Journal articles on the topic 'Gamma beam diagnostics'

The ELI-NP (Extreme Light Infrastructure-Nuclear Physics) facility, currently under construction near Bucharest (Romania), is the pillar of the project ELI dedicated to the generation of high-brilliance gamma beams and high-power laser pulses that will be used for frontier research in nuclear physics. To develop an experimental program at the frontiers of the present-day knowledge, two pieces of equipment will be deployed at ELI-NP: a high power laser system consisting of two 10 PW lasers and a high brilliance gamma beam system. The ELI-NP Gamma beam system will deliver an intense gamma beam with unprecedented specifications in terms of photon flux, brilliance and energy bandwidth in an energy range from 0.2 to 20 MeV. Such a gamma beam requires special devices and techniques to measure and monitor the beam parameters during the commissioning and the operational phase. To accomplish this task, the Gamma Beam Characterization System, equipped with four elements, was developed: a Compton spectrometer (CSPEC), to measure and monitor the photon energy spectrum; a nuclear resonant scattering system (NRSS), for absolute beam energy calibration and inter-calibration of the other detectors; a beam profile imager (GPI) to be used for alignment and diagnostics purposes; and finally a sampling calorimeter (GCAL), for a fast combined measurement of the beam average energy and intensity. The combination of the measurements performed by GCAL and CSPEC allows fully characterizing the gamma beam energy distribution and intensity with a precision at the level of few per mill, enough to demonstrate the fulfillment of the required parameters. This article presents an overview of the gamma beam characterization system with focus on these two detectors, which were designed, assembled and are currently under test at INFN-Firenze. The layout and the working principle of the four devices is described, as well as some of the main results of detector tests.

The ELI-NP facility, currently being built in Bucharest, Romania, will deliver an intense and almost monochromatic gamma beam with tunable energy between 0.2 and 20 MeV. The challenging energy bandwidth of [Formula: see text]0.5% will be adjusted through the collimation system, while the main beam parameters will be measured through a devoted gamma-beam characterization system.[Formula: see text] The gamma-beam characterization system, designed by the EuroGammaS collaboration, consists of four elements: a Compton spectrometer that measures the gamma energy spectrum; a sampling calorimeter for a fast combined measurement of the beam average energy and its intensity, which will be used also as a monitor during machine commissioning and development; a nuclear resonant scattering system for absolute energy inter-calibration of the other detectors; and a gamma beam profile imager to be used for alignment and diagnostics purposes. The collimation and characterization system will be presented in this article. These systems have already been built and tested, while the delivery at ELI-NP facility and the final commissioning is scheduled by Fall 2018.

The paper presents the first experimental results obtained by using new gamma-quantum diagnostics for ion beam induced high energy density matter. Registration of γ-quantum output from the region of beam-target interaction with time resolution enables to pick-up information on density evolution of the target even if the ionization state of matter involved is unknown.

Analytical methods based on particle accelerators are widely used in cultural heritage diagnostics and archaeological sciences from the absolute dating of organic materials by means of radiocarbon accelerator mass spectrometry (AMS) to the analysis of the elemental composition of a wide range of materials (metals, obsidians, pottery) via ion beam analysis (IBA) techniques. At CEDAD (Centre for Dating and Diagnostics), the accelerator facility of the University of Salento, AMS 14C dating and PIXE (particle-induced X-ray emission)-PIGE (particle-induced gamma-ray emission) compositional analysis in external beam mode are combined to study certain archaeological materials. We present a review of the combined application of these analytical methods in the study of casting cores of the Riace bronzes, 2 classical Greek statues of extraordinary importance for the history of art.

We report on the technological commissioning of the Laser–Plasma Ion Accelerator section of the ELIMAIA user beamline at the ELI Beamlines facility in the Czech Republic. The high-peak, high-average power L3-HAPLS laser system was used with an energy of ~10 J and pulse duration of ~30 fs on target, both in single-pulse and high repetition-rate (~0.5 Hz) mode. The laser pulse was tightly focused to reach ultrahigh intensity on target (~1021 W/cm2) and sustain such laser–plasma interaction regime during high repetition-rate operations. The laser beam, ion beam, and laser–plasma emission were monitored on a shot-to-shot basis, and online data analysis at 0.5 Hz was demonstrated through the full set of used diagnostics (e.g., far and near field, laser temporal diagnostics, X- and gamma-ray detectors, Thomson Parabola ion spectrometer, time-of-flight ion detectors, plasma imaging, etc.). The capability and reliability of the ELIMAIA Ion Accelerator was successfully demonstrated at a repetition rate of 0.5 Hz for several hundreds of consecutive laser shots.

A TrueBeam STx is one of the most technologically advanced linear accelerators forradiotherapy and radiosurgery. The Monte Carlo simulation widely used in many applications in various fields such as nuclear physics, astrophysics, particle physics, and medicine. The Geant4/GATE Monte Carlo toolkit is developed for the simulation in imaging diagnostics, nuclear medicine, radiotherapy, and radiation biology to more accurately predict beam radiation dosimetry. In this work, we present the simulation results of the dosimetric characteristics of a 6 MV photon beam of TrueBeam STx medical LINAC using Monte Carlo Geant4/GATE. The percentage depth dose (PDD), central axis depth dose (Profile) have been simulated and compared with those measured in a water phantom for field sizes 10×10 cm2 via the gamma-index method. These results will permit to check calculation data given by the treatment planning system.

The possibility of organizing neutron therapy with a photoneutron beam produced by the electron accelerator target, and ensuring the required dose at the tumor at a reasonable exposure time and with minimal impact on patients investigated. Generation of neutrons from the target of electron accelerator takes place in two stages: e- ® γ ® n, and in the selected electron energy range of 20-100 MeV, the bremsstrahlung gamma radiation in many times (~ 3 orders of magnitude) offers more than “useful” neutron yield. This raises the problem of the selective control of the “harmful” for radiotherapy secondary gamma radiation while providing the minimum attenuation of the neutron flux in the output beam. In order to solve the general problem of the formation of a neutron beam with necessary spectral characteristics having sufficient intensity, there has been resolved a number of computational tasks of the selection of the optimal configuration of the output beam unit and its composition. The matter of high importance is to minimize additional irradiation of the patient from the bremsstrahlung (generated by electrons) and secondary gamma radiation (generated by neutrons) from the accelerator target as well as from output unit’s materials. On the other hand, at a generation stage e- ® γ the bremsstrahlung beam could be applied for effective radionuclide production by reactions (γ,n) and (γ,p) due to high leak intensity ~ 1.3·1017 photon/s. By the Mo100(γ,n)99Mo reaction the main diagnostic nuclide 99Tc could be produced sufficiently for the clinical needs. The resulting configuration of the output unit provides the required beam quality for the neutron capture therapy (NCT), which commonly assumed to be the only competitive technology of neutron therapy on the background of the massive invasion of proton therapy and other highly selective techniques that ultimately damage the target sparing the surrounding tissues and organs. For the accessible accelerator (average current 4 mA and electron energy 35 MeV) the flux density of epithermal photoneutrons (they required for NCT) in the beam at the output is of the order of magnitude or more higher than the typical yield from existing and planned reactors' beams. The proposed scheme of generation and extraction of photoneutrons for NCT has a number of strong advantages over traditional techniques: a) the applying of electron accelerators for neutron production is much safer and cheaper than conventional reactor beams in use; b) accelerator with the target, the beam output unit with the necessary equipment can be placed on the territory of the clinic without any problems of radiation safety; c) the proposed target – liquid gallium, which also serves as a cooler, is an “environmentally friendly” material due to low activation which rapidly (in ~ 4 days) falls to the background level.

Technologically-enhanced electronic image sensors are used in various fields as diagnostic techniques in medicine or space applications. In the latter case the devices can be exposed to intense radiation fluxes over time which may impair the functioning of the same equipment. In this paper we report the results of gamma-ray irradiation tests on CMOS image sensors simulating the space radiation over a long time period. Gamma-ray irradiation tests were carried out by means of IGS-3 gamma irradiation facility of Palermo University, based on 60Co sources with different activities. To reduce the dose rate and realize a narrow gamma-ray beam, a lead-collimation system was purposely built. It permits to have dose rate values less than 10 mGy/s and to irradiate CMOS Image Sensors during operation. The total ionizing dose to CMOS image sensors was monitored in-situ, during irradiation, up to 1000 Gy and images were acquired every 25 Gy. At the end of the tests, the sensors continued to operate despite a background noise and some pixels were completely saturated. These effects, however, involve isolated pixels and therefore, should not affect the image quality.

