Early Biomarkers Associated with P53 Signaling for Acute Radiation Injury

Accurate dose assessment within 1 day or even 12 h after exposure through current methods of dose estimation remains a challenge, in response to a large number of casualties caused by nuclear or radiation accidents. P53 signaling pathway plays an important role in DNA damage repair and cell apoptosis induced by ionizing radiation. The changes of radiation-induced P53 related genes in the early stage of ionizing radiation should compensate for the deficiency of lymphocyte decline and γ-H2AX analysis as novel biomarkers of radiation damage. Bioinformatic analysis was performed on previous data to find candidate genes from human peripheral blood irradiated in vitro. The expression levels of candidate genes were detected by RT-PCR. The expressions of screened DDB2, AEN, TRIAP1, and TRAF4 were stable in healthy population, but significantly up-regulated by radiation, with time specificity and dose dependence in 2–24 h after irradiation. They are early indicators for medical treatment in acute radiation injury. Their effective combination could achieve a more accurate dose assessment for large-scale wounded patients within 24 h post exposure. The effective combination of p53-related genes DDB2, AEN, TRIAP1, and TRAF4 is a novel biodosimetry for a large number of people exposed to acute nuclear accidents.

Improved reconstruction methodology of clinical electron energy spectra based on Tikhonov regularization and generalized simulated annealing

Electron beam radiotherapy is the most widespread treatment modality todeal with superficial cancers. In electron radiotherapy, the energy spectrum isimportant for electron beam modelling and accurate dose calculation. Since thepercentage depth-dose (PDD) is a function of the beam’s energy, the reconstruction of the spectrum from the depth-dose curve represents an inverse problem.Thus, the energy spectrum can be related to the depth-dose by means of anappropriate mathematical model as the Fredholm equation of the first kind.Since the Fredholm equation of the first kind is ill-posed, some regularizationmethod has to be used to achieve a useful solution. In this work the Tikhonovregularization function was solved by the generalized simulated annealing optimization method. The accuracy of the reconstruction was verified by thegamma index passing rate criterion applied to the simulated PDD curves forthe reconstructed spectra compared to experimental PDD curves. Results showa good coincidence between the experimental and simulated depth-dose curvesaccording to the gamma passing rate better than 95% for 1% dose difference(DD)/1 mm distance to agreement (DTA) criteria. Moreover, the results showimprovement from previous works not only in accuracy but also in calculationtime. In general, the proposed method can help in the accuracy of dosimetryprocedures, treatment planning and quality control in radiotherapy.

Evaluation of chemotherapy preparation processes: Volumetric method reliability and gravimetric method utility within 5 US hospitals

Disclaimer In an effort to expedite the publication of articles , AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose The primary aim of this study was to investigate the accuracy of the volumetric method for intravenous (IV) preparations and explore the utility of gravimetric methods in the medication preparation process within multiple institutions. Secondary outcomes of this study were syringe size percent variations and impact on drug expenditures. Methods A prospective, noninterventional, multisite study was conducted between March 2015 and December 2016 to generate baseline estimates of accuracy and precision in the volumetric medication preparation process. Five hospitals in the United States were recruited for study participation. During the data collection process, technicians were required to measure the syringe at 3 different points: when the new empty syringe was connected to a closed-system transfer device (CSTD), when the filled syringe containing the prepared dose of medication was connected to a CSTD, and when the used syringe with residual medication was connected to a CSTD. The actual dose of drug dispensed (in mg) was divided by the specific gravity of the medication to determine the actual volume of medication dispensed. Results A total of 4,443 compounded sterile products representing 60 medications across 5 hospitals were eligible for the study. Of the evaluated preparations, 91.92% were within 5% of the prescribed dose and 96.56% were within 10% of the prescribed dose. The outliers ranged from –144.10% to 233.72%. Conclusion The potential for significant over- and undertreatment of an individual patient receiving IV chemotherapy exists, indicating the need for an additional measurement method, such as real-time gravimetric verification, to ensure an accurate dose is administered to every patient.

Development of Standard X-Ray Beams for Calibration of Radiobiology Cabinet and Conformal Irradiators

This work seeks to develop standard X-ray beams that are matched to radiobiology X-ray irradiators. The calibration of detectors used for dose determination of these irradiators is performed with a set of standard X rays that are more heavily filtered and/or lower energy, which leads to a higher uncertainty in the dose measurement. Models of the XRad320, SARRP, and the X-ray tube at the University of Wisconsin Medical Radiation Research Center (UWMRRC) were created using the BEAMnrc user code of the EGSnrc Monte Carlo code system. These models were validated against measurements, and the resultant modeled spectra were used to determine the amount of added filtration needed to match the X-ray beams at the UWMRRC to those of the XRad320 and SARRP. The depth profiles and half-value layer (HVL) simulations performed using BEAMnrc agreed to measurements within 3% and 3.6%, respectively. A primary measurement device, a free-air chamber, was developed to measure air kerma in the medium energy range of X rays. The resultant spectra of the matched beams had HVL's that matched the HVL's of the radiobiology irradiators well within the 3% criteria recommended by the International Atomic Energy Agency (IAEA) and the average energies agreed within 2.4%. In conclusion, three standard X-ray beams were developed at the UWMRRC with spectra that more closely match the spectra of the XRad320 and SARRP radiobiology irradiators, which will aid in a more accurate dose determination during calibration of these irradiators.

