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International Journal of Molecular... Oct 2019The lack of information on how biological systems respond to low-dose and low dose-rate exposures makes it difficult to accurately assess the carcinogenic risks. This is...
The lack of information on how biological systems respond to low-dose and low dose-rate exposures makes it difficult to accurately assess the carcinogenic risks. This is of critical importance to space radiation, which remains a serious concern for long-term manned space exploration. In this study, the γ-H2AX foci assay was used to follow DNA double-strand break (DSB) induction and repair following exposure to neutron irradiation, which is produced as secondary radiation in the space environment. Human lymphocytes were exposed to high dose-rate (HDR: 0.400 Gy/min) and low dose-rate (LDR: 0.015 Gy/min) (66)/Be(40) neutrons. DNA DSB induction was investigated 30 min post exposure to neutron doses ranging from 0.125 to 2 Gy. Repair kinetics was studied at different time points after a 1 Gy neutron dose. Our results indicated that γ-H2AX foci formation was 40% higher at HDR exposure compared to LDR exposure. The maximum γ-H2AX foci levels decreased gradually to 1.65 ± 0.64 foci/cell (LDR) and 1.29 ± 0.45 (HDR) at 24 h postirradiation, remaining significantly higher than background levels. This illustrates a significant effect of dose rate on neutron-induced DNA damage. While no significant difference was observed in residual DNA damage after 24 h, the DSB repair half-life of LDR exposure was slower than that of HDR exposure. The results give a first indication that the dose rate should be taken into account for cancer risk estimations related to neutrons.
Topics: DNA; DNA Breaks, Double-Stranded; DNA Repair; Dose-Response Relationship, Radiation; Fast Neutrons; Female; Histones; Humans; Lymphocytes; Male; Radiation, Ionizing; Time Factors
PubMed: 31661782
DOI: 10.3390/ijms20215350 -
Polymers Dec 2020In this study, a high-density polyethylene (HDPE)-based carbon fiber-reinforced thermoplastic (CFRTP) was irradiated by an electron-beam. To assess the absorbed dose...
Influences of Absorbed Dose Rate on the Mechanical Properties and Fiber-Matrix Interaction of High-Density Polyethylene-Based Carbon Fiber Reinforced Thermoplastic Irradiated by Electron-Beam.
In this study, a high-density polyethylene (HDPE)-based carbon fiber-reinforced thermoplastic (CFRTP) was irradiated by an electron-beam. To assess the absorbed dose rate influence on its mechanical properties, the beam energy and absorbed dose were fixed, while the absorbed dose rates were varied. The tensile strength (TS) and Young's modulus (YM) were evaluated. The irradiated CFRTP TS increased at absorbed dose rates of up to 6.8 kGy/s and decreased at higher rates. YM showed no meaningful differences. For CFRTPs constituents, the carbon fiber (CF) TS gradually increased, while the HDPE TS decreased slightly as the absorbed dose rates increased. The OH intermolecular bond was strongly developed in irradiated CFRTP at low absorbed dose rates and gradually declined when increasing those rates. X-ray photoelectron spectroscopy analysis revealed that the oxygen content of irradiated CFRTPs decreased with increasing absorbed dose rate due to the shorter irradiation time at higher dose rates. In conclusion, from the TS viewpoint, opposite effects occurred when increasing the absorbed dose rate: a favorable increase in CF TS and adverse decline of attractive hydrogen bonding interactions between HDPE and CF for CFRTPs TS. Therefore, the irradiated CFRTP TS was maximized at an optimum absorbed dose rate of 6.8 kGy/s.
PubMed: 33339384
DOI: 10.3390/polym12123012 -
The New England Journal of Medicine May 2022On January 2, 2022, Israel began administering a fourth dose of BNT162b2 vaccine to persons 60 years of age or older. Data are needed regarding the effect of the fourth...
BACKGROUND
On January 2, 2022, Israel began administering a fourth dose of BNT162b2 vaccine to persons 60 years of age or older. Data are needed regarding the effect of the fourth dose on rates of confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of severe coronavirus disease 2019 (Covid-19).
