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The interest in hadron therapy is growing fast thanks to the latest technological advances in accelerators and delivery technologies, to the development of more and more efficient and comprehensive treatment planning tools, and due to its increasing clinical adoption proving its efficacy. A precise and reliable beam quality assessment and an accurate and effective inclusion of the biological effectiveness of different radiation qualities are fundamental to exploit at best its advantages with respect to conventional radiotherapy. Currently, in clinical practice, the quality assurance (QA) is carried out by means of conventional dosimetry, while the biological effectiveness of the radiation is taken into account considering the Relative Biological Effectiveness (RBE). The RBE is considered a constant value for protons and it is estimated as a function of the absorbed dose in case of carbon ions. In this framework, microdosimetry could bring a significant improvement to both QA and RBE estimation. By measuring the energy deposited by the radiation into cellular or sub-cellular volumes, microdosimetry could provide a unique characterisation of the beam quality on one hand, and a direct link to radiobiology on the other. Different detectors have been developed for microdosimetry, from the more conventional tissue equivalent proportional counter (TEPC), silicon-based and diamond-based solid-state detectors, to ΔE-E telescope detectors, gas electrons multiplier (GEM), hybrid microdosimeters and a micro-bolometer based on Superconducting QUantum Interference Device (SQUID) technology. However, because of their different advantages and drawbacks, a standard device and an accredited experimental methodology have not been unequivocally identified yet. The establishment of accepted microdosimetry standard protocols and code of practice is needed before the technique could be employed in clinical practice. Hoping to help creating a solid ground on which future research, development and collaborations could be planned and inspired, a comprehensive state of the art of the detector technologies developed for microdosimetry is presented in this review, discussing their use in clinical hadron therapy conditions and considering their advantages and drawbacks.

Measurements in the stray radiation field from a proton therapy pencil beam at energies 70 and 146 MeV were performed using microdosimetric tissueequivalent proportional counters (TEPCs). The detector volumes were filled with a propane-based tissue-equivalent gas at low pressure simulating a mean chord length of 2 mmin tissue. Investigations were performed with and without a beam range shifter, and with different air gaps between the range shifter and a solid water phantom. The absorbed dose, the dose-mean lineal energy, and the dose equivalent were determined for different detector positions using the variance-covariance method. The influence from beam energy, detector- and range-shifter positions on absorbed dose, LET, and dose equivalent were investigated. Monte Carlo simulations of the fluence, detector response, and absorbed dose contribution from different particles were performed with MCNP 6.2. The simulated dose response for protons, neutrons, and photons were compared with, and showed good agreement with, previously published experimental data. The simulations also showed that the TEPC absorbed dose agrees well with the ambient absorbed dose for neutron energies above 20 MeV. The results illustrate that changes in both dose and LET variations in the stray radiation field can be identified from TEPC measurements using the variance-covariance method. The results are in line with the changes seen in the simulated relative dose contributions from different particles associated with different proton energies and range-shifter settings. It is shown that the proton contribution scattered directly from the range shifter dominates in some situations, and although the LET of the radiation is decreased, the ambient dose equivalent is increased up to a factor of 3. [ABSTRACT FROM AUTHOR]

Measurements in the stray radiation field from a proton therapy pencil beam at energies 70 and 146 MeV were performed using microdosimetric tissue-equivalent proportional counters (TEPCs). The detector volumes were filled with a propane-based tissue-equivalent gas at low pressure simulating a mean chord length of 2 μm in tissue. Investigations were performed with and without a beam range shifter, and with different air gaps between the range shifter and a solid water phantom. The absorbed dose, the dose-mean lineal energy, and the dose equivalent were determined for different detector positions using the variance–covariance method. The influence from beam energy, detector- and range-shifter positions on absorbed dose, LET, and dose equivalent were investigated. Monte Carlo simulations of the fluence, detector response, and absorbed dose contribution from different particles were performed with MCNP 6.2. The simulated dose response for protons, neutrons, and photons were compared with, and showed good agreement with, previously published experimental data. The simulations also showed that the TEPC absorbed dose agrees well with the ambient absorbed dose for neutron energies above 20 MeV. The results illustrate that changes in both dose and LET variations in the stray radiation field can be identified from TEPC measurements using the variance–covariance method. The results are in line with the changes seen in the simulated relative dose contributions from different particles associated with different proton energies and range-shifter settings. It is shown that the proton contribution scattered directly from the range shifter dominates in some situations, and although the LET of the radiation is decreased, the ambient dose equivalent is increased up to a factor of 3.

