peptide receptor radionuclide therapy (PRRT) administrations in 17 patients with advanced neuroendocrine tumors. Deformable image registration was combined with an in-house programming algorithm to interpolate pharmacokinetic uptake and clearance at a voxel level. The resultant cumulated activity image series are comprised of values representing the total number of decays within each voxel's volume. For PRRT, cumulated activity was translated to absorbed dose basedmore » on Monte Carlo-determined voxel S-values at a combination of long and short ranges. These dosimetric image sets were compared for mean radiation absorbed dose to at-risk organs using a conventional MIRD protocol (OLINDA 1.1).Results: Absorbed dose values to solid organs (liver, kidneys, and spleen) were within 10% using both techniques. Dose estimates to marrow were greater using the voxelized protocol, attributed to the software incorporating crossfire effect from nearby tumor volumes.Conclusions: The technique presented offers an efficient, automated tool for PRRT dosimetry based on serial post-therapy imaging. Following retrospective analysis, this method of high-resolution dosimetry may allow physicians to prescribe activity based on required dose to tumor volume or radiation limits to healthy tissue in individual patients.« less

A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa

PubMed Central

Kang, Sang Bum; Marchelletta, Ronald R; Penrose, Harrison; Docherty, Michael J; McCole, Declan F

2015-01-01

Linaclotide, a synthetic guanylyl cyclase C (GC-C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia. GC-C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short-circuit current (Isc). Subsequent Isc responses to the cAMP agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance. Isc responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on TER that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation. PMID:26038704

A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa.

PubMed

Kang, Sang Bum; Marchelletta, Ronald R; Penrose, Harrison; Docherty, Michael J; McCole, Declan F

2015-03-01

Linaclotide, a synthetic guanylyl cyclase C (GC-C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia. GC-C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short-circuit current (I sc). Subsequent I sc responses to the cAMP agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance. I sc responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on TER that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation.

Incidence of cervical human papillomavirus infection in systemic lupus erythematosus women.

PubMed

Mendoza-Pinto, C; García-Carrasco, M; Vallejo-Ruiz, V; Méndez-Martínez, S; Taboada-Cole, A; Etchegaray-Morales, I; Muñóz-Guarneros, M; Reyes-Leyva, J; López-Colombo, A

2017-08-01

Objectives Our objective was to study the incidence, persistence and clearance of human papillomavirus infection in systemic lupus erythematosus women and assess risk factors for persistence of human papillomavirus infection. Methods We carried out a prospective, observational cohort study of 127 systemic lupus erythematosus women. Patients were evaluated at baseline and at three years. Traditional and systemic lupus erythematosus women-related disease risk factors were collected. Gynaecological evaluations and cervical cytology screening were made. Human papillomavirus detection and genotyping were made by polymerase chain reaction and linear array. Results The cumulative prevalence of human papillomavirus infection increased from 22.8% at baseline to 33.8% at three years; p = < 0.001: 20.1% of patients experienced 43 incident infections. The risk of any human papillomavirus infection was 10.1 per 1000 patient-months. At three years, 47 (88.6%) prevalent infections were cleared. Independent risk factors associated with incident human papillomavirus infection included more lifetime sexual partners (odds ratio = 1.8, 95% confidence interval = 1.11-3.0) and cumulative cyclophosphamide dose (odds ratio = 3.9, 95% confidence interval = 1.2-12.8). Conclusions In systemic lupus erythematosus women, the cumulative prevalence of human papillomavirus infection, including high risk-human papillomavirus and multiple human papillomavirus infections, may increase over time. Most persistent infections were low risk-human papillomavirus. The number of lifetime sexual partners and the cumulative cyclophosphamide dose were independently associated with incident human papillomavirus infection.

Cumulative total effective whole-body radiation dose in critically ill patients.

PubMed

Rohner, Deborah J; Bennett, Suzanne; Samaratunga, Chandrasiri; Jewell, Elizabeth S; Smith, Jeffrey P; Gaskill-Shipley, Mary; Lisco, Steven J

2013-11-01

Uncertainty exists about a safe dose limit to minimize radiation-induced cancer. Maximum occupational exposure is 20 mSv/y averaged over 5 years with no more than 50 mSv in any single year. Radiation exposure to the general population is less, but the average dose in the United States has doubled in the past 30 years, largely from medical radiation exposure. We hypothesized that patients in a mixed-use surgical ICU (SICU) approach or exceed this limit and that trauma patients were more likely to exceed 50 mSv because of frequent diagnostic imaging. Patients admitted into 15 predesignated SICU beds in a level I trauma center during a 30-day consecutive period were prospectively observed. Effective dose was determined using Huda's method for all radiography, CT imaging, and fluoroscopic examinations. Univariate and multivariable linear regressions were used to analyze the relationships between observed values and outcomes. Five of 74 patients (6.8%) exceeded exposures of 50 mSv. Univariate analysis showed trauma designation, length of stay, number of CT scans, fluoroscopy minutes, and number of general radiographs were all associated with increased doses, leading to exceeding occupational exposure limits. In a multivariable analysis, only the number of CT scans and fluoroscopy minutes remained significantly associated with increased whole-body radiation dose. Radiation levels frequently exceeded occupational exposure standards. CT imaging contributed the most exposure. Health-care providers must practice efficient stewardship of radiologic imaging in all critically ill and injured patients. Diagnostic benefit must always be weighed against the risk of cumulative radiation dose.

Fenoterol delivery by Respimat soft mist inhaler versus CFC metered dose inhaler: cumulative dose-response study in asthma patients.

PubMed

Vincken, Walter; Dewberry, Helen; Moonen, Diane

2003-09-01

Respimat (RMT) soft mist inhaler (SMI) is a novel, propellant-free alternative to chlorofluorocarbon metered-dose inhalers (CFC-MDIs). The aim of this study was to evaluate the safety and establish the equipotent dose of fenoterol delivered by RMT SMI vs. a conventional MDI. Double-blind, randomized, crossover, comparative study between fenoterol inhaled via RMT (either 50 microg/actuation, RMT50; or 100 microg/actuation. RMT100) and MDI (100 microg/actuation; MDI100). A total of 41 asthma patients received cumulative doses of fenoterol 600 microg (RMT50) or 1200 microg (RMT100 and MDI100) on 3 test days. The bronchodilator response (forced expiratory volume in 1 second [FEV1]) was considered therapeutically equivalent (i.e., noninferior) if the 95% confidence intervals for the difference in their mean changes from baseline were within limits of +/- 0.15L. Systemic exposure was evaluated from plasma fenoterol levels. Adverse events (AEs) were recorded. RMT50 and RMT100 produced noninferior bronchodilatation to MDI100 from 30minutes after the first dose. RMT50 showed equivalent safety and tolerability to MDI100, whereas RMT100 produced a higher incidence of AEs, a significantly greater plasma potassium reduction and a significant increase in pulse rate. Fenoterol plasma levels were twice as high with RMT100 as with RMT50 or MDI100. CONCLUSIONS; The nominal dose of fenoterol administered via RMT SMI can be at least halved to achieve equivalent efficacy, safety, and tolerability to a MDI.

Risk and Protective Factors for Psychological Adjustment among Low-Income, African American Children

ERIC Educational Resources Information Center

Gabalda, Megan K.; Thompson, Martie P.; Kaslow, Nadine J.

2010-01-01

This investigation identifies unique risk and protective factors for internalizing and externalizing problems among 8- to 12-year-old, low-income, African American children and tests cumulative risk and protective models. A total of 152 mother-child dyads complete questionnaires. Receipt of food stamps, mother's distress, and child maltreatment…

Radiation-Induced Cranial Nerve Palsy: A Cross-Sectional Study of Nasopharyngeal Cancer Patients After Definitive Radiotherapy

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

Kong, Lin, E-mail: konglinj@gmail.co; Lu, Jiade J.; Department of Radiation Oncology, National University Cancer Institute of Singapore

2011-04-01

Purpose: To address the characteristics and the causative factors of radiation-induced cranial nerve palsy (CNP) in nasopharyngeal carcinoma (NPC) patients with an extensive period of followed-up. Patients and Methods: A total of 317 consecutive and nonselected patients treated with definitive external-beam radiotherapy between November 1962 and February 1995 participated in this study. The median doses to the nasopharynx and upper neck were 71 Gy (range, 55-86 Gy) and 61 Gy (range, 34-72 Gy), respectively. Conventional fractionation was used in 287 patients (90.5%). Forty-five patients (14.2%) received chemotherapy. Results: The median follow-up was 11.4 years (range, 5.1-38.0 years). Ninety-eight patients (30.9%)more » developed CNP, with a median latent period of 7.6 years (range, 0.3-34 years). Patients had a higher rate of CNP (81 cases, 25.5%) in lower-group cranial nerves compared with upper group (44 cases, 13.9%) ({chi}{sup 2} = 34.444, p < 0.001). Fifty-nine cases experienced CNP in more than one cranial nerve. Twenty-two of 27 cases (68.8%) of intragroup CNP and 11 of 32 cases (40.7%) of intergroup CNP occurred synchronously ({chi}{sup 2} = 4.661, p = 0.031). The cumulative incidences of CNP were 10.4%, 22.4%, 35.5%, and 44.5% at 5, 10, 15, and 20 years, respectively. Multivariate analyses revealed that CNP at diagnosis, chemotherapy, total radiation dose to the nasopharynx, and upper neck fibrosis were independent risk factors for developing radiation-induced CNP. Conclusion: Radiation-induced fibrosis may play an important role in radiation-induced CNP. The incidence of CNP after definitive radiotherapy for NPC remains high after long-term follow-up and is dose and fractionation dependent.« less

Nested Case-control Study of Occupational Radiation Exposure and Breast and Esophagus Cancer Risk among Medical Diagnostic X Ray Workers in Jiangsu of China.

PubMed

Wang, Fu-Ru; Fang, Qiao-Qiao; Tang, Wei-Ming; Xu, Xiao-San; Mahapatra, Tanmay; Mahapatra, Sanchita; Liu, Yu-Fei; Yu, Ning-Le; Sun, Quan-Fu

2015-01-01

Medical diagnostic X-ray workers are one occupational group that expose to the long-term low-dose external radiation over their working lifetime, and they may under risk of different cancers. This study aims to determine the relationship between the occupational X-ray radiation exposure and cancer risk among these workers in Jiangsu, China. We conducted Nested case-control study to investigate the occupational X-ray radiation exposure and cancer risk. Data were collected through self-administered questionnaire, which includes but not limits to demographic data, personal behaviors and family history of cancer. Retrospective dose reconstruction was conducted to estimate the cumulative doses of the x-ray workers. Inferential statistics, t-test and 2 tests were used to compare the differences between each group. We used the logistic regression model to calculate the odds ratio (OR) and 95% confidence interval (CI) of cancer by adjusting the age, gender. All 34 breast cancer cases and 45 esophageal cancer cases that detected in a cohort conducted among health workers between 1950~2011 were included in this presented study, and 158 cancer-free controls were selected by frequency-matched (1:2). Our study found that the occupational radiation exposure was associated with a significantly increased cancer risk compared with the control, especially in breast cancer and esophageal cancer (adjusted OR=2.90, 95% CI: 1.19-7.04 for breast cancer; OR=4.19, 95% CI: 1.87-9.38 for esophageal cancer, and OR=3.43, 95% CI: 1.92-6.12 for total cancer, respectively). The occupational X-ray radiation exposure was associated with increasing cancer risk, which indicates that proper intervention and prevention strategies may be needed in order to bring down the occupational cancer risk.

Efficacy of ipamorelin, a novel ghrelin mimetic, in a rodent model of postoperative ileus.

PubMed

Venkova, Kalina; Mann, William; Nelson, Richard; Greenwood-Van Meerveld, Beverley

2009-06-01

Ghrelin and ghrelin mimetics stimulate appetite and enhance gastric motility. The present study investigates whether ipamorelin, a selective growth hormone secretagogue and agonist of the ghrelin receptor, would accelerate gastrointestinal transit and ameliorate the symptoms in a rodent model of postoperative ileus (POI). Fasted male rats were subjected to laparotomy and intestinal manipulation. At the end of surgery, a dye marker was infused in the proximal colon to evaluate postsurgical colonic transit time, which was the time to the first bowel movement. In addition, fecal pellet output, food intake, and body weight were monitored regularly for 48 h. Ipamorelin (0.01-1 mg/kg), growth hormone-releasing peptide (GHRP)-6 (20 microg/kg), or vehicle (saline) were administered via intravenous bolus infusion after a single dosing or a 2-day repetitive dosing regimen (four doses a day at 3-h intervals). Compared with the vehicle, a single dose of ipamorelin (1 mg/kg) or GHRP-6 (20 microg/kg) decreased the time to the first bowel movement but had no effect on cumulative fecal output, food intake, or body weight gain measured 48 h after the surgery. In contrast, repetitive dosing of ipamorelin (0.1 or 1 mg/kg) significantly increased the cumulative fecal pellet output, food intake, and body weight gain. The results suggest that postsurgical intravenous infusions of ipamorelin may ameliorate the symptoms in patients with POI.

The effect of atypical antipsychotics on pituitary gland volume in patients with first-episode psychosis: a longitudinal MRI study.