Particle beam radiography, which uses a variety of particle probes (neutrons, protons, electrons, gammas and potentially other particles) to study the structure of materials and objects noninvasively, is reviewed, largely from an accelerator perspective, although the use of cosmic rays (mainly muons but potentially also high-energy neutrinos) is briefly reviewed. Tomography is a form of radiography which uses multiple views to reconstruct a three-dimensional density map of an object. There is a very wide range of applications of radiography and tomography, from medicine to engineering and security, and advances in instrumentation, specifically the development of electronic detectors, allow rapid analysis of the resultant radiographs. Flash radiography is a diagnostic technique for large high-explosive-driven hydrodynamic experiments that is used at many laboratories. The bremsstrahlung radiation pulse from an intense relativistic electron beam incident onto a high-Z target is the source of these radiographs. The challenge is to provide radiation sources intense enough to penetrate hundreds of g/cm2 of material, in pulses short enough to stop the motion of high-speed hydrodynamic shocks, and with source spots small enough to resolve fine details. The challenge has been met with a wide variety of accelerator technologies, including pulsed-power-driven diodes, air-core pulsed betatrons and high-current linear induction accelerators. Accelerator technology has also evolved to accommodate the experimenters' continuing quest for multiple images in time and space. Linear induction accelerators have had a major role in these advances, especially in providing multiple-time radiographs of the largest hydrodynamic experiments.

Abstract The use of lead apron for radiation protection is regulated under the Indonesia Nuclear Regulatory Agency (BAPETEN) Decree no. 8 year 2011 about Radiation Safety and the Use of Diagnostic and Interventional Radiological X-Ray Machine. It listed the apron specifications are as follows: having thickness equivalent to 0.2 mm Pb or 0.25 mm Pb for diagnostic use and equivalent to 0.35 mm Pb or 0.5 mm Pb for interventional use. Further, National Standardization Agency (BSN) had issued SNI IEC 61331-1:2016, providing guidance for testing the plate materials on the apron using 400 kV x-ray machine and 1.3 MeV gamma exposure with narrow beam, to measure the attenuation ratio and air kerma rate. The method used is to determine the attenuation ratio, build-up factors, and equivalent attenuation coefficient. There were 4 different aprons (A, B, C, and D) with 9 measurement points. The results showed the air kerma rate without apron was 0.664 mGy/second, the air kerma rate with lead-equivalent layer was 0.0006 mGy/second, and the best result was produced using the apron C, with the attenuation ratio ranging from 17.2 to 29.1, showing the most homogeneity.

Bio-hybrid hydrogels consist of a water-swollen hydrophilic polymer network encapsulating or conjugating single biomolecules, or larger and more complex biological constructs like whole cells. By modulating at least one dimension of the hydrogel system at the micro- or nanoscale, the activity of the biological component can be extremely upgraded with clear advantages for the development of therapeutic or diagnostic micro- and nano-devices. Gamma or e-beam irradiation of polymers allow a good control of the chemistry at the micro-/nanoscale with minimal recourse to toxic reactants and solvents. Another potential advantage is to obtain simultaneous sterilization when the absorbed doses are within the sterilization dose range. This short review will highlight opportunities and challenges of the radiation technologies to produce bio-hybrid nanogels as delivery devices of therapeutic biomolecules to the target cells, tissues, and organs, and to create hydrogel patterns at the nano-length and micro-length scales on surfaces.

It has been long recognized that dual-energy imaging could help to enhance the detectability of lesions in diagnostic radiology, by removing the contrast of surrounding tissues. Furthermore, X-ray attenuation is material specific and information about the object constituents can be extracted for tissue characterisation, i.e., to assess whether lesions represent a malignant or benign process. However, a true separation between the low and high energy components is not possible with conventional sources because of their broad X-ray spectrum, and the artifacts produced in the subtracted image can be only partially removed. Finally, dose issues have also prevented so far the application of dual-energy techniques within the clinical context. Very recently, a new intense and monochromatic X-ray source was proposed to fill the gap between a synchrotron radiation facility and the standard X-ray tube. Indeed, inverse Compton scattering (ICS) sources, which are based on the interaction of a powerful laser beam and a bright beam of relativistic electrons, are among the most promising innovative sources of monochromatic X and gamma radiation. In this contribution, we review the main features that allow an ICS source to meet the requirements of a medical imaging application. Specific examples of K-edge subtraction are then provided, to show the potential of ICS in clinical applications that require intravenous injection of a contrast medium.

Technetium-99m (99mTc) is the most used radionuclide worldwide in nuclear medicine for diagnostic imaging procedures. 99mTc is typically extracted from portable generators containing 99Mo, which is produced normally in nuclear reactors as a fission product of highly enriched Uranium material. Due to unexpected outages or planned and unplanned reactor shutdown, significant 99mTc shortages appeared as a problem since 2008 The alternative cyclotron-based approach through the 100Mo(p,2n)99mTc reaction is considered one of the most promising routes for direct 99mTc production in order to mitigate potential 99Mo shortages. The design and manufacturing of appropriate cyclotron targets for the production of significant amounts of a radiopharmaceutical for medical use is a technological challenge. In this work, a novel solid target preparation method was developed, including sputter deposition of a dense, adherent, and non-oxidized Mo target material onto a complex backing plate. The latter included either chemically resistant sapphire or synthetic diamond brazed in vacuum conditions to copper. The target thermo-mechanical stability tests were performed under 15.6 MeV proton energy and different beam intensities, up to the maximum provided by the available GE Healthcare (Chicago, IL, USA) PET trace medical cyclotron. The targets resisted proton beam currents up to 60 µA (corresponding to a heat power density of about 1 kW/cm2) without damage or Mo deposited layer delamination. The chemical stability of the proposed backing materials was proven by gamma-spectroscopy analysis of the solution obtained after the standard dissolution procedure of irradiated targets in H2O2.

Currently, many semiconductor compounds, particularly Cd1-xZnxTe, have attracted attention for applications in detection of radiation, due to the very good resolution without cryogenic cooling (a 1.3 keV-FWHM at the 122 keV line from 57Co is reported for some detectors). In this study the properties of a zinc doped cadmium telluride detector mounted on a thermoelectric cooler (Amptek Inc., model XR-100T-CZT) were studied. The detection system is based on a Cd0.9Zn0.1Te crystal of 3x3x2 mm, which operates at approximately -21°C and uses a rise time discrimination (RTD) circuit to improve the energy resolution. Although the quantum efficiency of this compound is very high, the small dimensions of the crystal limit its use to low energy photons (some hundreds of keV). Because of the carrier trapping characteristics of CZT, the experimental determination of the response function is essential. In this work it was measured in the range of energies from 10 to 400 keV, employing gamma rays and fluorescence x-rays from different sources (57Co, 133Ba, 152Eu and 241Am). In spite of the experimental difficulties, the x-ray escape fraction was also evaluated, making it possible the correction of the distortion it causes in the measured spectra. Measurements of x-ray spectra produced by a tungsten tube operating at small currents were carried out, and the stripping procedure was performed, taking into account the two contributions (efficiency and escape fraction). Results obtained point to the feasibility of use of this detector for in-situ diagnostic x-ray spectroscopy, provided that low intensity beams are available.

Tuberculosis (TB) management is important for prompt discrimination of latent TB infection (LTBI) from active TB and proper treatment. Whole blood Interferon-gamma (IFN-γ) release assay (IGRA) is used to diagnose LTBI based on the secretion of IFN-γ by T-cells in the whole blood by using a specific antigen of Mycobacterium tuberculosis. However, the ability of IGRA to distinguish active TB from LTBI is considerably limited. Distinguishing active TB from LTBI is necessary to identify indicators that can be used to effectively manage TB and develop diagnostic methods. In the present study, we used a Luminex multiplex bead array (a bead-based antibody–antigen sandwich method). The whole blood level of acute phase proteins (APPs), such as endoglin (ENG), procalcitonin (PCT), C-reactive protein (CRP), and α1-acid glycoprotein (AGP), in active TB, LTBI, and healthy individuals were analyzed and quantified. The APP test results for the serum and whole blood samples showed that the levels of PCT, CRP, and AGP were significantly increased (p < 0.0500; area under curve = 0.955) in active TB. The level of these markers in the whole blood of active TB, LTBI, and healthy individuals could provide data for effective diagnosis and treatment of TB.