METHODS
Using the Israeli Ministry of Health database, we extracted data on 1,252,331 persons who were 60 years of age or older and eligible for the fourth dose during a period in which the B.1.1.529 (omicron) variant of SARS-CoV-2 was predominant (January 10 through March 2, 2022). We estimated the rate of confirmed infection and severe Covid-19 as a function of time starting at 8 days after receipt of a fourth dose (four-dose groups) as compared with that among persons who had received only three doses (three-dose group) and among persons who had received a fourth dose 3 to 7 days earlier (internal control group). For the estimation of rates, we used quasi-Poisson regression with adjustment for age, sex, demographic group, and calendar day.
RESULTS
The number of cases of severe Covid-19 per 100,000 person-days (unadjusted rate) was 1.5 in the aggregated four-dose groups, 3.9 in the three-dose group, and 4.2 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of severe Covid-19 in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 3.5 (95% confidence interval [CI], 2.7 to 4.6) and was lower than that in the internal control group by a factor of 2.3 (95% CI, 1.7 to 3.3). Protection against severe illness did not wane during the 6 weeks after receipt of the fourth dose. The number of cases of confirmed infection per 100,000 person-days (unadjusted rate) was 177 in the aggregated four-dose groups, 361 in the three-dose group, and 388 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of confirmed infection in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 2.0 (95% CI, 1.9 to 2.1) and was lower than that in the internal control group by a factor of 1.8 (95% CI, 1.7 to 1.9). However, this protection waned in later weeks.
CONCLUSIONS
Rates of confirmed SARS-CoV-2 infection and severe Covid-19 were lower after a fourth dose of BNT162b2 vaccine than after only three doses. Protection against confirmed infection appeared short-lived, whereas protection against severe illness did not wane during the study period.
Topics: BNT162 Vaccine; COVID-19; COVID-19 Vaccines; Humans; Israel; SARS-CoV-2
PubMed: 35381126
DOI: 10.1056/NEJMoa2201570 -
Radiation Research Mar 2015The biological risks associated with low-dose-rate (LDR) radiation exposures are not yet well defined. To assess the risk related to DNA damage, we compared the yields...
The biological risks associated with low-dose-rate (LDR) radiation exposures are not yet well defined. To assess the risk related to DNA damage, we compared the yields of two established biodosimetry end points, γ-H2AX and micronuclei (MNi), in peripheral mouse blood lymphocytes after prolonged in vivo exposure to LDR X rays (0.31 cGy/min) vs. acute high-dose-rate (HDR) exposure (1.03 Gy/min). C57BL/6 mice were total-body irradiated with 320 kVP X rays with doses of 0, 1.1, 2.2 and 4.45 Gy. Residual levels of total γ-H2AX fluorescence in lymphocytes isolated 24 h after the start of irradiation were assessed using indirect immunofluorescence methods. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to determine apoptotic cell frequency in lymphocytes sampled at 24 h. Curve fitting analysis suggested that the dose response for γ-H2AX yields after acute exposures could be described by a linear dependence. In contrast, a linear-quadratic dose-response shape was more appropriate for LDR exposure (perhaps reflecting differences in repair time after different LDR doses). Dose-rate sparing effects (P < 0.05) were observed at doses ≤2.2 Gy, such that the acute dose γ-H2AX and TUNEL-positive cell yields were significantly larger than the equivalent LDR yields. At the 4.45 Gy dose there was no difference in γ-H2AX expression between the two dose rates, whereas there was a two- to threefold increase in apoptosis in the LDR samples compared to the equivalent 4.45 Gy acute dose. Micronuclei yields were measured at 24 h and 7 days using the in vitro cytokinesis-blocked micronucleus (CBMN) assay. The results showed that MNi yields increased up to 2.2 Gy with no further increase at 4.45 Gy and with no detectable dose-rate effect across the dose range 24 h or 7 days post exposure. In conclusion, the γ-H2AX biomarker showed higher sensitivity to measure dose-rate effects after low-dose LDR X rays compared to MNi formation; however, confounding factors such as variable repair times post exposure, increased cell killing and cell cycle block likely contributed to the yields of MNi with accumulating doses of ionizing radiation.