PubMed

Nicolo, John-Paul; Berger, Gregor E; Garner, Belinda A; Velakoulis, Dennis; Markulev, Connie; Kerr, Melissa; McGorry, Patrick D; Proffitt, Tina-Marie; McConchie, Mirabel; Pantelis, Christos; Wood, Stephen J

2010-01-01

Pituitary volume is currently measured as a marker of hypothalamic-pituitary-adrenal hyperactivity in patients with psychosis despite suggestions of susceptibility to antipsychotics. Qualifying and quantifying the effect of atypical antipsychotics on the volume of the pituitary gland will determine whether this measure is valid as a future estimate of HPA-axis activation in psychotic populations. To determine the qualitative and quantitative effect of atypical antipsychotic medications on pituitary gland volume in a first-episode psychosis population. Pituitary volume was measured from T1-weighted magnetic resonance images in a group of 43 first-episode psychosis patients, the majority of whom were neuroleptic-naïve, at baseline and after 3months of treatment, to determine whether change in pituitary volume was correlated with cumulative dose of atypical antipsychotic medication. There was no significant baseline difference in pituitary volume between subjects and controls, or between neuroleptic-naïve and neuroleptic-treated subjects. Over the follow-up period there was a negative correlation between percentage change in pituitary volume and cumulative 3-month dose of atypical antipsychotic (r=-0.37), i.e. volume increases were associated with lower doses and volume decreases with higher doses. Atypical antipsychotic medications may reduce pituitary gland volume in a dose-dependent manner suggesting that atypical antipsychotic medication may support affected individuals to cope with stress associated with emerging psychotic disorders.

Assessment of Some Immune Parameters in Occupationally Exposed Nuclear Power Plants Workers

PubMed Central

Panova, Delyana; Djounova, Jana; Rupova, Ivanka; Penkova, Kalina

2015-01-01

The purpose of this article is to analyze the results of a 10-year survey of the radiation effects of some immune parameters of occupationally exposed personnel from the Nuclear Power Plant “Kozloduy”, Bulgaria. 438 persons working in NPP with cumulative doses between 0.06 mSv and 766.36mSv and a control group with 65 persons were studied. Flow cytometry measurements of T, B, natural killer (NK) and natural killer T (NKT) cell lymphocyte populations were performed. Data were interpreted with regard to cumulative doses, length of service and age. The average values of the studied parameters of cellular immunity were in the reference range relative to age and for most of the workers were not significantly different from the control values. Low doses of ionizing radiation showed some trends of change in the number of CD3+CD4+ helper-inducer lymphocytes, CD3+ CD8+ and NKT cell counts. The observed changes in some of the studied parameters could be interpreted in terms of adaptation processes at low doses. At doses above 100–200 mSv, compensatory mechanisms might be involved to balance deviations in lymphocyte subsets. The observed variations in some cases could not be attributed only to the radiation exposure because of the impact of a number of other exogenous and endogenous factors on the immune system. PMID:26675014

EPR TOOTH DOSIMETRY OF SNTS AREA INHABITANTS.

PubMed

Sholom, Sergey; Desrosiers, Marc; Bouville, André; Luckyanov, Nicholas; Chumak, Vadim; Simon, Steven L

2007-07-01

The determination of external dose to teeth of inhabitants of settlements near the Semipalatinsk Nuclear Test Site (SNTS) was conducted using the EPR dosimetry technique to assess radiation doses associated with exposure to radioactive fallout from the test site. In this study, tooth doses have been reconstructed for 103 persons with all studied teeth having been formed before the first nuclear test in 1949. Doses above those received from natural background radiation, termed "accident doses", were found to lie in the range from zero to approximately 2 Gy, with one exception, a dose for one person from Semipalatinsk city was approximately 9 Gy. The variability of reconstructed doses within each of the settlements demonstrated heterogeneity of the deposited fallout as well as variations in lifestyle. The village mean external gamma doses for residents of nine[ settlements were in the range from a few tens of mGy to approximately 100 mGy.

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.

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.

Cumulative effects of antiandrogenic chemical mixtures and their relevance to human health risk assessment.

PubMed

Howdeshell, Kembra L; Hotchkiss, Andrew K; Gray, L Earl

2017-03-01

Toxicological studies of defined chemical mixtures assist human health risk assessment by establishing how chemicals interact with one another to induce an effect. This paper reviews how antiandrogenic chemical mixtures can alter reproductive tract development in rats with a focus on the reproductive toxicant phthalates. The reviewed studies compare observed mixture data to mathematical mixture model predictions based on dose addition or response addition to determine how the individual chemicals in a mixture interact (e.g., additive, greater, or less than additive). Phthalate mixtures were observed to act in a dose additive manner based on the relative potency of the individual phthalates to suppress fetal testosterone production. Similar dose additive effects have been reported for mixtures of phthalates with antiandrogenic pesticides of differing mechanisms of action. Overall, data from these phthalate experiments in rats can be used in conjunction with human biomonitoring data to determine individual hazard indices, and recent cumulative risk assessments in humans indicate an excess risk to antiandrogenic chemical mixtures that include phthalates only or phthalates in combination with other antiandrogenic chemicals. Published by Elsevier GmbH.

10 CFR 835.702 - Individual monitoring records.

Code of Federal Regulations, 2010 CFR

2010-01-01

... emergency exposures. (b) Recording of the non-uniform equivalent dose to the skin is not required if the... internal dose (committed effective dose or committed equivalent dose) is not required for any monitoring...: (i) The effective dose from external sources of radiation (equivalent dose to the whole body may be...

10 CFR 835.702 - Individual monitoring records.

Code of Federal Regulations, 2011 CFR

2011-01-01

... emergency exposures. (b) Recording of the non-uniform equivalent dose to the skin is not required if the... internal dose (committed effective dose or committed equivalent dose) is not required for any monitoring...: (i) The effective dose from external sources of radiation (equivalent dose to the whole body may be...

10 CFR 835.702 - Individual monitoring records.

Code of Federal Regulations, 2014 CFR

2014-01-01

... emergency exposures. (b) Recording of the non-uniform equivalent dose to the skin is not required if the... internal dose (committed effective dose or committed equivalent dose) is not required for any monitoring...: (i) The effective dose from external sources of radiation (equivalent dose to the whole body may be...

10 CFR 835.702 - Individual monitoring records.

Code of Federal Regulations, 2013 CFR

2013-01-01

... emergency exposures. (b) Recording of the non-uniform equivalent dose to the skin is not required if the... internal dose (committed effective dose or committed equivalent dose) is not required for any monitoring...: (i) The effective dose from external sources of radiation (equivalent dose to the whole body may be...

10 CFR 835.702 - Individual monitoring records.

Code of Federal Regulations, 2012 CFR

2012-01-01

... emergency exposures. (b) Recording of the non-uniform equivalent dose to the skin is not required if the... internal dose (committed effective dose or committed equivalent dose) is not required for any monitoring...: (i) The effective dose from external sources of radiation (equivalent dose to the whole body may be...

DEMONSTRATION OF HUMAN EXPOSURE TOOLS

EPA Science Inventory

The Human Exposure and Atmospheric Sciences Division (HEASD) of the National Exposure Research Laboratory (NERL) conducts research on exposure measurements, human activity patterns, exposure and dose models, and cumulative exposures critical for the Agency to make scientificall...

Assessing the overall benefit of a medication: cumulative benefit of secukinumab over time in patients with moderate-to-severe plaque psoriasis.

PubMed

Armstrong, April W; Feldman, Steven R; Korman, Neil J; Meng, Xiangyi; Guana, Adriana; Nyirady, Judit; Herrera, Vivian; Zhao, Yang

2017-05-01

Conventional measurements for assessing psoriasis treatment effects capture improvements at fixed, pre-specified timepoints, failing to account for cumulative clinical benefit over time. Explore the innovative concept of "cumulative clinical benefit" by examining the effect of secukinumab over 52 weeks in moderate-to-severe psoriasis patients. Cumulative clinical benefit was determined as the area-under-the-curve of the percentage of responders over 52 weeks (AUC 0-52 wks ), using pooled data from two phase III trials for patients receiving secukinumab (300 or 150 mg) or etanercept. Normalized cumulative benefit with secukinumab 300 mg, secukinumab 150 mg, and etanercept was 74.2%, 63.2%, and 50.5%, respectively, for PASI 75; 58.0%, 42.5%, and 29.5%, respectively, for PASI 90; 32.3%, 18.8%, and 8.7%, respectively, for PASI 100; and 58.3%, 47.9%, and 38.3%, respectively, for DLQI 0/1. 52-week PASI 75 clinical benefit ratios for secukinumab 300 and 150 mg versus etanercept were 1.47 and 1.25, respectively; the ratio of the two secukinumab doses was 1.17, favoring 300 mg. Post hoc analysis. Cumulative clinical benefit estimated by AUC 0-52 wks is a novel measure for comparing psoriasis treatments. Secukinumab 300 mg provides greater cumulative clinical benefit than secukinumab 150 mg; both provide greater cumulative benefit than etanercept.

Evidence for Dose-Additive Effects of Pyrethroids on Motor Activity in Rats

PubMed Central

Wolansky, Marcelo J.; Gennings, Chris; DeVito, Michael J.; Crofton, Kevin M.

2009-01-01

Background Pyrethroids are neurotoxic insecticides used in a variety of indoor and outdoor applications. Previous research characterized the acute dose–effect functions for 11 pyrethroids administered orally in corn oil (1 mL/kg) based on assessment of motor activity. Objectives We used a mixture of these 11 pyrethroids and the same testing paradigm used in single-compound assays to test the hypothesis that cumulative neurotoxic effects of pyrethroid mixtures can be predicted using the default dose–addition theory. Methods Mixing ratios of the 11 pyrethroids in the tested mixture were based on the ED30 (effective dose that produces a 30% decrease in response) of the individual chemical (i.e., the mixture comprised equipotent amounts of each pyrethroid). The highest concentration of each individual chemical in the mixture was less than the threshold for inducing behavioral effects. Adult male rats received acute oral exposure to corn oil (control) or dilutions of the stock mixture solution. The mixture of 11 pyrethroids was administered either simultaneously (2 hr before testing) or after a sequence based on times of peak effect for the individual chemicals (4, 2, and 1 hr before testing). A threshold additivity model was fit to the single-chemical data to predict the theoretical dose–effect relationship for the mixture under the assumption of dose additivity. Results When subthreshold doses of individual chemicals were combined in the mixtures, we found significant dose-related decreases in motor activity. Further, we found no departure from the predicted dose-additive curve regardless of the mixture dosing protocol used. Conclusion In this article we present the first in vivo evidence on pyrethroid cumulative effects supporting the default assumption of dose addition. PMID:20019907

Epibatidine, an alkaloid from the poison frog Epipedobates tricolor, is a powerful ganglionic depolarizing agent.

PubMed

Fisher, M; Huangfu, D; Shen, T Y; Guyenet, P G

1994-08-01

Epibatidine, a newly discovered alkaloid from the skin of Dendrobatidae frogs, has structural similarities to nicotine. We examined the effects of epibatidine on cardiorespiratory function and ganglionic synaptic transmission. Superior cervical or splanchnic sympathetic nerve discharge (sSND) and phrenic nerve discharge (PND) were recorded along with arterial pressure (AP) in urethane-anesthetized, paralyzed and artificially ventilated rats. Epibatidine administered i.v. at low doses (0.5-2 micrograms/kg) produced a transient increase in AP and sSND, followed by a decrease and return to baseline; this low dose of epibatidine also produced a dose-dependent increase in PND. At high doses (cumulative dose of 8-16 micrograms/kg), epibatidine produced bradycardia, a profound depression in sSND and a transient elimination of PND. After i.v. administration of the ganglionic blocker chlorisondamine (5 mg/kg), AP was still increased by 1 microgram/kg epibatidine (+39 +/- 11 mm Hg). This pressor effect was not altered by pretreatment with the alpha-1 adrenergic antagonist phentolamine (+40 +/- 10 mm Hg); however, it was blocked by additional pretreatment with the vasopressin antagonist [beta-mercapto-beta,beta-cyclopentamethylenepropiony1, O-ET-Tyr2,Val4,Arg8]vasopressin (50 micrograms/kg i.v.; +2 +/- 0.4 mm Hg). Low doses of epibatidine (0.5-2 micrograms/kg) produced firing of postganglionic neurons in a decentralized ganglion preparation and potentiated synaptic transmission; at high doses (cumulative dose of 8-16 micrograms/kg), the alkaloid blocked ganglionic synaptic transmission. These results suggest that epibatidine is a potent agonist of ganglionic nicotinic receptors and that the alkaloid elicits cardiorespiratory effects similar to those of nicotine.

Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

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

Aubuchon, Adam C., E-mail: acaubuchon@gmail.com; Chan, Michael D.; Lovato, James F.

2011-11-15

Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90).more » The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.« less

Maternal Methadone Dose, Placental Methadone Concentrations, and Neonatal Outcomes

PubMed Central

de Castro, Ana; Jones, Hendreé E.; Johnson, Rolley E.; Gray, Teresa R.; Shakleya, Diaa M.; Huestis, Marilyn A.