Background The etiology of allergic fungal rhinosinusitis (AFRS) remains controversial. Initially thought to represent an immunoglobulin E (IgE)–mediated hypersensitivity to fungal antigens, additional data have implicated other non-IgE and cellular-mediated pathways. The aim of this study was to characterize T-helper type 1 (Th1) and Th2 immune responses of blood lymphocytes from AFRS patients by fungal antigen stimulation to help differentiate these possible pathways. Methods Peripheral blood mononuclear cells (PBMCs) isolated from AFRS patients (n = 10) and healthy controls (HCs; n = 11) were exposed to four different fungal extracts (Alternaria, Aspergillus, Cladosporium, and Penicillium) in duplicate. After a 72-hour incubation, the supernatants were analyzed for cytokine levels of three Th1 (interferon [IFN] gamma, interleukin [IL]-2, and tumor necrosis factor alpha) and three Th2 (IL-10, IL-5, and IL-4) cytokines by cytometric bead array flow cytometry. Serum fungal-specific IgE levels were measured by ImmunoCAP (Pharmacia Diagnostics, Kalamazoo, MI). Results Fungal extracts of Alternaria and Cladosporium stimulated higher levels of IL-5 from PBMCs in AFRS when compared with HCs (p < 0.05). IL-4 was also elevated for Alternaria in AFRS versus HCs (p < 0.05). A skewed Th2 response to fungal antigen exposure was confirmed by an elevated IL-5/IFN-gamma ratio in AFRS subjects (p < 0.05). Initial studies suggest a correlation between percent T-cell activation and IL-5 expression to IgE levels. Fungal antigens stimulated a notable but not statistically significant increase in IL-10 response in HCs. Conclusion In AFRS patients, fungal antigens stimulated T-cell activation, inducing a predominately Th2 immune response. Healthy controls expressed an inhibitory cytokine IL-10 when exposed to these fungal antigens, possibly serving as a protective response.

Abstract NH and EE equally contributed. ADW and PB co-signed. The expression of fetal hemoglobin (HbF) is one of the main targets of sickle cell disease treatment, as it inhibits the polymerization of hemoglobin S. The hypothesis of an inhibitory threshold of HbF per red blood cell (RBC) has been suggested, 1 although not well defined, as the overall percentage of HbF does not reflect the heterogeneous distribution of HbF per cell. Likewise, the qualitative analysis of RBCs containing HbF, called F cells, is neither reproducible nor clinically interpretable, due to low expression. 2 We have developed a technique for measuring the amount of HbF per cell, to determine thresholds of HbF expression per RBC correlated with clinical and biological effects. 2 Among genes controlling its expression, BCL11A has a major repressive effect on the expression of gamma globin/HbF during the fetal to adult hemoglobin switch. Post-transcriptional silencing of BCL11A, using lentivirus expression of a shRNA embedded in a microRNA architecture (shmiR) to re-activate γ-globin expression, is safe and demonstrates high levels of %HbF in a pilot clinical study (NCT 03282656). 3 Here, we show the quantitative measurement of HbF per RBC and reticulocyte. Methods: During patient follow-up, HbF quantification per single cell RBC was performed using a fluorescent HbF antibody. 2 Addition of an anti-CD71 fluorescent antibody allowed selection of reticulocyte sub-populations for determining their HbF content. Fold-increase in percentage of RBC versus percentage of reticulocyte were calculated. Kinetics of HbF/RBC and HbF/Reticulocyte were modeled using mixed effects polynomial linear regression to account for the correlation between repeated data over time. Results: With a median follow-up of 15 months [12-20] after gene transfer, figure 1 shows the mathematical modeling of single-RBC HbF measurement representing RBC percentage containing at least 2, 4, 6, 8 and 10 pg of HbF. Percentage of RBC above each threshold was higher compared to 14 hydroxyurea treated patients for 6 months. Figure 2 shows fold increase between reticulocytes and RBCs with same thresholds of HbF/cell. For low thresholds, RBCs were found in same percentage as reticulocytes whereas RBCs containing increasing levels of HbF were found in higher percentage than reticulocytes, until 6pg/cell showing a clear selective advantage for red cells with a threshold ≥ 6pg/cell of HbF. Figure 3 shows different kinetics of HbF increase according to two different transduction strategies with 2 enhancers in patients 2-4 compared to one enhancer in patients 6-8. Conclusion: BCL11A down-regulation in six clinical trial subjects was associated with an in vivo selection process RBCs with ≥ 6pg HbF per cell attained with different engraftment kinetics, depending on transduction processes, and ultimately stable high level and broadly distributed HbF. 1 Steinberg MH, Chui DH, Dover GJ, Sebastiani P, Alsultan A. Fetal hemoglobin in sickle cell anemia: a glass half full? Blood. 2014 Jan 23;123(4):481-5. 2 Hebert N, Rakotoson MG, Bodivit G, et al. Individual red blood cell fetal hemoglobin quantification allows to determine protective thresholds in sickle cell disease. Am. J. Hematol. 3 Esrick EB, Lehmann LE, Biffi A, et al. Post-Transcriptional Genetic Silencing of BCL11A to Treat Sickle Cell Disease. N. Engl. J. Med. 2021;384(3):205-215. Figure 1 Figure 1. Disclosures Esrick: bluebird bio: Consultancy. Audureau: GBT: Honoraria. Higgins: Sebia, Inc.: Honoraria; Danaher Diagnostics: Consultancy. Williams: BioMarin: Membership on an entity's Board of Directors or advisory committees, Other: Insertion Site Advisory Board; Geneception: Membership on an entity's Board of Directors or advisory committees, Other: Scientific Advisory Board; Emerging Therapy Solutions: Membership on an entity's Board of Directors or advisory committees, Other: Chief Scientific Chair; Beam Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Scientific Advisory Board; Alerion Biosciences: Other: Co-founder (now licensed to Avro Bio, potential for future milestones/royalties); Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Steering Committee, Novartis ETB115E2201 (eltrombopag in aplastic anemia). Advisory fees donated to NAPAAC.; Orchard Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Membership on a safety advisory board (SAB): SAB position ended 05/20/2021. Co-founder , Patents & Royalties: Potential for future royalty/milestone income, X-SCID. Provided GMP vector for clinical trial, Research Funding; bluebird bio: Membership on an entity's Board of Directors or advisory committees, Other: Insertion Site Analysis Advisory Board, Patents & Royalties: BCH licensed certain IP relevant to hemoglobinopathies to bluebird bio. The current license includes the potential for future royalty/milestone income. Bluebird has indicated they will not pursue this as a clinical program and BCH is negotiating return of, Research Funding. Bartolucci: AGIOS: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Steering committee, Research Funding; Jazz Pharma: Other: Lecture fees; Emmaus: Consultancy; Addmedica: Consultancy, Other: Lecture fees, Research Funding; INNOVHEM: Other: Co-founder; Hemanext: Consultancy; GBT: Consultancy; Bluebird: Consultancy, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy; Fabre Foundation: Research Funding.

Objectives: Sepsis is one of the leading causes of morbidity and mortality within the healthcare system and remains a diagnostic and therapeutic challenge. A major issue in the diagnosis of sepsis is understanding the pathophysiologic mechanism, which revolves around host immune system activation and dysregulated responses. African Americans are more likely to experience severe sepsis with higher mortality rates compared to the general population. This pilot study characterized multiple inflammatory markers and proteases in plasma of primarily African American and Afro-Caribbean patients with mild sepsis. Methods: Plasma was collected from 16 healthy controls and 15 subjects presenting with sepsis, on admission, and again upon resolution of the signs of sepsis, defined as a resolution of sepsis criteria. Plasma samples were analyzed for cytokines, chemokines, and proteases using multiplex bead assays. Results: Elevated levels of granulocyte colony-stimulating factor, interleukin-10, interleukin-15, interleukin-1 receptor antagonist, interleukin-8, interferon gamma-induced protein 10, monocyte chemoattractant protein-1, matrix metallopeptidase 12, and cathepsin S were identified in plasma from sepsis patients on admission compared to control subjects. Interleukin-6, interleukin-8, granulocyte colony-stimulating factor, and cathepsin S were reduced in sepsis patients upon clinical resolution of sepsis. Conclusion: These findings profile the circulating inflammatory cytokines, chemokines, and proteases in African Americans and Afro-Caribbean patients during sepsis. The role of these targets in sepsis needs addressing in this patient population.