Topics: Animals; Apoptosis; Cell Cycle; Cell Survival; DNA Damage; Dose-Response Relationship, Radiation; Gene Expression Regulation; Histones; Lymphocytes; Mice; Whole-Body Irradiation; X-Rays
PubMed: 25738897
DOI: 10.1667/RR13860.1 -
Journal of Applied Clinical Medical... Oct 2021A signal dependence on dose rate was reported for the ArcCHECK array due to recombination processes within the diodes. The purpose of our work was to quantify the...
PURPOSE
A signal dependence on dose rate was reported for the ArcCHECK array due to recombination processes within the diodes. The purpose of our work was to quantify the necessary correction and apply them to quality assurance measurements.
METHODS
Static 10 × 10 cm 6-MV fields delivered by a linear accelerator were applied to the detector array while decreasing the average dose rate, that is, the pulse frequency, from 500 to 30 MU/min. An ion chamber was placed inside the ArcCHECK cavity as a reference. Furthermore, the instantaneous dose rate dependence (DRD) was studied. The position of the detector was adjusted to change the dose-per-pulse, varying the distance between the focus and the diode closest to the focus between 69.6 and 359.6 cm. Reference measurements were performed with an ion chamber placed inside a PMMA slab phantom at the same source-to-detector distances ( . Exponential saturation functions were fitted to the data, with different parameters to account for two generations of ArcCHECK detectors (types 2 and 3) and both DRDs. Corrections were applied to 12 volumetric modulated arc therapy plans.
RESULTS
The sensitivity decreased by up to 2.8% with a decrease in average dose rate and by 9% with a decrease in instantaneous dose rate. Correcting the average DRD, the mean gamma pass rates (2%/2-mm criterion) of the treatment plans were improved by 5 percentage points (PP) for diode type 3 and 0.4 PP for type 2. Correcting the instantaneous DRD, the improvement was 8.4 PP for type 3 and 0.9 PP for type 2.
CONCLUSIONS
The instantaneous DRD was identified as the prevailing effect on the diode sensitivity. We developed and validated a method to correct this behavior. The number of falsely not passed treatment plans could be considerably reduced.
Topics: Humans; Particle Accelerators; Quality Assurance, Health Care; Radiometry; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Silicon
PubMed: 34519437
DOI: 10.1002/acm2.13409 -
BMC Ophthalmology Jun 2022To compare the recurrence rate of retinopathy of prematurity (ROP) after treatment with 0.3 mg vs. 0.25 mg ranibizumab.
OBJECTIVE
To compare the recurrence rate of retinopathy of prematurity (ROP) after treatment with 0.3 mg vs. 0.25 mg ranibizumab.
SUBJECTS
All patients with ROP who underwent intravitreal injection of ranibizumab in Hainan General Hospital between January 2014 and May 2020 were included in this retrospective study.
METHODS
Eighty-two cases (146 eyes) who received intravitreal injection of 0.25 mg ranibizumab were included in the conventional-dose group, and 59 cases (108 eyes) who received intravitreal injection of 0.3 mg ranibizumab were included in the high-dose group. The two groups were further divided into the 25-28-week, 29-31-week, 32-34-week, and 35-36-week GA subgroups. The differences between the conventional-dose group and the high-dose group in gestational age (GA), birth weight (BW), age at initial injection (weeks), incidence of systemic diseases, the recurrence rate of ROP, and age at retinal vascularization completed (weeks) were analyzed.