2015-01-01

BACKGROUND Few investigations have used placenta as an alternative matrix to detect in utero drug exposure, despite its availability at the time of birth and the large amount of sample. Methadone-maintained opioid-dependent pregnant women provide a unique opportunity to examine the placental disposition of methadone and metabolite [2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)], to explore their correlations with maternal methadone dose and neonatal outcomes, and to test the ability to detect in utero exposure to illicit drugs. METHODS We calculated the correlations of placental methadone and EDDP concentrations and their correlations with maternal methadone doses and neonatal outcomes. Cocaine- and opiate-positive placenta results were compared with the results for meconium samples and for urine samples collected throughout gestation. RESULTS Positive correlations were found between placental methadone and EDDP concentrations (r = 0.685), and between methadone concentration and methadone dose at delivery (r = 0.542), mean daily dose (r = 0.554), mean third-trimester dose (r = 0.591), and cumulative daily dose (r = 0.639). The EDDP/methadone concentration ratio was negatively correlated with cumulative daily dose (r = 0.541) and positively correlated with peak neonatal abstinence syndrome (NAS) score (r = 0.513). Placental EDDP concentration was negatively correlated with newborn head circumference (r = 0.579). Cocaine and opiate use was detected in far fewer placenta samples than in thrice-weekly urine and meconium samples, a result suggesting a short detection window for placenta. CONCLUSIONS Quantitative methadone and EDDP measurement may predict NAS severity. The placenta reflects in utero drug exposure for a shorter time than meconium but may be useful when meconium is unavailable or if documentation of recent exposure is needed. PMID:21245372

Importance of a Patient Dosimetry and Clinical Follow-up Program in the Detection of Radiodermatitis After Long Percutaneous Coronary Interventions

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

Vano, Eliseo, E-mail: eliseov@med.ucm.es; Escaned, Javier; Vano-Galvan, Sergio

Complex percutaneous interventions often require high radiation doses likely to produce skin radiation injuries. We assessed the methodology used to select patients with potential skin injuries in cardiac procedures and in need of clinical follow-up. We evaluated peak skin dose and clinical follow-up in a case of radiodermatitis produced during a total occlusion recanalization. This prospective study followed CIRSE and ACC/AHA/SCAI recommendations for patient radiation dose management in interventional procedures carried out in a university hospital with a workload of 4200 interventional cardiac procedures per year. Patient dose reports were automatically transferred to a central database. Patients exceeding trigger levelsmore » for air kerma area product (500 Gy cm{sup 2}) and cumulative skin dose (5 Gy) were counseled and underwent follow-up for early detection of skin injuries, with dermatologic support. The Ethical Committee and the Quality Assurance and Radiation Safety Committee approved the program. During 2010, a total of 13 patients (3.0/1,000 that year) received dose values exceeding trigger levels in the cardiovascular institute. Only one patient, who had undergone two consecutive procedures resulting in 970 Gy cm{sup 2} and 13.0 Gy as cumulative skin dose, showed signs of serious radiodermatitis that resolved in 3.7 months. The remaining patients did not manifest skin lesions during follow-up, and whenever patient examination was not feasible as part of the follow-up, neither patients nor families reported any skin injuries. Peak skin dose calculation and close clinical follow-up were feasible and appropriate, with a moderate additional workload for the staff and satisfaction for the patient.« less

Establishment of the central radiation dose registration system for decontamination work involving radioactive fallout emitted by the Fukushima Daiichi APP accident.

PubMed

Yasui, Shojiro

2016-10-01

With respect to radiation protection for decontamination efforts involving radioactive fallout emitted by the accident at the Fukushima Daiichi Atomic Power Plant, new regulations were established and obligated employers to monitor, record, and store of workers' dose records, and to check their past dose records at the time of employment. However, cumulative doses may not be properly maintained if a worker declares incorrect values for past doses. In response, with facilitation from the Ministry of Health, Labour and Welfare, primary contractors of decontamination works decided to establish a central dose registration system. There are four major issues in the design of the system to be resolved, included the following: primary contractors (a) do not have a legal responsibility to perform dose control for subcontractors, (b) do not have the right to control decontamination sites, (c) often organize joint ventures, and (d) correspond to a wide range of ambient dose rates. To resolve the issues, requirements of the system included the following: (a) centralize the operation of radiation passbooks, which records past doses and the results of medical examinations to each worker; (b) develop a database system that could register all dose data and accept inquiry from primary contractors; (c) establish a permanent data storage system for transferred records; and (d) provide graded type of services that are appropriate to the risk of radiation exposure. The system started its operation in December 2013 and provided dose distributions in April and July 2015. The average yearly dose in 2014 was 0.7 mSv, which increased by 0.2 mSv from 0.5 mSv in 2012 and 2013. However, no cumulative dose from 2012-2014 exceeded 20 mSv, which was far below than the dose limits (100 mSv/5 years and 50 mSv/year). Although current dose distributions of decontamination workers were within appropriate levels, careful monitoring of dose distribution is necessary for preserving the proper implementation of radiation protection prescribed in the regulations.

Safety of coronary CT angiography and functional testing for stable chest pain in the PROMISE trial: A randomized comparison of test complications, incidental findings, and radiation dose.

PubMed

Lu, Michael T; Douglas, Pamela S; Udelson, James E; Adami, Elizabeth; Ghoshhajra, Brian B; Picard, Michael H; Roberts, Rhonda; Lee, Kerry L; Einstein, Andrew J; Mark, Daniel B; Velazquez, Eric J; Carter, William; Ridner, Michael; Al-Khalidi, Hussein R; Hoffmann, Udo

Coronary computed tomography angiography (CTA) and functional testing strategies for stable chest pain yield similar outcomes; one aspect that may guide test choice is safety. We compared test safety (test complications, incidental findings, and effective radiation dose) between CTA and functional testing as-tested in PROMISE (PROspective Multicenter Imaging Study for Evaluation of Chest Pain). In the subgroup whose physicians intended nuclear stress over other functional tests if randomized to the functional arm, we compared radiation dose of CTA versus nuclear stress and identified characteristics associated with dose. Of 9470 patients, none had major and <1% had minor complications (CTA: 0.8% [37/4633] vs. functional: 0.6% [27/4837]). CTA identified more incidental findings (11.6% [539/4633] vs. 0.7% [34/4837], p < 0.001), most commonly pulmonary nodules (9.4%, 437/4633). CTA had similar 90-day cumulative radiation dose to functional testing. However, in the subgroup whose physicians intended nuclear stress (CTA 3147; nuclear 3203), CTA had lower median index test (8.8 vs. 12.6 mSv, p < 0.001) and 90-day cumulative (11.6 vs. 13.1 mSv, p < 0.001) dose, independent of patient characteristics. The lowest nuclear doses employed 1-day Tc-99m protocols (12.2 mSv). The lowest CTA doses were at sites performing ≥500 CTAs/year (6.9 mSv) and with advanced (latest available) CT scanners (5.5 mSv). Complications were negligibly rare for both CTA and functional testing. CTA detects more incidental findings. Compared to nuclear stress testing, CTA's lower radiation dose, independent of patient characteristics, makes it an attractive test choice. Radiation dose varies with imaging protocol, indicating opportunities to further reduce dose. (ClinicalTrials.gov number, NCT01174550). Copyright © 2017 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Cumulative exposure to traumatic events in older adults.

PubMed

Ogle, Christin M; Rubin, David C; Siegler, Ilene C

2014-01-01

The present study examined the impact of cumulative trauma exposure on current posttraumatic stress disorder (PTSD) symptom severity in a nonclinical sample of adults in their 60s. The predictive utility of cumulative trauma exposure was compared to other known predictors of PTSD, including trauma severity, personality traits, social support, and event centrality. Community-dwelling adults (n = 2515) from the crest of the Baby Boom generation completed the Traumatic Life Events Questionnaire, the PTSD Checklist, the NEO Personality Inventory, the Centrality of Event Scale, and rated their current social support. Cumulative trauma exposure predicted greater PTSD symptom severity in hierarchical regression analyses consistent with a dose-response model. Neuroticism and event centrality also emerged as robust predictors of PTSD symptom severity. In contrast, the severity of individuals' single most distressing life event, as measured by self-report ratings of the A1 PTSD diagnostic criterion, did not add explanatory variance to the model. Analyses concerning event categories revealed that cumulative exposure to childhood violence and adulthood physical assaults were most strongly associated with PTSD symptom severity in older adulthood. Moreover, cumulative self-oriented events accounted for a larger percentage of variance in symptom severity compared to events directed at others. Our findings suggest that the cumulative impact of exposure to traumatic events throughout the life course contributes significantly to posttraumatic stress in older adulthood above and beyond other known predictors of PTSD.

The use of ionisation chambers for dose rate measurements at industrial irradiation plants

NASA Astrophysics Data System (ADS)

Sephton, J. P.; Sharpe, P. H. G.; Chu, R. D. H.

2002-03-01

The use of ionisation chambers to measure dose rate at industrial irradiation plants has been studied as part of a wider project on real time dosimetry. The characteristics required of such a chamber are discussed. These include the ability to withstand operation at high cumulative doses (up to 5 MGy) and dose rates of up to about 150 kGy h -1. Other desirable features are water equivalence and immunity to environmental conditions such as temperature, pressure and humidity. A number of chambers have been assessed experimentally and a suitable chamber selected. The dosimetric characteristics of the chosen chamber have been assessed by comparison with absorbed dose measurements made using chemical dosimeters.

Radiation Dose to Post-Chernobyl Cleanup Workers

Cancer.gov

Radiation dose calculation for post-Chernobyl Cleanup Workers in Ukraine - both external radiation exposure due to fallout and internal doses due to inhalation (I131 intake) or ingestion of contaminated foodstuffs.

The Stochastic Human Exposure and Dose Simulation Model for Multimedia, Multipathway Chemicals: Dietary Module Version 1: Technical Manual

EPA Pesticide Factsheets

SHEDS - Multimedia is EPA's premier physically-based, probabilistic model, that can simulate cumulative or aggregate exposures for a population across a variety of multimedia, multipathway environmental chemicals.

Depth distribution of absorbed dose on the external surface of Cosmos 1887 biosatellite

NASA Technical Reports Server (NTRS)

Watts, J. W., Jr.; Parnell, T. A.; Akatov, Yu. A.; Dudkin, V. E.; Kovalev, E. E.; Benton, E. V.; Frank, A. L.

1995-01-01

Significant absorbed dose levels exceeding 1.0 Gy day(exp -1) have been measured on the external surface of the Cosmos 1887 biosatellite as functions of depth in stacks of thin thermoluminescent detectors (TLD's) made in U.S.S.R. and U.S.A. The dose was found to decrease rapidly with increasing absorber thickness, thereby indicating the presence of intensive fluxes of low-energy particles. Comparison between the U.S.S.R. and U.S.A. results and calculations based on the Vette Model environment are in satisfactory agreement. The major contribution to the dose under thin shielding thickness is shown to be from electrons. The fraction of the dose due to protons and heavier charged particles increases with shielding thickness.

Depth distribution of absorbed dose on the external surface of Cosmos 1887 biosatellite

NASA Technical Reports Server (NTRS)

Dudkin, V. E.; Kovalev, E. E.; Benton, E. V.; Frank, A. L.; Watts, J. W. Jr; Parnell, T. A.

1990-01-01

Significant absorbed dose levels exceeding 1.0 Gy day-1 have been measured on the external surface of the Cosmos 1887 biosatellite as functions of depth in stacks of thin thermoluminescent detectors (TLDs) of U.S.S.R. and U.S.A. manufacture. The dose was found to decrease rapidly with increasing absorber thickness, thereby indicating the presence of intensive fluxes of low-energy particles. Comparison between the U.S.S.R. and U.S.A. results and calculations based on the Vette Model environment are in satisfactory agreement. The major contribution to the dose under thin shielding thickness is shown to be from electrons. The fraction of the dose due to protons and heavier charged particles increases with shielding thickness.

LDR vs. HDR brachytherapy for localized prostate cancer: the view from radiobiological models.

PubMed

King, Christopher R

2002-01-01

Permanent LDR brachytherapy and temporary HDR brachytherapy are competitive techniques for clinically localized prostate radiotherapy. Although a randomized trial will likely never be conducted comparing these two forms of brachytherapy, a comparative radiobiological modeling analysis proves useful in understanding some of their intrinsic differences, several of which could be exploited to improve outcomes. Radiobiological models based upon the linear quadratic equations are presented for fractionated external beam, fractionated (192)Ir HDR brachytherapy, and (125)I and (103)Pd LDR brachytherapy. These models incorporate the dose heterogeneities present in brachytherapy based upon patient-derived dose volume histograms (DVH) as well as tumor doubling times and repair kinetics. Radiobiological parameters are normalized to correspond to three accepted clinical risk factors based upon T-stage, PSA, and Gleason score to compare models with clinical series. Tumor control probabilities (TCP) for LDR and HDR brachytherapy (as monotherapy or combined with external beam) are compared with clinical bNED survival rates. Predictions are made for dose escalation with HDR brachytherapy regimens. Model predictions for dose escalation with external beam agree with clinical data and validate the models and their underlying assumptions. Both LDR and HDR brachytherapy achieve superior tumor control when compared with external beam at conventional doses (<70 Gy), but similar to results from dose escalation series. LDR brachytherapy as boost achieves superior tumor control than when used as monotherapy. Stage for stage, both LDR and current HDR regimens achieve similar tumor control rates, in agreement with current clinical data. HDR monotherapy with large-dose fraction sizes might achieve superior tumor control compared with LDR, especially if prostate cancer possesses a high sensitivity to dose fractionation (i.e., if the alpha/beta ratio is low). Radiobiological models support the current clinical evidence for equivalent outcomes in localized prostate cancer with either LDR or HDR brachytherapy using current dose regimens. However, HDR brachytherapy dose escalation regimens might be able to achieve higher biologically effective doses of irradiation in comparison to LDR, and hence improved outcomes. This advantage over LDR would be amplified should prostate cancer possess a high sensitivity to dose fractionation (i.e., a low alpha/beta ratio) as the current evidence suggests.

Mandibular Inferior Cortical Bone Thickness on Panoramic Radiographs in Patients using Bisphosphonates

PubMed Central

Torres, Sandra R.; Chen, Curtis S. K.; Leroux, Brian G.; Lee, Peggy P.; Hollender, Lars G.; Lloid, Michelle; Drew, Shane Patrick; Schubert, Mark M.

2015-01-01

Objective To detect dimensional changes in the mandibular cortical bone associated with bisphosphonate (BP) use and to correlate the measurements of the cortical bone with the cumulative dose of BP therapy. Methods Mandibular inferior cortical bone thickness (MICBT) was measured under the mental foramen from panoramic radiographs of subjects using BP with and without bisphosphonate related osteonecrosis of the jaws (BRONJ) and controls. Results The highest mean MICBT was observed in BRONJ subjects 6.81 (± 1.35 mm), when compared to subjects using BP 5.44 (± 1.09 mm) and controls 4.79 (± 0.85 mm; p<0.01). The mean MICBT of BRONJ subjects was significantly higher than that of subjects using BP without BRONJ. There was a correlation between MICBT and cumulative dose of zolendronate. Conclusion The MICBT on panoramic radiograph is a potentially useful tool for the detection of dimensional changes associated with BP therapy. PMID:25864820

Radioactivity concentrations in soils in the Qingdao area, China.