18530 Background: To determine the cytokine expression profiles of patients with AML and NHL using a sensitive bead-based Luminex multiplex assay in a routine clinical diagnostic setting. Methods: Blood (plasma/serum) samples were collected from ten AML and five NHL patients. Six control samples from patients diagnosed as non-neoplastic/non-autoimmune/non-inflammatory were also analyzed for comparison. All samples were frozen prior to analysis. Using a bead-based Luminex assay (Human Cytokine 8-Plex Assay, Bio- Rad, Hercules, CA) we analyzed these samples for a panel of cytokines (IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-gamma, and TNF-alpha). This assay uses polystyrene microspheres, which provides simultaneous quantitation of these cytokines in a single sample. The expression levels were presented in picograms/mL. Average values for each of these markers were obtained for each group of patients (AML versus NHL versus Controls), and their expression levels were compared using χ2 analysis. Results: Overall, there was a significant difference in the expression profiles of all these cytokines among three patients groups (χ2, P < 0.001). All cytokines were consistently expressed at low levels in NHL patients as compared to control group. However, the levels of IL-6 and IL-8 were increased by 2.7 and 5.8 times, respectively in AML patients as compared to controls. Conclusions: The low levels of cytokines in NHL and AML patients suggest suppressed immune system in these two disease conditions; however, these findings warrant further studies to explore the underlying mechanisms for the increased levels of IL-6 and IL-8 in AML patients. Currently, studies are in progress to compare the levels of cytokines measured by Luminiex assay in different stages of leukemias and lymphomas (initial, post treatment and recovery phase etc.). These studies are partially funded by grants from the National Institute of Health/National Cancer Institute (RO1-CA98932–01 and U24-CA086359). No significant financial relationships to disclose.

Classification of primary CNS tumours is currently achieved by complementing histologic analysis with molecular information, in accordance with the WHO guidelines, and aims at providing accurate prognosis and optimal patient management. cIMPACT-NOW update 3 now recommends grading diffuse IDH-wild type astrocytomas as grade IV glioblastomas if they bear one or more of the following molecular alterations: EGFR amplification, TERT promoter mutation, and whole-chromosome 7 gain combined with chromosome 10 loss. In this reanalysis of the Cancer Genome Atlas (TCGA) glioma expression datasets, we identified 14 IDH-wt infiltrating astrocytic gliomas displaying a “normal-like (NL)” transcriptomic profile associated with a longer survival rate. Some of these tumours would be considered as GBM-equivalents with the current diagnostic algorithm. A k-nearest neighbors model was used to identify 3-gene signatures able to identify NL IDH-WT gliomas. Genes such as C5AR1 (complement receptor) SLC32A1 (vesicular gamma-aminobutyric acid transporter), and SMIM10L2A (long non-coding RNA) were overrepresented in these signatures which were validated further using the Chinese Glioma Genome and Ivy Glioblastoma Atlases. They showed high discriminative power and correlation with survival. This finding could lead to the validation of an immunohistochemical or PCR test which would facilitate classification of IDH-WT astrocytomas with unclear histological grading. Furthermore, associated signaling pathways might represent novel treatment targets for aggressive tumours.LEARNING OBJECTIVESThis presentation will enable the learner to: 1.Reconsider recent updates in the WHO classification of infiltrating gliomas.2.Discuss advanced bioinformatics profiling of the brain cancer transcriptome.

Background. Current management of treating iodine-negative metastases of differentiated thyroid cancer has its features. In recent years, tyrosine kinase inhibitors (sorafenib, sunitinib) have been registered and indicated to treat refractory forms of differentiated thyroid cancer in Ukraine. However, there were only few studies dealing with cytologic aspects of predicting radioiodine resistance of papillary thyroid cancer, development of radionuclide monitoring and diagnostic algorithm to detect relapses and metastases in patients with iodine-negative forms of differentiated thyroid cancer. At the same time, scientific and clinical aspects of treatment of radioiodineresistant differentiated thyroid cancer in Ukrainian oncology and radiology are barely studied. Thus, the status of treatment and post-therapeutic monitoring of patients with iodine-negative forms of differentiated thyroid cancer, still remains insufficiently studied and requires further scientific and clinical development. Purpose – develop a technique of treatment of iodine-negative metastases of differentiated thyroid cancer. Materials and methods. Thirty-eight patients with iodine-negative metastases of differentiated thyroid cancer were provided with treatment, where in 10 patients the efficiency of treatment was assessed by means of whole body scintigraphy with 99mTc-MIBI, in 10 patients – with 99mTcDMCA. In 10 patients the short-term results of treatment with tyrosine kinase inhibitors were evaluated by PET with 18F-FDG. Eight patients represented a group where the bones were affected and treatment was provided by means of radionuclide or external-beam radiotherapy. The average age of patients varied from 43 to 76, the median was 57.8 + 3.9; out of those: 24 women, 14 men. Pathohistologically, papillary cancer was diagnosed in 31, follicular – in 5, papillary-follicular – in 2. The studies were performed by means of the two-detector gamma camera manufactured by Mediso (Hungary) and the single-photon emission computed tomography (SPECT) E. CAM 180, Siemens (Germany). PET/CT were performed on the Biograph-64-TruePoint-Siemens combined tomograph (Germany), according to the guidelines of the European Association of Nuclear Physicians. Results. Prior to initiating therapy, 10 patients with differentiated thyroid cancer underwent whole body scintigraphy with 99mTc-MIBI and re-examination in three months in order to assess treatment success. After diagnostic examination, the patient was prescribed targeted therapy with Nexavar according to the treatment protocol. Regression of the focus in the lungs was achieved within 70 %. Further monitoring of antitumor treatment success was performed by means of whole body scintigraphy with 99mTc-MIBI. Ten patients, who had PET/CT with 18F-FDG made before treatment, also underwent targeted therapy by means of Nexavar. Diagnostic scanning with 18F-FDG after therapy revealed decreased functional activity of the lesion in the neck, however no decrease in the dimensions of the lesion was observed. Conclusions. Treatment of iodine-negative metastases of differentiated thyroid cancer by means of tyrosine kinase inhibitors was accompanied by a decreasing number of metastatic foci and reducing level of their functional activity. The studies have confirmed the possibility of applying techniques with non-iodine RP (99mTc-MIBI, 99mTc-DMCA) to assess the effectiveness of treatment of iodine-negative metastases of differentiated thyroid cancer . PET/CT with 18F-FDG is a highly informative technique for assessing the effect of tyrosine kinase inhibitors on the functional activity of metastatic foci according to metabolic scans in treatment of iodine-negative metastases of differentiated thyroid cancer. If there are no positive changes after 3–4 courses, external-beam radiotherapy with total radiation dose of 30–50 Gy is indicated, which is capable of reducing the volume of metastatic foci as well as their metabolic activity. The social and economic significance of the obtained findings have made it possible to improve the overall and recurrence-free survival rates in the working population of patients with differentiated thyroid cancer and reduce the cost of following-up patients with iodine-negative forms of differentiated thyroid cancer.

AimIt’s been reported that pro-inflammatory cytokines are elevated in patients with diabetic retinopathy (DR); this may contribute to the pathophysiology of the disease. The aim of this study is to measure the concentration of various inflammatory cytokines from the main CD4+ T helper inflammatory responses in blood serum from Mexican patients with DR in different stages using cytometric bead array (CBA) technology and correlate them with the presence and severity of DR in order to find possible DR biomarkers that serve as diagnostic or therapeutic predictors.Methods64 subjects were included in the study, 16 in the control group, 16 in the type 2 diabetes mellitus no DR (NDR) group, 16 in the non-proliferative DR (NPDR) group and 16 in the proliferative DR (PDR) group. Cytokine concentrations of interleukin (IL) 1ß, IL‐2, IL‐4, IL‐6, IL‐8, IL‐10, IL‐12, IL‐17A, tumour necrosis factor alpha (TNFα) and interferon-gamma in serum samples were measured using Human Inflammatory and TH1/TH2/TH17 CBA Kit.ResultsIL-6, IL-12, IL-17a and TNFα were significantly higher in the patients with DR compared with the control group. The PDR group showed a slightly lower concentration of serum cytokines IL-6, IL-12 and IL-17a. TNFα showed a higher concentration compared with healthy controls, NDR and NPDR subjects. We also found a positive statistical correlation between the presence and severity of DR with the clinical parameters haemoglobin A1c, body mass index and serum creatinine and the concentration of serum cytokines IL-6 and TNFα.ConclusionOur findings suggest that patients with diabetes and DR have a stronger chronic inflammatory profile compared with non-diabetic subjects.