RESULTS
GA, BW, age at initial injection, and the incidence of systemic diseases were not significantly different between the conventional-dose group and the high-dose group (p > 0.05). The recurrence rates of ROP were significantly lower in the 25-28-week, 29-31-week, and 32-34-week subgroups of the high-dose group than in the same subgroups of the conventional-dose group (p < 0.05). Within the conventional-dose group, the recurrence rate of ROP was significantly lower in the 32-34-week and 35-36-week subgroups than in the 25-28-week and 29-31-week subgroups (p < 0.05). Within the high-dose group, the recurrence rate of ROP was not significantly different between the four subgroups (p > 0.05). Retinal vascularization was completed at a later age in the 32-34-week subgroup of the high-dose group than in the 32-34-week subgroup of the conventional-dose group (p < 0.05) but was not significantly different between the two groups at any other GA range (p > 0.05). No severe ocular or systemic complications occurred in any patient.
CONCLUSION
Treatment with 0.3 mg ranibizumab can reduce the recurrence rate of ROP without prolonging retinal vascularization or causing serious systemic complications. Therefore, this dose may be an appropriate therapeutic dose for ROP.
Topics: Angiogenesis Inhibitors; Bevacizumab; Gestational Age; Humans; Infant, Newborn; Intravitreal Injections; Ranibizumab; Retinal Neovascularization; Retinopathy of Prematurity; Retrospective Studies; Treatment Outcome
PubMed: 35729540
DOI: 10.1186/s12886-022-02489-6 -
Journal of Radiation Research Jan 2014This study examined the effects of continuous low-dose-rate radiation exposure (3.49 mGy/h) of gamma rays on mice testicles. C57BL/6 mice were divided into sham and...
This study examined the effects of continuous low-dose-rate radiation exposure (3.49 mGy/h) of gamma rays on mice testicles. C57BL/6 mice were divided into sham and radiation groups (n = 8 each), and were exposed to either sham irradiation or 2 Gy for 21 days, 0.2 Gy for 2 days, or 0.02 Gy for 6 h of low-dose-rate irradiation. Testicular weight, seminiferous tubular diameter, and seminiferous epithelial depth were significantly decreased in the mice irradiated with 2 Gy at 1 and 9 days after exposure. Moreover, the low-dose-rate radiation exposure induced an increase in malondialdehyde levels, and a decrease in superoxide dismutase activity in the testis of mice irradiated with 2 Gy at 1 and 9 days after exposure. The sperm count and motility in the epididymis also decreased in mice irradiated with 2 Gy at 1 and 9 days after exposure, whereas there was no significant effect on the proportion of abnormal sperm. The expressions of DNA methlytransferases-1 and histone deacetylases 1 in testes irradiated with 2 Gy were significantly decreased compared with the sham group. In conclusion, the damage exerted on the testes and epididymis largely depended on the total dose of low-dose-rate radiation.
Topics: Animals; DNA (Cytosine-5-)-Methyltransferase 1; DNA (Cytosine-5-)-Methyltransferases; Dose-Response Relationship, Radiation; Histone Deacetylase 1; Male; Mice; Mice, Inbred C57BL; Organ Size; Radiation Dosage; Reactive Oxygen Species; Spermatogenesis; Superoxide Dismutase; Testis
PubMed: 24027299
DOI: 10.1093/jrr/rrt090 -
Journal of Radiation Research Dec 2022The polymer gel dosimeter has been proposed for use as a 3D dosimeter for complex dose distribution measurement of high dose-rate (HDR) brachytherapy. However, various...
The polymer gel dosimeter has been proposed for use as a 3D dosimeter for complex dose distribution measurement of high dose-rate (HDR) brachytherapy. However, various shapes of catheter/applicator for sealed radioactive source transport used in clinical cases must be placed in the gel sample. The absorbed dose readout for the magnetic resonance (MR)-based polymer gel dosimeters requires calibration data for the dose-transverse relaxation rate (R2) response. In this study, we evaluated in detail the dose uncertainty and dose resolution of three calibration methods, the multi-sample and distance methods using the Ir-192 source and the linear accelerator (linac) method using 6MV X-rays. The use of Ir-192 sources increases dose uncertainty with steep dose gradients. We clarified that the uniformly irradiated gel sample improved the signal-to-noise ratio (SNR) due to the large slice thickness of MR images and could acquire an accurate calibration curve using the linac method. The curved tandem and ovoid applicator used for intracavitary irradiation of HDR brachytherapy for cervical cancer were reproduced with a glass tube to verify the dose distribution. The results of comparison with the treatment planning system (TPS) calculation by gamma analysis on the 3%/2 mm criterion were in good agreement with a gamma pass rate of 90%. In addition, the prescription dose could be evaluated accurately. We conclude that it is easy to place catheter/applicator in the polymer gel dosimeters, making them a useful tool for verifying the 3D dose distribution of HDR brachytherapy with accurate calibration methods.