PubMed

Qu, Limei; Yao, De; Cong, Pifu; Xia, Ning

2008-10-01

The specific activity concentrations of radionuclides (238)U, (232)Th, and (40)K of 2300 sampling points in the Qingdao area were measured by an FD-3022 gamma-ray spectrometer. The radioactivity concentrations of (238)U, (232)Th, and (40)K ranged from 3.3 to 185.3, from 6.9 to 157.2, and from 115.8 to 7834.4 Bq kg(-1), respectively. The air-absorbed dose at 1 meter above ground, effective annual dose, external hazard index, and radium equivalent activity were also calculated to systematically evaluate the radiological hazards of the natural radioactivity in Qingdao. The air-absorbed dose, effective annual dose, external hazard index, and radium equivalent activity in the study area were 98.6 nGy h(-1), 0.12 mSv, 0.56, 197 Bq kg(-1), respectively. Compared with the worldwide value, the air-absorbed dose is slightly high, but the other factors are all lower than the recommended value. The natural external exposure will not pose significant radiological threat to the population. In conclusion, the Qingdao area is safe with regard to the radiological level and suitable for living.

EPR TOOTH DOSIMETRY OF SNTS AREA INHABITANTS

PubMed Central

Sholom, Sergey; Desrosiers, Marc; Bouville, André; Luckyanov, Nicholas; Chumak, Vadim

2009-01-01

The determination of external dose to teeth of inhabitants of settlements near the Semipalatinsk Nuclear Test Site (SNTS) was conducted using the EPR dosimetry technique to assess radiation doses associated with exposure to radioactive fallout from the test site. In this study, tooth doses have been reconstructed for 103 persons with all studied teeth having been formed before the first nuclear test in 1949. Doses above those received from natural background radiation, termed “accident doses”, were found to lie in the range from zero to approximately 2 Gy, with one exception, a dose for one person from Semipalatinsk city was approximately 9 Gy. The variability of reconstructed doses within each of the settlements demonstrated heterogeneity of the deposited fallout as well as variations in lifestyle. The village mean external gamma doses for residents of nine[ settlements were in the range from a few tens of mGy to approximately 100 mGy. PMID:19590746

Time Course and Accumulated Risk of Severe Urinary Adverse Events After High- Versus Low-Dose-Rate Prostate Brachytherapy With or Without External Beam Radiation Therapy

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

Tward, Jonathan D., E-mail: Jonathan.Tward@hci.utah.edu; Jarosek, Stephanie; Chu, Haitao

Purpose: Severe urinary adverse events (UAEs) include surgical treatment of urethral stricture, urinary incontinence, and radiation cystitis. We compared the incidence of grade 3 UAEs, according to the Common Terminology Criteria for Adverse Events, after low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy, as well as after LDR plus external beam radiation therapy (EBRT) and HDR plus EBRT. Methods and Materials: Men aged >65 years with nonmetastatic prostate cancer were identified from the Surveillance, Epidemiology, and End Results–Medicare database who were treated with LDR (n=12,801), HDR (n=685), LDR plus EBRT (n=8518), or HDR plus EBRT (n=2392). The populations were balanced by propensity weighting, andmore » the Kaplan-Meier incidence of severe UAEs was compared. Propensity-weighted Cox proportional hazards models were used to compare the adjusted hazard of UAEs. These UAEs were compared with those in a cohort of men not treated for prostate cancer. Results: Median follow-up was 4.3 years. At 8 years, the propensity-weighted cumulative UAE incidence was highest after HDR plus EBRT (26.6% [95% confidence interval, 23.8%-29.7%]) and lowest after LDR (15.7% [95% confidence interval, 14.8%-16.6%]). The absolute excess risk over nontreated controls at 8 years was 1.9%, 3.8%, 8.4%, and 12.9% for LDR, HDR, LDR plus EBRT, and HDR plus EBRT, respectively. These represent numbers needed to harm of 53, 26, 12, and 8 persons, respectively. The additional risk of development of a UAE related to treatment for LDR, LDR plus EBRT, and HDR plus EBRT was greatest within the 2 years after treatment and then continued to decline over time. Beyond 4 years, the risk of development of a new severe UAE matched the baseline risk of the control population for all treatments. Conclusions: Toxicity differences were observed between LDR and HDR, but the differences did not meet statistical significance. However, combination radiation therapy (either HDR plus EBRT or LDR plus EBRT) increases the risk of severe UAEs compared with HDR alone or LDR alone. The highest increased risk of urinary toxicity occurs within the 2 years after therapy and then declines to an approximately 1% increase in incidence per year.« less

Time Course and Accumulated Risk of Severe Urinary Adverse Events After High- Versus Low-Dose-Rate Prostate Brachytherapy With or Without External Beam Radiation Therapy.

PubMed

Tward, Jonathan D; Jarosek, Stephanie; Chu, Haitao; Thorpe, Cameron; Shrieve, Dennis C; Elliott, Sean

2016-08-01

Severe urinary adverse events (UAEs) include surgical treatment of urethral stricture, urinary incontinence, and radiation cystitis. We compared the incidence of grade 3 UAEs, according to the Common Terminology Criteria for Adverse Events, after low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy, as well as after LDR plus external beam radiation therapy (EBRT) and HDR plus EBRT. Men aged >65 years with nonmetastatic prostate cancer were identified from the Surveillance, Epidemiology, and End Results-Medicare database who were treated with LDR (n=12,801), HDR (n=685), LDR plus EBRT (n=8518), or HDR plus EBRT (n=2392). The populations were balanced by propensity weighting, and the Kaplan-Meier incidence of severe UAEs was compared. Propensity-weighted Cox proportional hazards models were used to compare the adjusted hazard of UAEs. These UAEs were compared with those in a cohort of men not treated for prostate cancer. Median follow-up was 4.3 years. At 8 years, the propensity-weighted cumulative UAE incidence was highest after HDR plus EBRT (26.6% [95% confidence interval, 23.8%-29.7%]) and lowest after LDR (15.7% [95% confidence interval, 14.8%-16.6%]). The absolute excess risk over nontreated controls at 8 years was 1.9%, 3.8%, 8.4%, and 12.9% for LDR, HDR, LDR plus EBRT, and HDR plus EBRT, respectively. These represent numbers needed to harm of 53, 26, 12, and 8 persons, respectively. The additional risk of development of a UAE related to treatment for LDR, LDR plus EBRT, and HDR plus EBRT was greatest within the 2 years after treatment and then continued to decline over time. Beyond 4 years, the risk of development of a new severe UAE matched the baseline risk of the control population for all treatments. Toxicity differences were observed between LDR and HDR, but the differences did not meet statistical significance. However, combination radiation therapy (either HDR plus EBRT or LDR plus EBRT) increases the risk of severe UAEs compared with HDR alone or LDR alone. The highest increased risk of urinary toxicity occurs within the 2 years after therapy and then declines to an approximately 1% increase in incidence per year. Copyright © 2016. Published by Elsevier Inc.

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

EPA Science Inventory

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

Cumulative stress in research animals: Telomere attrition as a biomarker in a welfare context?

PubMed

Bateson, Melissa

2016-02-01

Progress in improving animal welfare is currently limited by the lack of objective methods for assessing lifetime experience. I propose that telomere attrition, a cellular biomarker of biological age, provides a molecular measure of cumulative experience that could be used to assess the welfare impact of husbandry regimes and/or experimental procedures on non-human animals. I review evidence from humans that telomere attrition is accelerated by negative experiences in a cumulative and dose-dependent manner, but that this attrition can be mitigated or even reversed by positive life-style interventions. Evidence from non-human animals suggests that despite some specific differences in telomere biology, stress-induced telomere attrition is a robust phenomenon, occurring in a range of species including mice and chickens. I conclude that telomere attrition apparently integrates positive and negative experience in an accessible common currency that translates readily to novel species--the Holy Grail of a cumulative welfare indicator. © 2015 The Author. BioEssays published by WILEY Periodicals, Inc.

Negative impact of high cumulative glucocorticoid dose on bone metabolism of patients with myasthenia gravis.

PubMed

Braz, Nayara Felicidade Tomaz; Rocha, Natalia Pessoa; Vieira, Érica Leandro Marciano; Gomez, Rodrigo Santiago; Barbosa, Izabela Guimarães; Malheiro, Olívio Brito; Kakehasi, Adriana Maria; Teixeira, Antonio Lucio

2017-08-01

This current study aimed to evaluate the frequency of low bone mass, osteopenia, and osteoporosis in patients with myasthenia gravis (MG) and to investigate the possible association between bone mineral density (BMD) and plasma levels of bone metabolism markers. Eighty patients with MG and 62 controls BMD were measured in the right femoral neck and lumbar spine by dual-energy X-ray absorptiometry. Plasma concentrations of osteocalcin, osteopontin, osteoprotegerin, tumor necrosis factor (TNF-α), interleukin (IL)-1β, IL-6, dickkopf (DKK-1), sclerostin, insulin, leptin, adrenocorticotropic hormone, parathyroid hormone, and fibroblast growth factor (FGF-23) were analyzed by Luminex®. The mean age of patients was 41.9 years, with 13.5 years of length of illness, and a mean cumulative dose of glucocorticoids 38,123 mg. Patients had significant reduction in BMD of the lumbar, the femoral neck, and in the whole body when compared with controls. Fourteen percent MG patients had osteoporosis at the lumbar spine and 2.5% at the femoral neck. In comparison with controls, patients with MG presented lower levels of osteocalcin, adrenocorticotropic hormone, parathyroid hormone, sclerostin, TNF-α, and DKK-1 and higher levels of FGF-23, leptin, and IL-6. There was a significant negative correlation between cumulative glucocorticoid dose and serum calcium, lumbar spine T-score, femoral neck BMD, T-score, and Z-score. After multivariate analysis, higher TNF-α levels increased the likelihood of presenting low bone mass by 2.62. MG patients under corticotherapy presented low BMD and altered levels of bone markers.

Integration of kerma-area product and cumulative air kerma determination into a skin dose tracking system for fluoroscopic imaging procedures

NASA Astrophysics Data System (ADS)

Vijayan, Sarath; Shankar, Alok; Rudin, Stephen; Bednarek, Daniel R.

2016-03-01

The skin dose tracking system (DTS) that we developed provides a color-coded mapping of the cumulative skin dose distribution on a 3D graphic of the patient during fluoroscopic procedures in real time. The DTS has now been modified to also calculate the kerma area product (KAP) and cumulative air kerma (CAK) for fluoroscopic interventions using data obtained in real-time from the digital bus on a Toshiba Infinix system. KAP is the integral of air kerma over the beam area and is typically measured with a large-area transmission ionization chamber incorporated into the collimator assembly. In this software, KAP is automatically determined for each x-ray pulse as the product of the air kerma/ mAs from a calibration file for the given kVp and beam filtration times the mAs per pulse times the length and width of the beam times a field nonuniformity correction factor. Field nonuniformity is primarily the result of the heel effect and the correction factor was determined from the beam profile measured using radio-chromic film. Dividing the KAP by the beam area at the interventional reference point provides the area averaged CAK. The KAP and CAK per x-ray pulse are summed after each pulse to obtain the total procedure values in real-time. The calculated KAP and CAK were compared to the values displayed by the fluoroscopy machine with excellent agreement. The DTS now is able to automatically calculate both KAP and CAK without the need for measurement by an add-on transmission ionization chamber.

Issues in the reconstruction of environmental doses on the basis of thermoluminescence measurements in the Techa riverside

NASA Technical Reports Server (NTRS)

Bougrov, N. G.; Goksu, H. Y.; Haskell, E.; Degteva, M. O.; Meckbach, R.; Jacob, P.; Neta, P. I. (Principal Investigator)

1998-01-01

The potential of thermoluminescence measurements of bricks from the contaminated area of the Techa river valley, Southern Urals, Russia, for reconstructing external exposures of affected population groups has been studied. Thermoluminescence dating of background samples was used to evaluate the age of old buildings available on the river banks. The anthropogenic gamma dose accrued in exposed samples is determined by subtracting the natural radiation background dose for the corresponding age from the accumulated dose measured by thermoluminescence. For a site in the upper Techa river region, where the levels of external exposures were extremely high, the depth-dose distribution in bricks and the dependence of accidental dose on the height of the sampling position were determined. For the same site, Monte Carlo simulations of radiation transport were performed for different source configurations corresponding to the situation before and after the construction of a reservoir on the river and evacuation of the population in 1956. A comparison of the results provides an understanding of the features of the measured depth-dose distributions and height dependencies in terms of the source configurations and shows that bricks from the higher sampling positions are likely to have accrued a larger fraction of anthropogenic dose from the time before the construction of the reservoir. The applicability of the thermoluminescent dosimetry method to environmental dose reconstruction in the middle Techa region, where the external exposure was relatively low, was also investigated.

Respirators, internal dose, and Oyster Creek

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

Michal, R.