ABSTRACTThe exoproteome ofStaphylococcus aureuscontains enzymes and virulence factors that are important for host adaptation. We investigated the exoprotein profiles and cytokine/chemokine responses obtained in three differentS. aureus-host interaction scenarios by using two-dimensional gel electrophoresis (2-DGE) and two-dimensional immunoblotting (2D-IB) combined with tandem mass spectrometry (MS/MS) and cytometric bead array techniques. The scenarios includedS. aureusbacteremia, skin and soft tissue infections (SSTIs), and healthy carriage. By the 2-DGE approach, 12 exoproteins (the chaperone protein DnaK, a phosphoglycerate kinase [Pgk], the chaperone GroEL, a multisensor hybrid histidine kinase, a 3-methyl-2-oxobutanoate hydroxymethyltransferase [PanB], cysteine synthase A, anN-acetyltransferase, four isoforms of elongation factor Tu [EF-Tu], and one signature protein spot that could not be reliably identified by MS/MS) were found to be consistently present in more than 50% of the bacteremia isolates, while none of the SSTI or healthy-carrier isolates showed any of these proteins. By the 2D-IB approach, we also identified five antigens (methionine aminopeptidase [MetAPs], exotoxin 15 [Set15], a peptidoglycan hydrolase [LytM], an alkyl hydroperoxide reductase [AhpC], and a haptoglobin-binding heme uptake protein [HarA]) specific for SSTI cases. Cytokine and chemokine production varied during the course of different infection types and carriage. Monokine induced by gamma interferon (MIG) was more highly stimulated in bacteremia patients than in SSTI patients and healthy carriers, especially during the acute phase of infection. MIG could therefore be further explored as a potential biomarker of bacteremia. In conclusion, 12 exoproteins from bacteremia isolates, MIG production, and five antigenic proteins identified during SSTIs should be further investigated for potential use as diagnostic markers.

Myeloma precursors (monoclonal gammopathy of unknown significance (MGUS) and smoldering myeloma (SMM)) precede the development of active multiple myeloma. Understanding the genomic and immune mechanisms that underlie transformation to MM may be key to identifying a successful therapy. To this end, we designed a prospective observational study of MGUS/SMM patients to identify genomic, immunological, and clinical parameters that may predict disease progression, and to recognize potential therapeutic targets for MGUS and SMM patients at high-risk of progression. From December 2015 until April 2019, 132 patients were consented, 100 patients were eligible for the study (41 MGUS, 59 SMM) and included in this analysis. Patients met the current definition of MGUS/SMM per IMWG criteria and were followed at a minimum of every 6 months with standard blood work and urine studies. All patients had advanced imaging/bone marrow biopsy at baseline and after 3 years of follow up. Median follow up time is 24 months (12-48 months). As of 07/01/2020, ten patients (17%, 10/59 SMM and 0%, 0/41 MGUS) progressed to MM and two patients progressed to systemic AL amyloidosis (3%, 2/59 SMM and 0%, 0/41 MGUS). Eight pairs of CD138+ bone marrow samples at baseline and at progression were available and analyzed by flow cytometry using a pre-designed antibody panel. Whole exome sequencing has been performed on 76 samples (matched germline and tumor) from 38 patients (15 MGUS, 17 SMM without progression and 6 SMM that progressed). A total of 24/39 (62%) tumor samples were covered at &gt;100x and 20/37 (54%) germline samples were covered at &gt;50x. After quality control analysis, bulk RNASeq of 144 samples from tumor and microenvironment (TME) cells from 90 patients (38 MGUS and 52 SMM) were included in the analysis. Flow analysis showed upregulation of inhibitory ligands (PD-L1/PD-L2) and B7-H3, CD200, HLA-E, HLA-G and CD59 at progression compared to baseline in 8 paired tumor samples from SMM patients that progressed. (Figure 1A). WES data analysis showed mutations in KMT2C/E (6/38, 4 SMM, 2 MGUS), NRAS/KRAS (5/38, 2 SMM progressors, 1 SMM, 2 MGUS), and FOXO3 (5/38, 1 SMM progressor, 2 SMM, 2 MGUS). Notably, 5/6 mutations in KMT2C/2E were deleterious mutations, all FOXO3 mutations were truncating, and mutations in KMT2C/2E, FOXO3, and NRAS were mutually exclusive. Unsupervised clustering of CD138+ tumor cells RNAseq at baseline identified 3 distinct clusters (C1-C3). All SMM that progressed (n=6) belonged to C2. CD138- TME RNAseq baseline samples were separated into 4 clusters (C1-C4) and 9/11 progressed patients belonged to C2 with distinct expression profiles (Figure 1 panel B/C). Immune deconvolution of TME samples showed lower baseline counts of CD8+ and CD4+ memory resting T cells and higher CD4+ memory activated, gamma delta T cells and dendritic cells in patients with PD (n=11) vs no PD (n=73)(p&lt;0.05). In progressors (n=11), monocytes and NK cells were increased whereas CD4+ naïve, gamma delta T cells, endothelial cells and fibroblasts were decreased at progression compared to baseline (p&lt;0.05). In tumor cells at baseline (n=6 PD; n=27 non-PD), the expression of immune checkpoint genes CD80, CD40, CD70, IL-2, OX40, IFIT1/2/3 was lower and of CCL5 was higher in patients with PD vs stable disease (SD). At baseline in TME cells, PD patients (n=11) had lower expression of immune checkpoint genes CD44, IL7R, CL5 and higher expression of CD276, CD70, CXCL9 compared to non-progressors (n=73) (p&lt;0.05). In progressors (n=11), increased expression of ICOS, CD80, TGFB1, GZMA, GZMB, CD86, HLA-E, HLA-F, CCL5 was observed at progression vs baseline (figure 1 panel D). Overall, we found extensive changes in the TME composition, in the expression of genes in immune pathways, and in the expression of immune checkpoints, both in tumor and TME samples at baseline and during disease progression. The results of clustering analysis suggest that the features of both tumor and TME at baseline could be possibly used to predict risk of disease progression. Larger studies and validation are needed. Treatment that targets changes in the cell composition and expression of immune checkpoints in myeloma precursor disease may be entertained as a possible therapeutic option. Disclosures Manasanch: Novartis: Research Funding; Sanofi: Research Funding; Takeda: Honoraria; JW Pharma: Research Funding; Merck: Research Funding; Adaptive Biotechnologies: Honoraria; GSK: Honoraria; Sanofi: Honoraria; BMS: Honoraria; Quest Diagnostics: Research Funding. Lee:Genentech: Consultancy; Regeneron: Research Funding; Daiichi Sankyo: Research Funding; Sanofi: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Genentech: Consultancy; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Amgen: Consultancy, Research Funding. Patel:Cellectis: Research Funding; Janssen: Consultancy, Research Funding; Nektar: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Oncopeptides: Consultancy; Precision Biosciences: Research Funding; Poseida: Research Funding; Celgene: Consultancy, Research Funding. Kaufman:Janssen: Research Funding; Bristol Myers Squibb: Research Funding; Karyopharm: Honoraria. Bashir:Celgene: Research Funding; KITE: Other: Advisory Board; Amgen: Other: Advisory Board; Purdue: Other: Advisory Board; Takeda: Other: Advisory Board, Research Funding; Acrotech: Research Funding; StemLine: Research Funding. Nieto:Novartis: Other: Grant Support; Astra Zeneca: Other: Grant Support; Affimed: Consultancy, Other: Grant Support; Secura Bio: Other: Grant Support. Qazilbash:Angiocrine: Research Funding; Bioline: Research Funding; Bioclinica: Consultancy; Amgen: Research Funding; Janssen: Research Funding. Berry:Berry Consultants LLC.: Other: Co-owner. Thomas:BMS: Research Funding; Ascentage: Membership on an entity's Board of Directors or advisory committees, Research Funding; X4 Pharma: Research Funding; Xencor: Research Funding; Pharmacyclics: Other: Advisory Boards; Genentech: Research Funding. Orlowski:STATinMED Research: Consultancy; Founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current submission.: Current equity holder in private company, Patents & Royalties; Sanofi-Aventis, Servier, Takeda Pharmaceuticals North America, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Inc., AstraZeneca, BMS, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis Pharmaceuticals, Inc., Janssen Biotech, Juno Therapeutics, Kite Pharma, Legend Biotech USA, Molecular Partners, Regeneron Pharmaceuticals, Inc.,: Honoraria, Membership on an entity's Board of Directors or advisory committees; Laboratory research funding from BioTheryX, and clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding. Neelapu:Cell Medica/Kuur: Other: personal fees; Legend Biotech: Other; Calibr: Other; Incyte: Other: personal fees; Bristol-Myers Squibb: Other: personal fees, Research Funding; Merck: Other: personal fees, Research Funding; Kite, a Gilead Company: Other: personal fees, Research Funding; Takeda Pharmaceuticals: Patents & Royalties; Unum Therapeutics: Other, Research Funding; Karus Therapeutics: Research Funding; Novartis: Other: personal fees; N/A: Other; Precision Biosciences: Other: personal fees, Research Funding; Cellectis: Research Funding; Acerta: Research Funding; Allogene Therapeutics: Other: personal fees, Research Funding; Poseida: Research Funding; Celgene: Other: personal fees, Research Funding; Pfizer: Other: personal fees; Adicet Bio: Other.