Topics: Female; Humans; Uterine Cervical Neoplasms; Polymers; Nerve Tissue Proteins
PubMed: 36109319
DOI: 10.1093/jrr/rrac053 -
International Journal of Molecular... Nov 2022Ultra-high dose rate (UHDR) irradiation regimes have the potential to spare normal tissue while keeping equivalent tumoricidal capacity than conventional dose rate...
Ultra-high dose rate (UHDR) irradiation regimes have the potential to spare normal tissue while keeping equivalent tumoricidal capacity than conventional dose rate radiotherapy (CONV-RT). This has been called the FLASH effect. In this work, we present a new simulation framework aiming to study the production of radical species in water and biological media under different irradiation patterns. The chemical stage (heterogeneous phase) is based on a nonlinear reaction-diffusion model, implemented in GPU. After the first 1 μs, no further radical diffusion is assumed, and radical evolution may be simulated over long periods of hundreds of seconds. Our approach was first validated against previous results in the literature and then employed to assess the influence of different temporal microstructures of dose deposition in the expected biological damage. The variation of the Normal Tissue Complication Probability (NTCP), assuming the model of Labarbe et al., where the integral of the peroxyl radical concentration over time (AUC-ROO) is taken as surrogate for biological damage, is presented for different intra-pulse dose rate and pulse frequency configurations, relevant in the clinical scenario. These simulations yield that overall, mean dose rate and the dose per pulse are the best predictors of biological effects at UHDR.
Topics: Radiotherapy Dosage; Computer Simulation
PubMed: 36362271
DOI: 10.3390/ijms232113484 -
Precision Radiation Oncology Mar 2023EBT-XD model of Gafchromic films has a broader optimal dynamic dose range, up to 40 Gy, compared to its predecessor models. This characteristic has made EBT-XD films...
EBT-XD model of Gafchromic films has a broader optimal dynamic dose range, up to 40 Gy, compared to its predecessor models. This characteristic has made EBT-XD films suitable for high-dose applications such as stereotactic body radiotherapy and stereotactic radiosurgery, as well as ultra-high dose rate FLASH radiotherapy. The purpose of the current study was to characterize the dependence of EBT-XD film response on linear energy transfer (LET) and dose rate of therapeutic protons from a synchrotron. A clinical spot-scanning proton beam was used to study LET dependence at three dose-averaged LET (LET) values of 1.0 keV/µm, 3.6 keV/µm, and 7.6 keV/µm. A research proton beamline was used to study dose rate dependence at 150 Gy/second in the FLASH mode and 0.3 Gy/second in the non-FLASH mode. Film response data from LET values of 0.9 keV/µm and 9.0 keV/µm of the proton FLASH beam were also compared. Film response data from a clinical 6 MV photon beam were used as a reference. Both gray value method and optical density (OD) method were used in film calibration. Calibration results using a specific OD calculation method and a generic OD calculation method were compared. The four-parameter NIH Rodbard function and three-parameter rational function were compared in fitting the calibration curves. Experimental results showed that the response of EBT-XD film is proton LET dependent but independent of dose rate. Goodness-of-fit analysis showed that using the NIH Rodbard function is superior for both protons and photons. Using the "specific OD + NIH Rodbard function" method for EBT-XD film calibration is recommended.
PubMed: 37868341
DOI: 10.1002/pro6.1187