An integrated pipeline and multi-model graphical user interface for accurate nano-dosimetry

Accurate dosing of nanoparticles is crucial for risk assessment and for their safe use in medical and other applications. Although it is well-known that nanoparticles sediment, diffuse and aggregate as they move through a fluid, and that therefore the effective dose perceived by cells may not necessarily be that initially administered, dose quantification remains a challenge. This is because to date, methods for accurate dose estimation are difficult to implement, involving precise characterization of the nanomaterial and the exposure system as well as complex mathematical operations. Here we present a pipeline for accurate nano-dosimetry of engineered nanoparticles on cell monolayers, based on an easy-to-use graphical software - DosiGUI - which integrates two well-established particokinetic and particodynamic models. DosiGUI is an open source tool which was developed to facilitate nano-dosimetrics. The pipeline includes methods for determining the stickiness index which describes the affinity between nanoparticles and cells. Our results show that accurate estimations of the effective dose cannot prescind from rigorous characterization of the stickiness index, which depends on both nanoparticle characteristics and cell type.

A protocol for accurate radiochromic film dosimetry using Radiochromic.com

Background Radiochromic films have many applications in radiology and radiation therapy. Generally, the dosimetry system for radiochromic film dosimetry is composed of radiochromic films, flatbed scanner, and film analysis software. The purpose of this work is to present the effectiveness of a protocol for accurate radiochromic film dosimetry using Radiochromic.com as software for film analysis. Materials and methods Procedures for image acquisition, lot calibration, and dose calculation are explained and analyzed. Radiochromic.com enables state-of-the-art models and corrections for radiochromic film dosimetry, such as the Multigaussian model for multichannel film dosimetry, and lateral, inter-scan, and re-calibration corrections of the response. Results The protocol presented here provides accurate dose results by mitigating the sources of uncertainty that affect radiochromic film dosimetry. Conclusions Appropriate procedures for film and scanner handling in combination with Radiochromic.com as software for film analysis make easy and accurate radiochromic film dosimetry feasible.

Characterization with X-rays of a Large-Area GEMPix Detector with Optical Readout for QA in Hadron Therapy

Quality Assurance (QA) in hadron therapy is crucial to ensure safe and accurate dose delivery to patients. This can be achieved with fast, reliable and high-resolution detectors. In this paper, we present a novel solution that combines a triple Gas Electron Multiplier (GEM) and a highly pixelated readout based on a matrix of organic photodiodes fabricated on top of an oxide-based thin-film transistor backplane. The first LaGEMPix prototype with an active area of 60 × 80 mm2 was developed and characterized using low energy X-rays. The detector comprises a drift gap of 3.5 mm, a triple-GEM stack for electron amplification, and a readout featuring 480 × 640 pixels at a 126 µm pitch. Here, we describe the measurements and results in terms of spatial resolution for various experimental configurations. A comparison with GAFCHROMIC® films and the GEMPix detector used in the charge readout mode was performed to better understand the contribution to the spatial resolution from both the electron diffusion and the isotropic emission of photons. The measurements were compared to Monte Carlo simulations, using the FLUKA code. The simulation predictions are in good agreement with the GEMPix results. Future plans with respect to applications in hadron therapy are discussed.

Justification of approaches to organization of classes in the gym of students with low level of physical preparedness

The article is devoted to the optimization of the educational process in higher education institutions, in particular, to the improvement of physical education of students. The possibility of using special equipment (fitballs, weights, rubber shock absorbers, medballs, etc.) in the organization of classes in the gym is substantiated, the peculiarities of the organization of such classes are described. The state of health and physical fitness of higher education seekers in Ukraine is analyzed. It is established that the vast majority of students have a level of physical fitness below average. It was found that the system of organizing physical education classes in the gym with such students needs improvement. It is determined that there should be an individual approach for each student. It is emphasized that it is important to find an individual accurate dose of exercise, especially in the initial period of exercise, increasing it as the body adapts to exercise and improves fitness. We believe that the prospects for further research are to obtain experimental data that will assess the degree of impact of these types of classes on physical development and physical fitness of students

Treatment of Ocular Tumors Through a Novel Applicator on a Conventional Proton Pencil Beam Scanning Beamline

Treatment of ocular tumors on dedicated scattering-based proton therapy systems is standard afforded due to sharp lateral and distal penumbras. However, most newer proton therapy centers provide pencil beam scanning treatments. In this paper, we present a pencil beam scanning (PBS)-based ocular treatment solution. The design, commissioning, and validation of an applicator mount for a conventional PBS snout to allow for ocular treatments are given. In contrast to scattering techniques, PBS-based ocular therapy allows for inverse planning, providing planners with additional flexibility to shape the radiation field, potentially sparing healthy tissues. PBS enables the use of commercial Monte Carlo algorithms resulting in accurate dose calculations in the presence of heterogeneities and fiducials. The validation consisted of small field dosimetry measurements of point doses, depth doses, and lateral profiles relevant to ocular therapy. A comparison of beam properties achieved through the applicator against published literature is presented. We successfully showed the feasibility of PBS-based ocular treatments.