Genotoxic Effects of Radiofrequency-Electromagnetic Fields. IntroductionRadiation is energy emission in the form of electromagnetic waves emitted from the solar system and natural resources on earth. The currents produced by the elementary particles formed by the electric current create the magnetic field. Earth's surface is under the influence of the geomagnetic field emanating from the sun. However, the outer liquid also has a magnetic field created as a result of heat transfer in the core. Therefore, all living organisms on earth live under the influence of electromagnetic fields (EMF). Today, besides these natural energy resources, rapidly developing technological developments provide most of the convenience in our lives and expose people to artificial electromagnetic fields. However, man's magnetic field is also under the influence of other natural and artificial magnetic fields around him. In particular, by ionizing radiation, which carries enough energy to break down the genetic material, die cells as a result of DNA damaging, and other diseases, especially cancer, can develop as a result of tissue damage. Electromagnetic Fields in Our LivesToday, apart from natural geomagnetic fields, radiation is emitted from many technological devices. The spectrum of these fields includes many different types of radiation, from subatomic radiation such as gamma and X-rays to radio waves, depending on their wavelengths. Though, as a result of the rapid increase of technological growth, the duration and amount of exposure to EMF is also steadily increasing. On the other hand, wireless gadgets such as computers, smartphones and medical radiological devices have become a necessity for humans. Almost everyone is exposed to radiofrequency electromagnetic fields (RF-EMF) from cell phone and base station antennas or other sources. Thus, the damage caused by the radiation to the environment affects living organisms even many kilometres away unlimitedly. All organisms in the world live under the influence of these negative environmental changes and a large part of the world population is exposed to radiofrequency (RF) radiation for a long time in their daily lives. So, though we are not aware of it, our organs and tissues are constantly exposed to radiation. Therefore, radiation adversely affects human, animal and plant health and disrupts the environment and ecological balance. An example of negative effects, radiation can cause genetic changes in the body (Figure 1). Radiation is divided into ionizing and non-ionizing. Ionizing radiations cause electron loss or gain in an atom or group of atoms in the medium they pass through. Thus, positively or negatively charged ions are formed. High energy X, gamma, ultraviolet and some visible rays in the ionized region of the electromagnetic spectrum can be counted. Since gamma rays, X rays and ultraviolet rays can ionize the molecules in living things more, they can easily disrupt the chemical structure of tissues, cells and DNA molecules in living organisms. Therefore, they can be very dangerous and deadly to living things. The energy of the waves in the non-ionizing region of the electromagnetic spectrum is low and the energy levels are insufficient for the ionization of molecules. Electricity, radio and TV waves, microwaves, and infrared rays are not ionizing because they have low energy. Waves emitted from electronic devices (cell phones, computers, microwave ovens, etc.) are absorbed by the human and animal body. The amount of energy absorbed by the unit biological tissue mass per unit time is called the specific absorption rate (SAR), and its unit is W/kg. Risks of Electromagnetic Fields on Living ThingsDepending on the structure of the tissues and organs, the radiation must reach a certain threshold dose for the effect to occur. Radiation levels below the threshold dose are not effective. Depending on the structure of the tissues and organs, the radiation must reach a certain threshold dose. The effects of small doses of waves are negligible. However, the clinical effects of waves above a certain threshold may increase. High dose waves can cause cell death in tissues. Damages in the cell may increase the risk of cancer and hereditary damage after a while, and somatic effects in people exposed to radiation may cause cancer to appear years later. There is much research on the effects of RF fields. In vitro and in vivo studies on rats, plants and different tissues of humans; suggests that the RF fields are not genotoxic and the fact that harmful effect is due to the heat effect. The contradictory results on this issue have brought about discussions. Therefore, there are still concerns about the potential adverse effects of RFR on human health. A good understanding of the biological effects of RF radiation will protect against potential damages. Due to these uncertainties, with the electromagnetic field project of the World Health Organization, experimental and modelling studies on the biological effects of RF radiation have been accelerated. In 2011, the International Agency for Research on Cancer decided that RF-EMR waves could be potentially carcinogenic to humans (2). Considering that almost everyone, including young children, uses mobile phones in addition to other technological devices, the danger of electromagnetic waves has increased social interest. Genotoxic Effects of EMFIn addition to stimulating apoptosis and changes in ion channels, RF-EMF waves also have a potential effect on genetic material. The radiation absorbed by organisms causes the ionization of target molecules. In particular, biological damage may occur as a result of stimulation/ionization of atoms and disruption of molecular structures while ionizing radiation passes through tissue. As a result of ionization in the cell, electron increases and free electrons cause damage, especially in macromolecules and DNA. Free electrons move directly or indirectly. Free electrons directly affect the phosphodiester or H-bonds of DNA. As a result, the phosphodiester bonds of DNA in the cell are broken, single or double-stranded breakages and chemical toxins increase. DNA double-strand breaks are the most relevant biologic damage induced by ionizing radiation (3,4). There are no cells that are resistant to radiation. The nucleus of the cell and especially the chromosomes in dividing cells are very sensitive to radiation. One of the most important effects of radiation on the cell is to suppress cell growth. In particular, growth is impaired in cells exposed to radiation during cell division (mitosis). Consequently, cells with a high division rate are more sensitive to radiation. DNA damage in somatic cells can lead to cancer development or cell death. Cell death can occur as a result of breaking down DNA because ionizing radiation has enough energy to break down the cell's genetic material. Thus, tissues are damaged and cancer development may be triggered. DNA damage caused by radiation in cells is repaired by metabolic repair processes. If the breaks in DNA as a result of DNA damage caused by radiation in cells are not too large, they can be repaired by metabolic repair processes. Still, errors may occur during this repair. Chromosomes containing different genetic codes and information may also occur. In the cell, the released electrons interact with water molecules, indirectly causing the water to be reactively divided into two parts. Free radicals carry an electron that is not electrically shared in their orbits. Free radicals can cause genetic damage in DNA such as nucleotide changes, double and single-strand breaks. Radiation can cause chromosomes to break, stick together and rearrange. All these changes can lead to mutations or even further, the death of the cell. However, in addition to ionizing radiation, extracellular genotoxic chemicals and intracellular oxidative metabolic residues can also create stress in cells during DNA replication and cell division. Damage may occur during DNA replication under such environmental stress conditions. To date, conflicting results have been reported regarding the genotoxic effects of RF-EMF waves on genetic material. It has been reported that the energy of low EM fields is not sufficient to break the chemical bonds of DNA, but the increase in exposure time is effective on the formation of oxygen radicals and the disruptions in the DNA repair process. The absorption of microwaves can cause significant local warming in cells. For example, an increase in temperature has been observed in cells in culture media exposed to waves of high SAR levels. However, there is evidence that reactive oxygen species are formed in cells indirectly and experimentally exposed to RF-EMF waves. Free oxygen radicals can create nucleotide entries in DNA as well as bind cellular components to DNA bases (5). The frequency of polymorphisms observed in DNA repair mechanism genes in children with acute leukaemia living close to high energy lines reveals the effect of this energy on the repair process. Significant evidence has been reported that genotoxic effects occur in various cell types when exposed to RF-EMF waves (6-10). Here, it has been reported that cells exposed to RF-EMF waves (1.800 MHz, SAR 2 W/kg) cause oxidative damage in mitochondrial DNA, DNA breaks in neurons and DNA breaks in amniotic cells (6,10). Similarly, the damage has been reported in lymphocytes exposed to various RF-EMF waves (8). However, exposure to RF-EMF waves is known to cause chromosome imbalance, changes in gene expression, and gene mutations. Such deleterious genetic effects have also been reported in neurons, blood lymphocytes, sperm, red blood cells, epithelial cells, hematopoietic tissue, lung cells, and bone marrow (1,11,12). It has been found that exposure to RF-EMF radiation also increases chromosome numerical aberrations (6,13). It has also been reported that increased chromosome separation in mouse oocytes exposed to EM and increased DNA fragmentation and apoptosis in fly egg cells (14,15). However, increased DNA breaks have been reported in the blastomeres of embryos of pregnant mice exposed to a frequency of 50 Hz, and a decrease in the number of blastocysts has been reported (16). Genetic damages to sex cells can lead to persistent genetic diseases in subsequent generations. Today, X-ray devices used for medical diagnosis have become one of the largest sources of radiation. These radiological procedures used for diagnosis constitute an important part of ionizing radiation. During these processes, the human body is visibly or invisibly affected by X-rays. As a matter of fact, X-rays have effects of disrupting the structure and biochemical activities of DNA, RNA, proteins and enzymes that are vital in the organism (17). Many studies on this subject have revealed that radiation has suppressive and mutational effects on DNA synthesis. These effects can cause serious damage to the cell as well as DNA and chromosome damage. In a recent study, chromosome damage was investigated in patients with X-ray angiography and personnel working in radiological procedures (18). Our findings showed that the beams used in interventional radiological procedures caused chromosomal damage and the rate of chromosomal abnormalities (CAs) increased significantly in patients after the procedure and this damage increased with the amount of radiation dose. Therefore, the radiation dose to be given to the patient should be chosen carefully. Besides, our findings showed that the frequency of CA is significantly higher in personnel working in radiological procedures. This reveals that interventional cardiologists are exposed to high radiation exposure. For this reason, we can say that the personnel working in radiological procedures (physician, health technician and nurse) are very likely to get diseases after years because they are exposed to low doses but long-term X-rays. Therefore, both the potential risks and safety of exposure to medical radiological devices must be continuously monitored. Furthermore, the fact that chromatid and chromosome breaks are very common among structural CAs in our findings suggests that they may be the cause of malignancy. Because, there are many cancer genes, tumour suppressor genes, enzyme genes involved in DNA repair and important genes or candidate genes responsible forapoptosis on these chromosomes. All this information shows that patients are more susceptible to DNA damage and inappropriate radiological examinations should be avoided. Therefore, X-ray and other diagnostic imaging techniques should not be applied unless necessary, and physicians and patients should be more careful in this regard. It has been reported that RF-EMR waves emitted from wireless communication device mobile phones have a genotoxic effect on human and mammalian cells (6,19). In a recent study; The effects of 900 and 1800 MHz cell phone frequencies on human chromosomes were investigated in amniotic cell cultures (6). Here, it has been reported that chromosome packing delays, damage and breaks occur in amniotic cells exposed to 900 and 1800 MHz every day at 3, 6 and 12 hours for twelve days. However, it was found that the frequency of 1800 MHz caused more CAs than 900 MHz, and the amount of damage increased with increasing usage time. These results confirm that GSM-like RF-EMR causes direct genotoxic effects in human in vitro cultures and has adverse effects on human chromosomes, and these effects increase in parallel with exposure time. This shows us that the mobile phone carries a risk for human health and these genetic damages can cause cancer. Therefore, necessary precautions should be taken for these harmful effects of mobile phones. Among these measures, the periods of mobile phone use should be kept short, especially the exposure of developing children and infants to mobile phones should be prevented, and avoiding excessive use of mobile phones may be one of the precautions against cancer. However, in order to evaluate it in more detail, the effects of mobile phones with environmental mutagens and/or carcinogens should be considered in subsequent researches. ConclusionToday, in parallel with the increasing technological developments, the demand of the society for electronic devices and phones and the frequency ranges of electronic devices are constantly increasing. Waves emitted from electronic devices are absorbed by human and animal bodies. Especially, the use of phones by contact with our body and the increase in usage time affects not only adults but also young children. Therefore, there is increasing concern in society about the negative biological effects of EM waves emitted from phones and other electronic devices. Results from all studies show that RF-EMF waves may be carcinogenic due to their genotoxic effect. Because cancer is a disease that occurs as a result of genetic damage. Considering these negative and harmful effects, regulations following international standards regarding the use of electronic devices should be made and society should be made aware of the risks.References Kim JH.; Lee K.; Kim HG.; Kim KB.; Kim HR. 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Effects of ionizing radiation on DNA synthesis in eukaryotic cells. Int J Radiat Biol. 1999, 75( 3), 267-283. Çetinel N.; Demirhan O.; Demirtaş M.; Çağlıyan ÇE.; Cüreoğlu A.; Uslu IN.; Sertdemir Y. The Genotoxic Effect Of Interventional Cardiac Radiologic Procedures On Human Chromosomes. Clinical Medical Reviews and Reports. 2020, 3(1), 1-10. Aitken RJ.; Bennetts LE.; Sawyer D.; Wiklendt AM.; King BV. Impact of radio frequency electromagnetic radiation on DNA integrity in the male germline. Int J Androl. 2005, 28(3), 171–179.