1996-06-01

This article looks at the experience of Oyster Creek in relaxing the requirements for the use of respirators in all facets of plant maintenance, on the overall dose received by plant maintenance personnel. For Roger Shaw, director of radiological controls for three years at GPU Nuclear Corporation`s Oyster Creek nuclear plant the correct dose balance is determined on a job-by-job basis: Does the job require a respirator, which is an effective means of decreasing worker inhalation of airborne radioactive particles? Will wearing a respirator slow down a worker, consequently increasing whole body radiation exposure by prolonging the time spent inmore » fields of high external radiation? How does respiratory protection affect worker safety and to what degree? While changes to the Nuclear Regulatory Commission`s 10CFR20 have updated the radiation protection requirements for the nuclear industry, certain of the revisions have been directed specifically at reducing worker dose, Shaw said. {open_quotes}It basically delineates that dose is dose,{close_quotes} Shaw said, {open_quotes}regardless of whether it is acquired externally or internally.{close_quotes} The revision of Part 20 changed the industry`s attitude toward internal dose, which had always been viewed negatively. {open_quotes}Internal dose was always seen as preventable by wearing respirators and by using engineering techniques such as ventilation control and decontamination,{close_quotes} Shaw said, {open_quotes}whereas external dose, although reduced where practical, was seen as a fact of the job.{close_quotes}« less

Albumin treatment regimen for type 1 hepatorenal syndrome: a dose-response meta-analysis.

PubMed

Salerno, Francesco; Navickis, Roberta J; Wilkes, Mahlon M

2015-11-25

Recommended treatment for type 1 hepatorenal syndrome consists of albumin and vasoconstrictor. The optimal albumin dose remains poorly characterized. This meta-analysis aimed to determine the impact of albumin dose on treatment outcomes. Clinical studies of type 1 hepatorenal syndrome treatment with albumin and vasoconstrictor were sought. Search terms included: hepatorenal syndrome; albumin; vasoconstrictor; terlipressin; midodrine; octreotide; noradrenaline; and norepinephrine. A meta-analysis was performed of hepatorenal syndrome reversal and survival in relation to albumin dose. Nineteen clinical studies with 574 total patients were included, comprising 8 randomized controlled trials, 8 prospective studies and 3 retrospective studies. The pooled percentage of patients achieving hepatorenal syndrome reversal was 49.5% (95% confidence interval, 40.0-59.1%). Increments of 100 g in cumulative albumin dose were accompanied by significantly increased survival (hazard ratio, 1.15; 95% confidence interval, 1.02-1.31; p = 0.023). A non-significant increase of similar magnitude in hepatorenal syndrome reversal was also observed (odds ratio, 1.15; 95% confidence interval, 0.97-1.37; p = 0.10). Expected survival rates at 30 days among patients receiving cumulative albumin doses of 200, 400 and 600 g were 43.2% (95% confidence interval, 36.4-51.3%), 51.4% (95% confidence interval, 46.3-57.1%) and 59.0% (95% confidence interval, 51.9-67.2), respectively. Neither survival nor hepatorenal syndrome reversal was significantly affected by vasoconstrictor dose or type, treatment duration, age, baseline serum creatinine, bilirubin or albumin, baseline mean arterial pressure, or study design, size or time period. This meta-analysis suggests a dose-response relationship between infused albumin and survival in patients with type 1 hepatorenal syndrome. The meta-analysis provides the best current evidence on the potential role of albumin dose selection in improving outcomes of treatment for type 1 HRS and furnishes guidance for the design of future dose-ranging studies.

Somatotype, the risk of hydroxychloroquine retinopathy, and safe daily dosing guidelines.

PubMed

Browning, David J; Lee, Chong

2018-01-01

The aim of this study was to determine whether somatotype influences the risk of hydroxychloroquine (HC) retinopathy (HCR) and whether dosing by real body weight (RBW), ideal body weight (IBW), or the lesser of these better predicts the risk of HCR. A total of 565 patients taking HC for whom height and weight were recorded and a sensitive ancillary testing modality was used including 10-2 visual fields, spectral domain optical coherence tomography, fundus autofluorescence imaging, and multifocal electroretinography were enrolled. Body mass index (BMI) was compared for patients without and with HCR. Logistic regression models of age, cumulative dose, and daily dosing based on RBW, IBW, or lesser of these were compared. Area under the curve (AUC) of receiver operating characteristic plots was used to assess the diagnostic accuracy of RBW, IBW, and lesser of these guidelines for safe dosing. Probability plots for the risk of retinopathy versus BMI were compared for the different recommended guidelines on safe dosing. A total of 41 patients had HCR. The median BMI was 27.6 (interquartile range [IQR] 24.3, 32.6) and 24.0 (IQR 21.0, 31.6) for patients without and with HCR ( P =0.0102), respectively. AUC for univariate receiver operating characteristic plots of retinopathy versus dosing by RBW, IBW, and lesser of these was 0.71, 0.72, and 0.76, respectively. AUC for multivariate receiver operating characteristic plots of retinopathy versus models incorporating gender, age, cumulative dose, and BMI and differing by including dosing by RBW, IBW, and lesser of these was 0.82, 0.82, and 0.83, respectively. For all of the multivariate logistic models, the risk of retinopathy was higher for lower BMIs. Short, asthenic women are at higher risk for HCR. The 2011 American Academy of Ophthalmology (AAO) guidelines are safer for short, obese women. The 2016 AAO guidelines are safer for short, asthenic patients. Choosing daily dosing based on the lesser of the RBW and IBW guidelines is safer for all patients.

Phase I study of Carzelesin (U-80,244) given (4-weekly) by intravenous bolus schedule

PubMed Central

Awada, A; Punt, C J A; Piccart, M J; Tellingen, O Van; Manen, L Van; Kerger, J; Groot, Y; Wanders, J; Verweij, J; Wagener, D J Th

1999-01-01

Carzelesin is a cyclopropylpyrroloindole analogue which acts as a DNA-sequence-specific alkylating agent. In this phase I study, Carzelesin was given as a 4-weekly 10 min IV infusion to 51 patients with advanced solid tumours. Patients received a median of two courses (range 1–5) at one of nine dose levels: 24, 48, 96, 130, 150, 170, 210, 250 and 300 μg m−2. According to NCI-CTC criteria, non-haematological toxicities (grade 1/2) included fever, nausea and vomiting, mucositis and anorexia, none of which was clearly dose related. The dose-limiting toxicity was haematological and consisted mainly of neutropenia and to a lesser extent thrombocytopenia. From the dose level 150 μg m−2, the haematological toxicity (particularly thrombocytopenia) was delayed in onset, prolonged and cumulative in some patients. In several courses, double WBC nadirs occurred. The maximum tolerated dose for a single course was 300 μg m−2. From the dose level 170 μg m−2, the intended dose intensity could not be delivered to most patients receiving > 2 courses owing to cumulative haematological toxicity. The dose level with the best dose intensity for multiple courses was 150 μg m−2. The pharmacokinetics of Carzelesin and its metabolites (U-76,073; U-76,074) have been established in 31 patients during the first course of treatment using a HPLC method. Carzelesin exhibited linear pharmacokinetics. The concentration of U-76,074 (active metabolite) extended above the lower limit of quantitation (1 ng ml−1) for short periods of time and only at the higher dose levels. There was no relationship between neutropenia and the AUC of the prodrug Carzelesin, but the presence of detectable plasma levels of the active metabolite U-76,074 was usually associated with a substantial decrease in ANC values. © 1999 Cancer Research Campaign PMID:10188890

Increase in fluoroscopic radiation dose in successive sessions of multistage Onyx embolization of brain arteriovenous malformations compared with the first session.

PubMed

Sheen, Jae Jon; Jiang, Yuan Yuan; Kim, Young Eun; Maeng, Jun Young; Kim, Tae-Il; Lee, Deok Hee

2018-03-23

Onyx embolization is a treatment for brain arteriovenous malformations (AVMs). However, multistage embolization usually involves the presence of radiodense Onyx cast from the previous sessions, which may influence the fluoroscopic radiation dose. We compared the fluoroscopic dose between the initial and final embolization sessions. From January 2014 to September 2016, 18 patients underwent multistage Onyx embolization (more than twice) for brain AVMs. The total fluoroscopic duration (minutes), dose-area product (DAP, Gy×cm 2 ), and cumulative air kerma (CAK, mGy) of both the frontal and lateral planes were obtained. We compared the frontal and lateral fluoroscopic dose rates (dose/time) of the final embolization session with those of the initial session. The relationship between the injected Onyx volume and radiation dose was tested. The initial and final procedures on the frontal plane showed significantly different fluoroscopic dose rates (DAP: initial 0.668 Gy×cm 2 /min, final 0.848 Gy×cm 2 /min, P=0.02; CAK: initial 12.7 mGy/min, final 23.1 mGy/min, P=0.007). Those on the lateral plane also showed a similar pattern (DAP: initial 0.365 Gy×cm 2 /min, final 0.519 Gy×cm 2 /min, P=0.03; CAK: initial 6.2 mGy/min, final 12.9 mGy/min, P=0.01). The correlation between the cumulative Onyx volume (vials) and radiation dose ratio of both planes showed an increasing trend (rho 0.4325-0.7053; P=0.0011-0.0730). Owing to the automatic exposure control function during fluoroscopy, successive Onyx embolization procedures increase the fluoroscopic radiation dose in multistage brain AVM embolization because of the presence of radiodense Onyx mass. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Low dose radiation risks for women surviving the a-bombs in Japan: generalized additive model.

PubMed

Dropkin, Greg

2016-11-24

Analyses of cancer mortality and incidence in Japanese A-bomb survivors have been used to estimate radiation risks, which are generally higher for women. Relative Risk (RR) is usually modelled as a linear function of dose. Extrapolation from data including high doses predicts small risks at low doses. Generalized Additive Models (GAMs) are flexible methods for modelling non-linear behaviour. GAMs are applied to cancer incidence in female low dose subcohorts, using anonymous public data for the 1958 - 1998 Life Span Study, to test for linearity, explore interactions, adjust for the skewed dose distribution, examine significance below 100 mGy, and estimate risks at 10 mGy. For all solid cancer incidence, RR estimated from 0 - 100 mGy and 0 - 20 mGy subcohorts is significantly raised. The response tapers above 150 mGy. At low doses, RR increases with age-at-exposure and decreases with time-since-exposure, the preferred covariate. Using the empirical cumulative distribution of dose improves model fit, and capacity to detect non-linear responses. RR is elevated over wide ranges of covariate values. Results are stable under simulation, or when removing exceptional data cells, or adjusting neutron RBE. Estimates of Excess RR at 10 mGy using the cumulative dose distribution are 10 - 45 times higher than extrapolations from a linear model fitted to the full cohort. Below 100 mGy, quasipoisson models find significant effects for all solid, squamous, uterus, corpus, and thyroid cancers, and for respiratory cancers when age-at-exposure > 35 yrs. Results for the thyroid are compatible with studies of children treated for tinea capitis, and Chernobyl survivors. Results for the uterus are compatible with studies of UK nuclear workers and the Techa River cohort. Non-linear models find large, significant cancer risks for Japanese women exposed to low dose radiation from the atomic bombings. The risks should be reflected in protection standards.

TH-AB-207A-03: Skin Dose to Patients Receiving Multiple CTA and CT Exams of the Head

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

Nawfel, RD; Young, G

Purpose: To measure patient skin dose from CT angiography (CTA) and CT exams of the head, and determine if patients having multiple exams could receive cumulative doses that approach or exceed deterministic thresholds. Methods: This study was HIPAA compliant and conducted with IRB approval. Patient skin doses were measured over a 4 month period using nanoDot OSL dosimeters placed on the head of 52 patients for two CT scanners. On each scanner, 26 patients received CT exams (scanner 1: 10 females, 16 males, mean age 64.2 years; scanner 2: 18 females, 8 males, mean age 61.2 years). CT exam dosemore » metrics, CTDIvol and dose-length product (DLP) were recorded for each exam. Additionally, skin dose was measured on an acrylic skull phantom in each scanner and on a neuro-interventional imaging system using clinical protocols. Measured dose data was used to estimate peak skin dose (PSD) for 4 patients receiving multiple exams including CTA, head CT, and cerebral angiography. Results: For scanner 1, the mean PSD for CTA exams (98.9 ± 5.3 mGy) and for routine head CT exams (39.2 ± 3.7 mGy) agreed reasonably well with the PSD measured on the phantom, 105.4 mGy and 40.0 mGy, respectively. Similarly for scanner 2, the mean PSD for CTA exams (98.8 ± 7.4 mGy) and for routine head CT exams (42.9 ± 9.4 mGy) compared well with phantom measurements, 95.2 mGy and 37.6 mGy, respectively. In addition, the mean PSD was comparable between scanners for corresponding patient exams, CTA and routine head CT respectively. PSD estimates ranged from 1.9 – 4.5 Gy among 4 patients receiving multiple exams. Conclusion: Patients having several exams including both CTA and routine head CT may receive cumulative doses approaching or exceeding the threshold for single dose deterministic effects.« less

SU-F-P-27: The Study of Actual DVH for Target and OARs During the Radiotherapy of Non-Small Cell Lung Cancer

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

Ma, C; Yin, Y

2016-06-15

Purpose: To analyze the changes of the volume and dosimetry of target and organs at risk (OARs) by comparing the daily CBCT images and planning CT images of the patients with Non-Small Cell Lung Cancer (NSCLC) and analyze the difference between planned dose and accumulated dose. Methods: This study retrospectively analyzed eight cases of non-small cell lung cancer patients who accepted CRT or IMRT treatment and KV-CBCT. For each patient, the prescription dose was 60Gy and the fraction dose was 2Gy. Deform the daily CBCT images to planning CT images by the mapping of registration to compare the planning dosemore » with cumulative dose of targets and organs at risk in RayStation. Results: The average volume of GTV of 8 patients with CBCT was 88.26% of the original volume. The average plan dose of GTV was 64.49±2.40Gy. The accumulated dose of GTV was 60.13±2.70Gy (P≤0.05). The average volume of PTV to reach the prescription dose was 95.59% for original plan and 81.47% for accumulated plan (P≤0.05). The volume changes of the left and right lung of the original volume was 88.95% and 80.32%, respectively. The average dose of the left and right lung of original plan was 9.31±1.75Gy and 4.33±1.10Gy, respectively(P≥0.05). The average accumulated dose was 9.63±1.96Gy and 4.63±1.36Gy, respectively(P≥0.05). The average plan dose and accumulated dose of heart was 6.88±1.70Gy and 6.38±0.91Gy, respectively (P≥0.05). The average plan maximum dose and accumulated dose for spinal cord was 24.62±5.91Gy and 26.00±5.14Gy, respectively (P≥0.05). Conclusion: The changes of target anatomical structure with NSCLC make difference between the planned dose and cumulative dose. With the dose deformation method, the dose gap can be found between planning dose and delivery dose.« less

Radiation dose to technologists per nuclear medicine examination and estimation of annual dose.