Recent progress and future prospects in diagnostics of energetic electrons and ions in the flares are reviewed, together with the roles they play in the flare as a whole. Most of the discussion centres on hard X-ray and gamma-ray and thermal plasma emission data, rather than on radio sources. Since Solar Maximum Mission and Hinotori there has been major progress in all areas of flare electron diagnostics. Electron spectra are now recoverable with some precision, electrons with energies above 10 MeV are known to be highly anisotropic, and indications are available of the spatial distribution of electrons at 20 keV. Timescales of electron acceleration are now known to be shorter than 0.1 s. Energetic electrons are believed to carry much of the flare power. Ion diagnostics are more limited. For greater than 1 MeV ions the flux, spectrum and acceleration timescale are now quite well known. Low energy ions are hard to diagnose but have been invoked as a flare heating mechanism alternative to electron beams. The problems with beam heating models are discussed with special attention to the problems of the low energy proton model and its only direct diagnostic, Hα impact polarization. Finally, theoretical problems associated with return currents and with accelerator requirements are discussed and attention is drawn to the possible importance of entropy as well as energy considerations.

Propagation of radio emission in a pulsar magnetosphere is reviewed. The effects of polarization transfer, induced scattering and reprocessing to high energies are analysed with a special emphasis on the implications for the gamma-ray pulsars. The possibilities of the pulsar plasma diagnostics based on the observed radio pulse characteristics are also outlined. As an example, the plasma number density profiles obtained from the polarization data for the Vela and the gamma-ray millisecond pulsars J1446-4701, J1939+2134 and J1744-1134 are presented. The number densities derived tend to be the highest/lowest when the radio pulse leads/lags the gamma-ray peak. In the PSR J1939+2134, the plasma density profiles for the main pulse and interpulse appear to fit exactly the same curve, testifying to the origin of both radio components above the same magnetic pole and their propagation through the same plasma flow in opposite directions. The millisecond radio pulse components exhibiting flat position angle curves are suggested to result from the induced scattering of the main pulse by the same particles that generate gamma rays. This is believed to underlie the wide-sense radio/gamma-ray correlation in the millisecond pulsars. The radio quietness of young gamma-ray pulsars is attributed to resonant absorption, whereas the radio loudness to the radio beam escape through the periphery of the open field line tube.