PubMed

Bayram, Tuncay; Yilmaz, A Hakan; Demir, Mustafa; Sonmez, Bircan

2011-03-01

Conventional diagnostic nuclear medicine applications have been continuously increasing in most nuclear medicine departments in Turkey, but to our knowledge no one has studied the doses to technologists who perform nuclear medicine procedures. Most nuclear medicine laboratories do not have separate control rooms for technologists, who are quite close to the patient during data acquisition. Technologists must therefore stay behind lead shields while performing their task if they are to reduce the radiation dose received. The aim of this study was to determine external radiation doses to technologists during nuclear medicine procedures with and without a lead shield. Another aim was to investigate the occupational annual external radiation doses to Turkish technologists. This study used a Geiger-Müller detector to measure dose rates to technologists at various distances from patients (0.25, 0.50, 1, and 2 m and behind a lead shield) and determined the average time spent by technologists at these distances. Deep-dose equivalents to technologists were obtained. The following conventional nuclear medicine procedures were considered: thyroid scintigraphy performed using (99m)Tc pertechnetate, whole-body bone scanning performed using (99m)Tc-methylene diphosphonate, myocardial perfusion scanning performed using (99m)Tc-methoxyisobutyl isonitrile, and (201)Tl (thallous chloride) and renal scanning performed using (99m)Tc-dimercaptosuccinic acid. The measured deep-dose equivalent to technologists per procedure was within the range of 0.13 ± 0.05 to 0.43 ± 0.17 μSv using a lead shield and 0.21 ± 0.07 to 1.01 ± 0.46 μSv without a lead shield. Also, the annual individual dose to a technologist performing only a particular scintigraphic procedure throughout a year was estimated. For a total of 95 clinical cases (71 patients), effective external radiation doses to technologists were found to be within the permissible levels. This study showed that a 2-mm lead shield markedly reduced the external dose to technologists. The doses to technologists varied significantly for different diagnostic applications. Consequently, the estimated annual dose to a technologist performing only a particular scintigraphic procedure is very different from one type of procedure to another. The results of this study should help in determining the rotation time of technologists in different procedures and differences in their individual techniques.

The Stochastic Human Exposure and Dose Simulation Model for Multimedia, Multipathway Chemicals: Residential Module Version 4: User Guide, June 2012

EPA Pesticide Factsheets

SHEDS - Multimedia is EPA's premier physically-based, probabilistic model, that can simulate cumulative or aggregate exposures for a population across a variety of multimedia, multipathway environmental chemicals.

The Stochastic Human Exposure and Dose Simulation Model for Multimedia, Multipathway Chemicals: Residential Module Version 4: Technical Manual, May 2012

EPA Pesticide Factsheets

SHEDS - Multimedia is EPA's premier physically-based, probabilistic model, that can simulate cumulative or aggregate exposures for a population across a variety of multimedia, multipathway environmental chemicals.

The Stochastic Human Exposure and Dose Simulation Model for Multimedia, Multipathway Chemicals: Dietary Module Version 1: User Guide, June 2012

EPA Pesticide Factsheets

SHEDS - Multimedia is EPA's premier physically-based, probabilistic model, that can simulate cumulative or aggregate exposures for a population across a variety of multimedia, multipathway environmental chemicals.

Cardiovascular disease after treatment for Hodgkin's lymphoma: an analysis of nine collaborative EORTC-LYSA trials.

PubMed

Maraldo, Maja V; Giusti, Francesco; Vogelius, Ivan R; Lundemann, Michael; van der Kaaij, Marleen A E; Ramadan, Safaa; Meulemans, Bart; Henry-Amar, Michel; Aleman, Berthe M P; Raemaekers, John; Meijnders, Paul; Moser, Elisabeth C; Kluin-Nelemans, Hanneke C; Feugier, Pierre; Casasnovas, Olivier; Fortpied, Catherine; Specht, Lena

2015-11-01

Cardiovascular disease after treatment is an important concern in cancer survivors. However, knowledge of cardiotoxicity is limited by the retrospective nature of data, which often does not contain details of treatment exposure. To facilitate individual risk counselling of patients, we aimed to quantify the effect of anthracyclines, vinca-alkaloids, and radiotherapy on the risk of cardiovascular disease in patients treated for Hodgkin's lymphoma. In 2009-10, a Life Situation Questionnaire (LSQ) was distributed to patients by mail to assess late-onset effects of Hodgkin's lymphoma treatment in patients who were included in nine successive European Organisation for Research and Treatment of Cancer (EORTC) and the Groupe d'Etude des Lymphomes de l'Adulte (GELA, now renamed LYSA) randomised trials between 1964 and 2004. We reconstructed the mean radiation doses to the heart and carotid arteries and the cumulative doses of anthracyclines and vinca-alkaloids for all patients. Incidence of cardiovascular disease was reported during follow-up and updated through the LSQ. We applied Cox proportional hazards regression analyses to quantify the effect of chemotherapy and radiation on the risk of a first cardiovascular disease event. Information of primary treatment was complete for 6039 patients (median age at diagnosis 30 years [IQR 23-40]; median length of follow-up 9 years [6-14]). 1919 patients responded to the LSQ. 1238 first cardiovascular events were recorded in 703 patients, most were ischaemic heart disease (132 [19%]), congestive heart failure (85 [12%]), arrhythmia (110 [16%]), and valvular disease (77 [11%]). The mean heart radiation dose per 1 Gy increase (HR 1·015 [95% CI 1·006-1·024], p=0·0014) and the dose of anthracyclines per 50 mg/m(2) increase in cumulative dose (1·077 [1·021-1·137], p=0·0064) were significant predictors of cardiovascular disease. Cumulative dose of vinblastine (unadjusted model p=0·77), vincristine (p=0·36), and mean radiation dose to the left (p=0·41) or right (p=0·70) internal carotid artery did not predict for cardiovascular events. Quantification of the increased cardiovascular risk with specific doses of radiation and anthracycline exposure will enable a quantitative assessment of the optimum combination of systemic therapy and radiation, which will help clinicians to balance the risks and benefits of different regimens for individual patients. Rigshospitalet Research Committee, the EORTC Cancer Research Fund, and the Sally Snowman Survivorship Fellowship. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synergistic effect of cumulative corticosteroid dose and immunosuppressants on avascular necrosis in patients with systemic lupus erythematosus.

PubMed

Kwon, H H; Bang, S Y; Won, S; Park, Y; Yi, J H; Joo, Y B; Lee, H S; Bae, S C

2018-01-01

Objectives Avascular necrosis (AVN) is one of the most common causes of organ damage in patients with systemic lupus erythematosus (SLE) and often causes serious physical disability. The aims of this study were to investigate clinical risk factors associated with symptomatic AVN and to analyze their synergistic effects in a large SLE cohort in Korea. Methods Patients with SLE were enrolled and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort, and damage was measured annually according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). AVN was confirmed by imaging study if patients had symptoms. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) were calculated to measure interactions between significant variables. Results Among 1219 SLE patients, symptomatic AVN was the most common type of musculoskeletal damage (10.8%, n = 132). SLE patients with AVN showed an earlier onset age, demonstrated AVN more commonly in conjunction with certain other clinical manifestations such as renal and neuropsychiatric disorders, and received significantly higher total cumulative corticosteroid dose and immunosuppressive agents than did patients without AVN. However, in multivariable analysis, only two variables including use of a cumulative corticosteroid dose greater than 20 g (odds ratio (OR) 3.62, p = 0.015) and use of immunosuppressants including cyclophosphamide or mycophenolate mofetil (OR 4.51, p < 0.001) remained as significant risk factors for AVN. Patients with cumulative corticosteroid dose > 20 g and immunosuppressant use had a 15.44-fold increased risk for AVN, compared with patients without these risk factors ( p < 0.001). RERI, AP and S, which define the strength of interactions between two risk factors, were 9.01 (95% confidence interval (CI) 1.30-16.73), 0.58 (95% CI 0.36-0.81) and 2.66 (95% CI 1.42-4.99), respectively, supporting the presence of synergistic interactions in the development of symptomatic AVN in our Korean lupus cohort. Conclusions An individual risk assessment for AVN development should be made prior to and during treatment for SLE, especially in patients with high-dose corticosteroid and immunosuppressant use regardless of clinical manifestations and disease activity.

Teratogenic effects of external egg applications of methyl mercury in the mallard, Anas platyrhynchos

USGS Publications Warehouse

Hoffman, D.J.; Moore, Johnnie N.

1979-01-01

The embryotoxic potential of external applications of methyl mercury on mallard eggs was investigated to assess the possible impact of mercury transferred from the plumage of effluent-contaminated aquatic birds to their eggs. Eggs were treated on day 3 of development with microliter applications of methyl mercury that was dissolved with ethyl acetate into an aliphatic hydrocarbon vehicle. Mercury analysis by atomic absorption indicated that almost half of the mercury applied entered the eggs past the shell membranes within several days of treatment. Most mortality occurred within this period at doses of 9 microgram of mercury per egg or higher. Decreased embryonic growth resulted with similar doses. A significant incidence of malformations occurred at a dose of 1 microgram per egg. These malformations were mainly minor skeletal aberrations and incomplete ossification. With higher doses of mercury, defects included gross external ones such as micromella, gastroschisis, and eye and brain defects. Application of the aliphatic hydrocarbon vehicle did not result in any of these defects.

The effects of nandrolone decanoate on nutritional parameters in hemodialysis patients.

PubMed

Barton Pai, A; Chretien, C; Lau, A H

2002-07-01

Malnutrition with hypoalbuminemia is an independent predictor of mortality in end-stage renal disease patients. Anabolic steroids reduce protein catabolism and therefore may improve nutritional parameters. This study was undertaken to determine the effects of the anabolic steroid nandrolone decanoate on the nutritional status of hemodialysis patients. Secondary endpoints were to examine the effects of androgen therapy on hematocrit and erythropoietin (EPO) dose. Medical records of chronic hemodialysis patients who received nandrolone decanoate for greater than 30 days were reviewed. Data collected included: demographics, dose, frequency, duration of treatment and cumulative dose of nandrolone. Baseline albumin, transferrin, dry weight, phosphorus, creatinine, hematocrit and erythropoietin dose were obtained for comparison with values after treatment. Of the 9 patients evaluated (mean +/- SD: age 55+/-28 years, 4/9 male), 2 patients received nandrolone doses of 25 mg intramuscularly (i.m.) every week, while the remaining 7 patients received 100 mg i.m. every 2 weeks. The mean +/- SD duration of treatment was 96+/-43 days, with a mean +/- SD cumulative dose of 656+/-371 mg. The mean +/- SD baseline albumin was 2.9+/-0.6 mg/dl which increased to 3.3+/-0.4 mg/dl after treatment (p = 0.045). Dry weight increased from a mean +/- SD of 64.4+/-11.7 kg to 66.0+/-10.9 kg after nandrolone therapy (p = 0.028). Mean +/- SD hematocrit at baseline was 28.2+/-4.5% and increased to 33.2+/-5.1% (p = 0.033). The dose of EPO was reduced in 4 patients (44%) during nandrolone therapy. Nandrolone significantly improved markers of nutritional status in our hemodialysis patients. This therapy may also enhance the hematopoietic effects of EPO.

Occupational radiation procedures and doses in South Korean dentists.

PubMed

Kim, Yoon-Ji; Cha, Eun Shil; Lee, Won Jin

2016-10-01

Dentistry is among the occupations involving chronic exposure to ionizing radiation. Although several cohort studies on medical radiation workers have been conducted in some countries, only a few epidemiological studies on dentists have been performed to examine occupational radiation exposure worldwide. The aim of this study was to investigate occupational characteristics and radiation exposures in South Korean dentists. A total of 658 dentists were surveyed from April 2012 to May 2013, and survey data were linked with dosimetry data from the National Dose Registry. Multiple linear regression analysis was used to identify the relationship between demographic or occupational factors and individual radiation doses. Of the dentists sampled, 78% were men, 51% were younger than age 40, and 61% began employment after 2000. The most frequent procedures performed by dentists were panoramic radiography, followed by intraoral and portable dental radiography. Male dentists were more frequently involved in radiation procedures, and a higher proportion of male than female dentists wore a lead apron for diagnostic radiology. The average annual effective dose was 0.18 mSv for male and 0.13 mSv for female dentists. Female dentists working in provincial areas had significantly higher average annual and cumulative effective doses than those in metropolitan areas. The cumulative effective doses were significantly greater for older dentists, those who entered the field in the 1990s, and those with longer employment duration. Our findings provided detailed information on work practices, number of procedures performed on a weekly basis, and occupational radiation doses, which enabled in-depth evaluation of occupational radiation exposure and work status among dentists. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Shielding design of the Mayo Clinic Scottsdale cyclotron vault

NASA Astrophysics Data System (ADS)

Riper, Kenneth A. Van; Metzger, Robert L.; Nelson, Kevin

2017-09-01

Mayo Clinic Scottsdale (Scottsdale, Arizona) is building a cyclotron vault containing a cyclotron with adjacent targets and a beam line leading to an external target. The targets are irradiated by high energy (15 to 16.5 MeV) protons for the production of radioisotopes. We performed Monte Carlo radiation transport simulations to calculate the radiation dose outside of the vault during irradiation of the cyclotron and external targets. We present the Monte Carlo model including the geometry, sources, and variance reduction methods. Mesh tallies surrounding the vault show the external dose rate is within acceptable limits.