Radioisotopes used for gamma-ray-based diagnostics have the main problem that imaging resolution quality.Gallium-68 is a positron (β+) emitting radioisotope that has better imaging resolution than gamma-based radioisotopes. Gallium-68 (68Ga) can be produced by irradiating natural gallium or zinc-68 enriched as a target with protons in an accelerator facility. Indonesia has planned to build a cyclotron type accelerator that operates in 13 MeV proton energy and 50 µA proton beam who has initials named DECY-13. Before it was commissioned for radioisotopes production purpose that was must conduct a preliminary study to determine 68Ga optimum irradiation time and properties, one of which was the monte carlo computation method using PHITS v3.24 software. Simulations were begun by irradiating proton with natural gallium target for 25 days with 2 days cooling and zinc-68 enriched for 120 minutes with cooling 10 minutes. The results at EOB of the long-lived process using the natGa target obtained total radioactivity of 189.42 MBq (5.12 mCi). The total radioactivity result of high activity process which used 68Zn enriched as a target was 268.6 GBq (7.259 Ci). the radioactivity was compared with another accelerator, that the long-lived process was too small and uneconomical to done, but the high activity process was feasible to produce. The results of this research expected will be considered as a feasibility study for the 68Ga production process in Indonesia in the future.

Abstract Alfvén eigenmode (AE) instabilities driven by alpha-particles have been observed in D-3He fusion experiments on the Joint European Torus (JET) with the ITER-like wall (ILW). For the efficient generation of fusion alpha-particles from D-3He fusion reaction, the 3-ion radio frequency (RF) scenario was used to accelerate the neutral beam injection 100-keV deuterons to higher energies in the core of mixed D-3He plasmas at high concentrations of 3He. A large variety of fast-ion driven magnetohydrodynamic (MHD) modes were observed, including the elliptical Alfvén eigenmodes (EAEs) with mode numbers n=-1 and axisymmetric modes with n=0 in the frequency range of EAEs. The simultaneous observation of these modes indicates the presence of rather strong alpha-particle population in the plasma with a “bump-on-tail” shaped velocity distribution. Linear stability analysis and Fokker Plank calculations support the observations.- Experimental evidence of the AEs excitation by fusion-born alpha-particles in the D-3He plasma is provided by neutron and gamma-ray diagnostics as well as fast-ion loss measurements. We discuss an experimental proposal for the planned full-scale D-T plasma experiments on JET based on the physics insights gained from these experiments.

The results of the photonuclear production of 11C and 18F isotopes in various target-matrices are summarized. The studies were performed using linear electron accelerators of the R&DE "Accelerator" NSC KIPT NAS of Ukraine in the energy range 10 -40 MeV to determine the possibilities of obtaining the maximum achievable activity levels of 11C isotopes, and 18F with a view to planning further developments on the creation of radiopharmaceutical for these nuclear isotopes. In the framework of the above approach, we measured the activity levels of the 18F which is transferred to the surrounding aquatic environment during irradiation of targets-matrices of fluoroplastic (C2F4) with bremsstrahlung flux. The release of the 18F isotope into the aquatic environment under the most favorable conditions (in terms of energy and average beam current) was 3.6% of the target-matrices activity - 40 MBq/g, which is a very low figure. Despite the encouraging value of the specific activity of 18F isotope in lithium fluoride (LiF) -77 MBq/g target–matrices and hydrofluoric acid (HF) - close to 100 MBq/g, the process of extracting 18F from C2F4, LiF and HF as basis of the radiopharmaceutical is not sufficiently effective and brings into question the feasibility of such a methodology for producing 18F isotope for further use. More efficient was the production of the 11C isotope in the irradiated target-matrix of the standard therapeutic form "glucose monohydrate" (glucose). It was shown that, as a result of irradiation of glucose with a gamma-quanta beam, it is possible to “label” glucose with the 11C isotope, which is formed as a result of the photonuclear reaction 12C(γ, n)11C at the 12C nucleus, which is part of the glucose molecule C6H12O6 ×H2O. Irradiated sample of glucose dissolved in a given volume of solvent (distilled water) will be ready for use radiopharmaceutical "Glucose, 11C". It has been shown that the “photonuclear method” provides for obtaining the “Glucose, 11C” radiopharmaceutical complex with total activity necessary for performing PET diagnostics. The radiopharmaceutical "Glucose, 11C" by the time of its use has 100% radionuclide purity. “Glucose, 11C” obtained in this way was produced for the first time. The choice of the optimal design of a water-cooled target station, providing a moderate (in terms of heat loads) mode of irradiation of a capsule filled with glucose tablets, is discussed. Using the program “SolidWorks FlowSimulation 2011”, the quantitative characteristics of the flow rates of water flowing around the glucose capsule and the converter are calculated.

Experiments performed on an inertial confinement fusion (ICF) platform offer a unique opportunity to study nuclear reactions, including reaction branches that are useful for diagnostic applications in ICF experiments as well as several that are relevant to nuclear astrophysics. In contrast to beam-accelerator experiments, experiments performed on an ICF platform occur over a short time scale and produce a plasma environment with physical parameters that are directly relevant to big bang and/or stellar nucleosynthesis. Several reactions of interest, such as D(T,γ)5He, H(D,γ)3He, H(T,γ)4He, and T(3He,γ)6Li produce high-energy gamma rays. S factors or branching ratios for these four reactions have recently been studied using various temporally-resolved Cherenkov detectors at the Omega laser facility. This work describes these detectors as well as the current standard technique for performing these measurements. Recent results for reactions D(T,γ)5He, H(D,γ)3He, H(T,γ)4He, and T(3He,γ)6Li are reviewed and compared to accelerator-based measurements. Limitations associated with implosion experiments and use of the current standard gamma detectors are discussed. A basic design for a gamma spectrometer for use at ICF facilities is briefly outlined.

Abstract Background and purpose To report on our clinical experience with a newly implemented workflow for radiotherapy (RT) emergency treatments, which allows for a fast treatment application outside the regular working-hours, and its clinical applicability. Methods Treatment planning of 18 emergency RT patients was carried out using diagnostic computed tomography (CT) without a dedicated RT simulation CT. The cone-beam CT (CBCT) deviations of the first RT treatment were analyzed regarding setup accuracy. Furthermore, feasibility of the “fast-track” workflow was evaluated with respect to dose deviations caused by different Hounsfield unit (HU) to relative electron density (rED) calibrations and RT treatment couch surface shapes via 3D gamma index analysis of exemplary treatment plans. The dosimetric uncertainty introduced by different CT calibrations was quantified. Results Mean patient setup vs. CBCT isocenter deviations were (0.49 ± 0.44) cm (x), (2.68 ± 1.63) cm (y) and (1.80 ± 1.06) cm (z) for lateral, longitudinal and vertical directions, respectively. Three out of four dose comparisons between the emergency RT plan calculated on the diagnostic CT and the same plan calculated on the treatment planning CT showed clinically acceptable gamma passing rates, when correcting for surface artifacts. The maximum difference of rED was 0.054, while most parts of the CT calibration curves coincided well. Conclusion In an emergency RT setting, the use of diagnostic CT data for treatment planning might be time-saving and was shown to be suitable for many cases, considering reproducibility of patient setup, accuracy of initial patient setup and accuracy of dose-calculation.

AbstractUltra-intense MeV photon and neutron beams are indispensable tools in many research fields such as nuclear, atomic and material science as well as in medical and biophysical applications. For applications in laboratory nuclear astrophysics, neutron fluxes in excess of 1021 n/(cm2 s) are required. Such ultra-high fluxes are unattainable with existing conventional reactor- and accelerator-based facilities. Currently discussed concepts for generating high-flux neutron beams are based on ultra-high power multi-petawatt lasers operating around 1023 W/cm2 intensities. Here, we present an efficient concept for generating γ and neutron beams based on enhanced production of direct laser-accelerated electrons in relativistic laser interactions with a long-scale near critical density plasma at 1019 W/cm2 intensity. Experimental insights in the laser-driven generation of ultra-intense, well-directed multi-MeV beams of photons more than 1012 ph/sr and an ultra-high intense neutron source with greater than 6 × 1010 neutrons per shot are presented. More than 1.4% laser-to-gamma conversion efficiency above 10 MeV and 0.05% laser-to-neutron conversion efficiency were recorded, already at moderate relativistic laser intensities and ps pulse duration. This approach promises a strong boost of the diagnostic potential of existing kJ PW laser systems used for Inertial Confinement Fusion (ICF) research.