Democratization and life expectancy in Europe, 1960-2008.

PubMed

Mackenbach, Johan P; Hu, Yannan; Looman, Caspar W N

2013-09-01

Over the past five decades, two successive waves of political reform have brought democracy to, first, Spain, Portugal and Greece, and, more recently, Central and Eastern European countries. We assessed whether democratization was associated with improvements in population health, as indicated by life expectancy and cause-specific mortality rates. Data on life expectancy at birth, age-standardized total and cause-specific mortality rates, levels of democracy and potential time-variant confounding variables were collected from harmonized international databanks. In two pooled cross-sectional time-series analyses with country-fixed effects, life expectancy and cause-specific mortality were regressed on measures of current and cumulative democracy, controlling for confounders. A first analysis covered the 1960-1990 period, a second covered the 1987-2008 period. In the 1960-1990 period, current democracy was more strongly associated with higher life expectancy than cumulative democracy. The positive effects of current democracy on total mortality were mediated mainly by lower mortality from heart disease, pneumonia, liver cirrhosis, and suicide. In the 1987-2008 period, however, current democracy was associated with lower, and cumulative democracy with higher life expectancy, particularly among men. The positive effects of cumulative democracy on total mortality were mediated mainly by lower mortality from circulatory diseases, cancer of the breast, and external causes. Current democracy was associated with higher mortality from motor vehicle accidents in both periods, and also with higher mortality from cancer and all external causes in the second. Our results suggest that in Europe during these two periods democratization has had mixed effects. That short-term changes in levels of democracy had positive effects in the first but not in the second period is probably due to the fact that democratization in Central and Eastern Europe was part of a complete system change which caused major societal disruptions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Predictive model of early mortality following acute inhalation of PuO/sub 2/ aerosols. [Extrapolation of beagle data to man

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

Raabe, O.G.; Goldman, M.

Since data on the pulmonary toxicity of plutonium in people are not available, estimates must be based upon available experimental animal data. For this purpose, inhalation studies with beagle dogs exposed to aerosols of /sup 238/PuO/sub 2/ and /sup 239/PuO/sub 2/ were analyzed and a simple model has been proposed to describe apparent dose-response relationships. It was found that for each aerosol and radionuclide form, the cumulative absorbed lung dose that leads to death from lung damage up to 1000 days could be assumed to have a log-normal distribution of values that was independent of time to death. The datamore » was satisfactorily fit to a model in which the time of death postexposure is given by: t = (K/D), with the time to death, the cumulative dose to lung tissue (the killing dose), and anti D the average dose rate to lung tissue from time of exposure to death. The ratios of median K values, normalized to the value for /sup 90/Sr--Y FAP, indicate a relative biological effectiveness (RBE) of 14 for /sup 239/PuO/sub 2/ particles and 5 for /sup 238/PuO/sub 2/ particles. This demonstrates an effect of particle specific activity on relative biological effectiveness for early mortality, since an increase in specific activity of particles leads to a lower apparent RBE.« less

Dosimetric calculations for uranium miners for epidemiological studies.

PubMed

Marsh, J W; Blanchardon, E; Gregoratto, D; Hofmann, W; Karcher, K; Nosske, D; Tomásek, L

2012-05-01

Epidemiological studies on uranium miners are being carried out to quantify the risk of cancer based on organ dose calculations. Mathematical models have been applied to calculate the annual absorbed doses to regions of the lung, red bone marrow, liver, kidney and stomach for each individual miner arising from exposure to radon gas, radon progeny and long-lived radionuclides (LLR) present in the uranium ore dust and to external gamma radiation. The methodology and dosimetric models used to calculate these organ doses are described and the resulting doses for unit exposure to each source (radon gas, radon progeny and LLR) are presented. The results of dosimetric calculations for a typical German miner are also given. For this miner, the absorbed dose to the central regions of the lung is dominated by the dose arising from exposure to radon progeny, whereas the absorbed dose to the red bone marrow is dominated by the external gamma dose. The uncertainties in the absorbed dose to regions of the lung arising from unit exposure to radon progeny are also discussed. These dose estimates are being used in epidemiological studies of cancer in uranium miners.

Paclitaxel-loaded polymeric microparticles: Quantitative relationships between in vitro drug release rate and in vivo pharmacodynamics

PubMed Central

Tsai, Max; Lu, Ze; Wientjes, M. Guillaume; Au, Jessie L.-S.

2013-01-01

Intraperitoneal therapy (IP) has demonstrated survival advantages in patients with peritoneal cancers, but has not become a widely practiced standard-of-care in part due to local toxicity and sub-optimal drug delivery. Paclitaxel-loaded, polymeric microparticles were developed to overcome these limitations. The present study evaluated the effects of microparticle properties on paclitaxel release (extent and rate) and in vivo pharmacodynamics. In vitro paclitaxel release from microparticles with varying physical characteristics (i.e., particle size, copolymer viscosity and composition) was evaluated. A method was developed to simulate the dosing rate and cumulative dose released in the peritoneal cavity based on the in vitro release data. The relationship between the simulated drug delivery and treatment outcomes of seven microparticle compositions was studied in mice bearing IP human pancreatic tumors, and compared to that of the intravenous Cremophor micellar paclitaxel solution used off-label in previous IP studies. Paclitaxel release from polymeric microparticles in vitro was multi-phasic; release was greater and more rapid from microparticles with lower polymer viscosities and smaller diameters (e.g., viscosity of 0.17 vs. 0.67 dl/g and diameter of 5–6 vs. 50–60 μm). The simulated drug release in the peritoneal cavity linearly correlated with treatment efficacy in mice (r2>0.8, p<0.001). The smaller microparticles, which distribute more evenly in the peritoneal cavity compared to the large microparticles, showed greater dose efficiency. For single treatment, the microparticles demonstrated up to 2-times longer survival extension and 4-times higher dose efficiency, relative to the paclitaxel/Cremophor micellar solution. Upon repeated dosing, the paclitaxel/Cremophor micellar solution showed cumulative toxicity whereas the microparticle that yielded 2-times longer survival did not display cumulative toxicity. The efficacy of IP therapy depended on both temporal and spatial factors that were determined by the characteristics of the drug delivery system. A combination of fast- and slow-releasing microparticles with 5–6 μm diameter provided favorable spatial distribution and optimal drug release for IP therapy. PMID:24056144

Early biomarkers of doxorubicin-induced heart injury in a mouse model

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

Desai, Varsha G., E-mail: varsha.desai@fda.hhs.gov; Kwekel, Joshua C.; Vijay, Vikrant

Cardiac troponins, which are used as myocardial injury markers, are released in plasma only after tissue damage has occurred. Therefore, there is a need for identification of biomarkers of earlier events in cardiac injury to limit the extent of damage. To accomplish this, expression profiling of 1179 unique microRNAs (miRNAs) was performed in a chronic cardiotoxicity mouse model developed in our laboratory. Male B6C3F{sub 1} mice were injected intravenously with 3 mg/kg doxorubicin (DOX; an anti-cancer drug), or saline once a week for 2, 3, 4, 6, and 8 weeks, resulting in cumulative DOX doses of 6, 9, 12, 18,more » and 24 mg/kg, respectively. Mice were euthanized a week after the last dose. Cardiac injury was evidenced in mice exposed to 18 mg/kg and higher cumulative DOX dose whereas examination of hearts by light microscopy revealed cardiac lesions at 24 mg/kg DOX. Also, 24 miRNAs were differentially expressed in mouse hearts, with the expression of 1, 1, 2, 8, and 21 miRNAs altered at 6, 9, 12, 18, and 24 mg/kg DOX, respectively. A pro-apoptotic miR-34a was the only miRNA that was up-regulated at all cumulative DOX doses and showed a significant dose-related response. Up-regulation of miR-34a at 6 mg/kg DOX may suggest apoptosis as an early molecular change in the hearts of DOX-treated mice. At 12 mg/kg DOX, up-regulation of miR-34a was associated with down-regulation of hypertrophy-related miR-150; changes observed before cardiac injury. These findings may lead to the development of biomarkers of earlier events in DOX-induced cardiotoxicity that occur before the release of cardiac troponins. - Highlights: • Upregulation of miR-34a before doxorubicin-induced cardiac tissue injury • Apoptosis might be an early event in mouse heart during doxorubicin treatment. • Expression of miR-150 declined before doxorubicin-induced cardiac tissue injury.« less

A prospective case control comparison of the ZeroGravity system versus a standard lead apron as radiation protection strategy in neuroendovascular procedures.

PubMed

Haussen, Diogo C; Van Der Bom, Imramsjah Martijn John; Nogueira, Raul G

2016-10-01

We aimed to compare the performance of the ZeroGravity (ZG) system (radiation protection system composed by a suspended lead suit) against the use of standard protection (lead apron (LA), thyroid shield, lead eyeglasses, table skirts, and ceiling suspended shield) in neuroangiography procedures. Radiation exposure data were prospectively collected in consecutive neuroendovascular procedures between December 2014 and February 2015. Operator No 1 was assigned to the use of an LA (plus lead glasses, thyroid shield, and a 1 mm hanging shield at the groin) while operator No 2 utilized the ZG system. Dosimeters were used to measure peak skin dose for the head, thyroid, and left foot. The two operators performed a total of 122 procedures during the study period. The ZG operator was more commonly the primary operator compared with the LA operator (85% vs 71%; p=0.04). The mean anterior-posterior (AP), lateral, and cumulative dose area product (DAP) radiation exposure as well as the mean fluoroscopy time were not statistically different between the operators' cases. The peak skin dose to the head of the operator with LA was 2.1 times higher (3380 vs 1600 μSv), while the thyroid was 13.9 (4460 vs 320 μSv), the mediastinum infinitely (520 vs 0 μSv), and the foot 3.3 times higher (4870 vs 1470 μSv) compared with the ZG operator, leading to an overall accumulated dose 4 times higher. The ratio of cumulative operator received dose/total cumulative DAP was 2.5 higher on the LA operator. The ZG radiation protection system leads to substantially lower radiation exposure to the operator in neurointerventional procedures. However, substantial exposure may still occur at the level of the lens and thyroid to justify additional protection. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Cumulative exposure to traumatic events in older adults

PubMed Central

Ogle, Christin M.; Rubin, David C.; Siegler, Ilene C.

2014-01-01

Objectives The present study examined the impact of cumulative trauma exposure on current posttraumatic stress disorder (PTSD) symptom severity in a nonclinical sample of adults in their 60s. The predictive utility of cumulative trauma exposure was compared to other known predictors of PTSD, including trauma severity, personality traits, social support, and event centrality. Method Community-dwelling adults (n = 2,515) from the crest of the Baby Boom generation completed the Traumatic Life Events Questionnaire, the PTSD Checklist, the NEO Personality Inventory, the Centrality of Event Scale, and rated their current social support. Results Cumulative trauma exposure predicted greater PTSD symptom severity in hierarchical regression analyses consistent with a dose-response model. Neuroticism and event centrality also emerged as robust predictors of PTSD symptom severity. In contrast, the severity of individuals’ single most distressing life event, as measured by self-report ratings of the A1 PTSD diagnostic criterion, did not add explanatory variance to the model. Analyses concerning event categories revealed that cumulative exposure to childhood violence and adulthood physical assaults were most strongly associated with PTSD symptom severity in older adulthood. Moreover, cumulative self-oriented events accounted for a larger percentage of variance in symptom severity compared to events directed at others. Conclusion Our findings suggest that the cumulative impact of exposure to traumatic events throughout the life course contributes significantly to post-traumatic stress in older adulthood above and beyond other known predictors of PTSD. PMID:24011223

Organ dose conversion coefficients based on a voxel mouse model and MCNP code for external photon irradiation.

PubMed

Zhang, Xiaomin; Xie, Xiangdong; Cheng, Jie; Ning, Jing; Yuan, Yong; Pan, Jie; Yang, Guoshan

2012-01-01

A set of conversion coefficients from kerma free-in-air to the organ absorbed dose for external photon beams from 10 keV to 10 MeV are presented based on a newly developed voxel mouse model, for the purpose of radiation effect evaluation. The voxel mouse model was developed from colour images of successive cryosections of a normal nude male mouse, in which 14 organs or tissues were segmented manually and filled with different colours, while each colour was tagged by a specific ID number for implementation of mouse model in Monte Carlo N-particle code (MCNP). Monte Carlo simulation with MCNP was carried out to obtain organ dose conversion coefficients for 22 external monoenergetic photon beams between 10 keV and 10 MeV under five different irradiation geometries conditions (left lateral, right lateral, dorsal-ventral, ventral-dorsal, and isotropic). Organ dose conversion coefficients were presented in tables and compared with the published data based on a rat model to investigate the effect of body size and weight on the organ dose. The calculated and comparison results show that the organ dose conversion coefficients varying the photon energy exhibits similar trend for most organs except for the bone and skin, and the organ dose is sensitive to body size and weight at a photon energy approximately <0.1 MeV.

Somatic mutation frequencies in the stamen hairs of Tradescantia grown in soil samples from the Bikini Island.

PubMed

Ichikawa, S; Ishii, C

1991-02-01

Somatic pink mutation frequencies in the stamen hairs of Tradescantia BNL 02 clone grown for 76 days in two soil samples taken from the Bikini Island (where a hydrogen bomb explosion test had been conducted in 1954) were investigated. A significantly high mutation frequency (2.58 +/- 0.17 pink mutant events per 10(3) hairs or 1.34 +/- 0.09 pink mutant events per 10(4) hair-cell divisions) was observed for the plant grown in one of the two Bikini soil samples, as compared to the control plants (1.70 +/- 0.14 or 0.88 +/- 0.07, respectively) grown in the field soil of Saitama University. The soil sample which caused the significant increase in mutation frequency contained 6,880 +/- 330 mBq/g 137Cs, 62.5 +/- 4.4 mBq/g 60Co, and some other nuclides; a 150 microR/hr exposure rate being measured on the surface of the soil sample. The effective cumulative external exposures measured for the inflorescences of the plant grown in this soil sample averaged at most 60.8 mR, being too small to explain the significant elevation in mutation frequency observed. On the other hand, internal exposure due to uptake of radioactive nuclides was estimated to be 125 mrad (1.25 mGy) as an accumulated effective dose, mainly based on a gamma-spectrometrical analysis. However, it seemed highly likely that this value of internal exposure was a considerable underestimate, and the internal exposure was considered to be more significant than the external exposure.

The Stochastic Human Exposure and Dose Simulation Model for Multimedia, Multipathway Chemicals: Dietary Module Version 1: Quick Start Guide, May 2012

EPA Pesticide Factsheets

SHEDS - Multimedia is EPA's premier physically-based, probabilistic model, that can simulate cumulative or aggregate exposures for a population across a variety of multimedia, multipathway environmental chemicals.

The Stochastic Human Exposure and Dose Simulation Model for Multimedia, Multipathway Chemicals: Residential Module Version 4: Quick Start Guide, April 2012

EPA Pesticide Factsheets

SHEDS - Multimedia is EPA's premier physically-based, probabilistic model, that can simulate cumulative or aggregate exposures for a population across a variety of multimedia, multipathway environmental chemicals.

A 1-year trial of repeated high-dose intravenous iron isomaltoside 1000 to maintain stable hemoglobin levels in inflammatory bowel disease

PubMed Central

Reinisch, Walter; Altorjay, Istvan; Zsigmond, Ferenc; Primas, Christian; Vogelsang, Harald; Novacek, Gottfried; Reinisch, Sieglinde; Thomsen, Lars L.

2015-01-01

Abstract Objective. Iron isomaltoside 1000 (Monofer®) is a high-dose intravenous (IV) iron, which in a recent 8 weeks trial in inflammatory bowel disease (IBD) subjects with iron deficiency anemia (IDA) demonstrated good tolerability and efficacy. The present trial is an extension to this trial, which evaluates the need for additional high IV iron doses to maintain a stable hemoglobin (Hb) ≥12.0 g/dl. Material and methods. This was a prospective, open-label, 12 months trial of European IBD subjects willing to participate after completing the lead-in trial. Subjects were allowed re-dosing with 500–2000 mg single doses of iron isomaltoside 1000 infused over ∼15 min at 3 months intervals depending on a predefined algorithm. Outcome measures included Hb, safety parameters and need for additional iron dosing. Results. A total of 39 subjects were enrolled of which 34 subjects required re-dosing with a median cumulative 1-year dose of 1.8 g (mean cumulative dose 2.2 g). The mean (SD) Hb was 12.3 (1.5) g/dl at baseline, 12.8 (1.6) g/dl at 3 months, 12.8 (1.6) g/dl at 6 months, 12.9 (1.4) g/dl at 9 months and 12.9 (1.6) g/dl at 12 months. Seventy-four percent of subjects who had an Hb ≥12.0 g/dl at baseline were able to maintain Hb ≥12.0 g/dl till the end of the trial at 12 months. Nonserious probably related hypersensitivity reactions without significant hypotension were reported at the beginning of the infusion in two subjects, who recovered without sequelae. Conclusion. Repeated treatment of iron deficiency with iron isomaltoside 1000 could avoid episodes of IDA without major safety issues. PMID:25900645

Blood clearance and occupational exposure for 177Lu-DOTATATE compared to 177Lu-PSMA radionuclide therapy.

PubMed

Abuqbeitah, Mohammad; Demir, Mustafa; Uslu-Beşli, Lebriz; Yeyin, Nami; Sönmezoğlu, Kerim

2018-03-01

The main target of this work is to examine blood clearance and external exposure for 177 Lu-DOTATATE compared with new emerging 177 Lu-PSMA therapy. Blood clearance and radiation exposure of 31 patients treated with 5.5 ± 1.1 GBq 177 Lu-DOTATATE were compared to those of 23 patients treated with 7.4 GBq 177 Lu-PSMA. Dose rates were measured at several distances and time points up to 120 h after treatment. Blood samples were collected conjunctively after infusion. Caregiver's cumulative dose was measured by means of an OSL (optically stimulated luminescence) dosimeter for 4-5 days and medical staff's dose was also estimated using electronic personal dosimeters. Finger dose was determined via ring TLD (Thermoluminescence Dosimeter) for radiopharmacists and nurses. Dose rates due to 177 Lu-DOTATATE at a distance of 1 m, 4 h and 6 h after infusion, were 3.0 ± 2.8 and 2 ± 1.9 µSv/(h GBq), respectively, while those due to 177 Lu-PSMA were 3.1 ± 0.8 and 2.2 ± 0.9 µSv/(h GBq). Total effective dose of 17 caregivers was 100-200 µSv for 177 Lu-DOTATATE therapy. Mean effective doses to nurses and radiopharmacists were 5 and 4 µSv per patient, respectively, while those for physicists and physicians were 2 µSv per patient. For 177 Lu-DOTATATE, effective half-life in blood and early elimination phase were 0.31 ± 0.13 and 4.5 ± 1 h, while they were found as 0.4 ± 0.1 and 5 ± 1 h, respectively, for 177 Lu-PSMA. The first micturition time following 177 Lu-DOTATATE infusion was noted after 36 ± 14 min, while the second and third voiding times were after 74 ± 9 and 128 ± 41 min, respectively. It is concluded that blood clearance and radiation exposure for 177 Lu-DOTATATE are very similar to those for 177 Lu-PSMA, and both treatment modalities are reasonably reliable for outpatient treatment, since the mean dose rate [2.1 µSv/(h GBq)] decreased below the dose rate that allows release of the patient from the hospital (20 µSv/h) after 6 h at 1 m distance.

A framework for estimating radiation-related cancer risks in Japan from the 2011 Fukushima nuclear accident.

PubMed

Walsh, L; Zhang, W; Shore, R E; Auvinen, A; Laurier, D; Wakeford, R; Jacob, P; Gent, N; Anspaugh, L R; Schüz, J; Kesminiene, A; van Deventer, E; Tritscher, A; del Rosarion Pérez, M

2014-11-01

We present here a methodology for health risk assessment adopted by the World Health Organization that provides a framework for estimating risks from the Fukushima nuclear accident after the March 11, 2011 Japanese major earthquake and tsunami. Substantial attention has been given to the possible health risks associated with human exposure to radiation from damaged reactors at the Fukushima Daiichi nuclear power station. Cumulative doses were estimated and applied for each post-accident year of life, based on a reference level of exposure during the first year after the earthquake. A lifetime cumulative dose of twice the first year dose was estimated for the primary radionuclide contaminants ((134)Cs and (137)Cs) and are based on Chernobyl data, relative abundances of cesium isotopes, and cleanup efforts. Risks for particularly radiosensitive cancer sites (leukemia, thyroid and breast cancer), as well as the combined risk for all solid cancers were considered. The male and female cumulative risks of cancer incidence attributed to radiation doses from the accident, for those exposed at various ages, were estimated in terms of the lifetime attributable risk (LAR). Calculations of LAR were based on recent Japanese population statistics for cancer incidence and current radiation risk models from the Life Span Study of Japanese A-bomb survivors. Cancer risks over an initial period of 15 years after first exposure were also considered. LAR results were also given as a percentage of the lifetime baseline risk (i.e., the cancer risk in the absence of radiation exposure from the accident). The LAR results were based on either a reference first year dose (10 mGy) or a reference lifetime dose (20 mGy) so that risk assessment may be applied for relocated and non-relocated members of the public, as well as for adult male emergency workers. The results show that the major contribution to LAR from the reference lifetime dose comes from the first year dose. For a dose of 10 mGy in the first year and continuing exposure, the lifetime radiation-related cancer risks based on lifetime dose (which are highest for children under 5 years of age at initial exposure), are small, and much smaller than the lifetime baseline cancer risks. For example, after initial exposure at age 1 year, the lifetime excess radiation risk and baseline risk of all solid cancers in females were estimated to be 0.7 · 10(-2) and 29.0 · 10(-2), respectively. The 15 year risks based on the lifetime reference dose are very small. However, for initial exposure in childhood, the 15 year risks based on the lifetime reference dose are up to 33 and 88% as large as the 15 year baseline risks for leukemia and thyroid cancer, respectively. The results may be scaled to particular dose estimates after consideration of caveats. One caveat is related to the lack of epidemiological evidence defining risks at low doses, because the predicted risks come from cancer risk models fitted to a wide dose range (0-4 Gy), which assume that the solid cancer and leukemia lifetime risks for doses less than about 0.5 Gy and 0.2 Gy, respectively, are proportional to organ/tissue doses: this is unlikely to seriously underestimate risks, but may overestimate risks. This WHO-HRA framework may be used to update the risk estimates, when new population health statistics data, dosimetry information and radiation risk models become available.

Retrospective dose assessment for the population living in areas of local fallout from the Semipalatinsk nuclear test site Part I: External exposure.

PubMed

Gordeev, Konstantin; Shinkarev, Sergey; Ilyin, Leonid; Bouville, André; Hoshi, Masaharu; Luckyanov, Nickolas; Simon, Steven L

2006-02-01

A short analysis of all 111 atmospheric events conducted at the Semipalatinsk Test Site (STS) in 1949-1962 with regard to significant off-site exposure (more than 5 mSv of the effective dose during the first year after the explosion) has been made. The analytical method used to assess external exposure to the residents living in settlements near the STS is described. This method makes use of the archival data on the radiological conditions, including the measurements of exposure rate. Special attention was given to the residents of Dolon and Kanonerka villages exposed mainly as a result of the first test, detonated on August 29, 1949. For the residents of those settlements born in 1935, the dose estimates calculated according to the analytical method, are compared to those derived from the thermoluminescence measurements in bricks and electron paramagnetic resonance measurements in teeth. The methods described in this paper were used for external dose assessment for the cohort members at an initial stage of an ongoing epidemiological study conducted by the U.S. National Cancer Institute in the Republic of Kazakhstan. Recently revised methods and estimates of external exposure for that cohort are given in another paper (Simon et al.) in this conference.

Effects of cumulative risk on behavioral and psychological well-being in first grade: moderation by neighborhood context.

PubMed

Lima, Julie; Caughy, Margaret; Nettles, Saundra M; O'Campo, Patricia J

2010-10-01

This study builds upon existing research by examining whether risk indices for child psychological well-being behave in the same way in different types of neighborhoods. Specifically, we sought to determine if neighborhood characteristics acted to exacerbate or, alternatively, to buffer risk factors at the family and/or child level. Families with a child entering first grade in Fall 2002 were recruited from Baltimore City neighborhoods, defined as census block groups. This study included 405 children, and data came from an interview with the primary caregiver and an assessment of the first grader. The dependent variables were externalizing behavior and internalizing problems. A family risk index consisting of 13 measures, and a child risk index consisting of three measures were the main independent variables of interest. We examined the effects of these indices on child psychological well-being and behavior across two neighborhood characteristics: neighborhood potential for community involvement with children and neighborhood negative social climate. Results of multivariate analyses indicated that cumulative family risk was associated with an increase in both internalizing and externalizing behavior problems. Perceived negative social climate moderated the effect of family risks on behavior problems such that more risk was associated with a larger increment in both externalizing behavior problems and psychological problems for children living in high versus low risk neighborhoods. These findings further emphasize the importance of considering neighborhood context in the study of child psychological well-being. Copyright © 2010 Elsevier Ltd. All rights reserved.

Parent-child aggression, adult-partner violence, and child outcomes: A prospective, population-based study.

PubMed

Maneta, E K; White, M; Mezzacappa, E

2017-06-01

Parent-child physical aggression (PCPA) and adult intimate partner violence (IPV) are common forms of family violence that often co-occur. Their deleterious effects on children and adolescents have been well documented. However, important questions remain regarding whether the type of violence exposure, the experience of one or both forms, the chronicity of violent experiences, and the age, gender, and SES of the child, differentially influence developmental outcomes. Data on 2810 children from the Project on Human Development in Chicago Neighborhoods were analyzed. Children aged 3-9 at the outset were assessed three times, at 3-year intervals. Primary caregivers reported on IPV, PCPA, and children's externalizing and internalizing symptoms. Children's externalizing and internalizing symptoms were examined as a function of time, age, gender, socioeconomic status (SES), and the time-varying effects of cumulative IPV and PCPA exposure. Cumulative experiences of IPV and PCPA each adversely affected the developmental trajectories of both externalizing and internalizing symptoms, but in different ways; and they did so independently of participants' age, gender, or SES, which all functioned as significant, independent predictors of child outcomes. PCPA was by far the more potent of the two forms of violence; and when both forms occurred, they worked additively to affect outcomes. Important questions remain regarding the reasons for the differential potency of these two forms of family violence on childhood symptoms, and related implications for interventions, as well as for later adult behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

Commentary on Inhaled 239PuO 2 in Dogs — A Prophylaxis against Lung Cancer?

DOE PAGES

Cuttler, Jerry M.; Feinendegen, Ludwig E.

2015-01-01

Several studies on the effect of inhaled plutonium-dioxide particulates and the incidence of lung tumors in dogs reveal beneficial effects when the cumulative alpha-radiation dose is low. There is a threshold at an exposure level of about 100 cGy for excess tumor incidence and reduced lifespan. The observations conform to the expectations of the radiation hormesis dose-response model and contradict the predictions of the LNT hypothesis. These studies suggest investigating the possibility of employing low-dose alpha-radiation, such as from 239PuO 2 inhalation, as a prophylaxis against lung cancer.