Abstract Ionizing radiation at aircraft and commercial suborbital spaceflight altitudes is driven by space weather and is a health concern for crew and passengers. We compare the response functions of two radiation detectors that were exposed to four different ground‐based laboratory radiation fields as well as flown alongside each other on aircraft. The detectors were a tissue equivalent proportional counter (TEPC) and a Teledyne silicon micro dosimeter chip that was integrated into an Automated Radiation Measurements for Aerospace Safety Flight Module (ARMAS FM). Both detectors were flown onboard commercial and research aircraft. In addition, both detectors were exposed neutrons at the Los Alamos Neutron Science Center, protons at Loma Linda University Medical Center, 56Fe particles at the NASA Space Radiation Laboratory, and also a gamma radiation source at Lawrence Livermore National Laboratory. The response of each of these instruments as well as derived dosimetric quantities are compared for each radiation exposure and the ratio for converting ARMAS absorbed dose in silicon to an estimated absorbed dose in tissue is obtained. This process resulted in the first definitive calibration of the silicon‐based detector like ARMAS to TEPC. In particular, with seven flights of both instruments together, the ARMAS‐derived dose in tissue was then validated with the TEPC‐measured dose in tissue and these results are reported. This work provides a method for significantly improving the accuracy of radiation measurements relevant to human tissue safety using a silicon detector that is easy to deploy and can report data in real time.

Clinical guidelines recommend a phase-based approach to treatment for complex post-traumatic stress disorder (CPTSD), yet little is known about what interventions are being offered and which may be effective in the final 'reintegration' phase. To systematically review literature on reintegration interventions for CPTSD, describing the nature and effectiveness of interventions. We searched four electronic databases (Medline, PsycINFO, Embase, and PTSDpubs) for interventions aiming to facilitate reintegration for participants with probable CPTSD. We had two aims: firstly, to describe the interventions and secondly, to describe their effectiveness as measured through measures of reintegration, PTSD and/or disturbances in self-organization (DSO), or qualitative data describing changes experienced. Results are presented using narrative synthesis. Fifteen studies met our inclusion criteria. Interventions included yoga, exercise, use of service dogs, residential treatment, education, self-defence and patient research involvement. Overall study quality was low, as assessed by critical appraisal tools. Of the six studies including a control group, two reported a statistically significant improvement in the measure of reintegration between the intervention and control group, four studies reported a statistically significant difference in the measure of PTSD symptoms, but none reported any significant differences between intervention and control groups in DSO. Of all eight quantitative studies, three reported a statistically significant difference in the reintegration measure pre- to post-intervention for the intervention group, five a statistically significant improvement in the measure of PTSD symptoms, and three a significant difference in the DSO measure. From eight studies reporting qualitative date we synthesized themes into eight categories, within which facilitation of connection with others was the most commonly reported benefit. The interventions outlined may facilitate reintegration, however, research in this area is still in its infancy and quality research is lacking. Further research is needed to establish whether reintegration interventions enhance treatment for CPTSD. A phased-based approach to treating CPTSD has been recommended by experts; however Phase 3 'Reintegration' interventions have been subject to little research. This review showed such interventions may reduce CPTSD symptoms and enhance integration, but research evidence is currently weak. [ABSTRACT FROM AUTHOR]

Tissue equivalent proportional counter (TEPC) is used to measure the micro-dose spectrum of ionizing radiation. Through changing tissue-equivalent gas pressure, TEPC can simulate the case of radiation energy deposition in different sizes of human cells. Various dosimetric quantities can be obtained such as absorbed dose, radiation quality factor and micro-dose equivalent. Because TEPC simulated cell size is less than the range of ionizing radiation particles, TEPC can be used as linear energy transfer spectroscopy, which can identify different linear energy transfer particles in a mixed radiation field and play an important role in mixed neutron–photon radiation field monitoring and protection. A tissue equivalent proportional counter is designed and manufactured in this paper. Through the built of micro-dose detector signal testing platform, and the realization of measurement of micro-dose detector signal debugging and important parameters (stability, energy resolution, etc.) by α source method, micro-dose energy spectrum analysis and experimental measurements of Cf-252 source were ultimately achieved. Results show that the detector has good sealing performance and stability, with 12 h stability better than 2.7%. Based on all the above spectra, micro-dosing spectrum of Cf-252 source was experimentally obtained. [ABSTRACT FROM AUTHOR]

Single ventricle heart defects (SVDs) are congenital disorders that result in a variety of complications, including increased ventricular mechanical strain and mixing of oxygenated and deoxygenated blood, leading to heart failure without surgical intervention. Corrective surgery for SVDs are traditionally handled by the Fontan procedure, requiring a vascular conduit for completion. Although effective, current conduits are limited by their inability to aid in pumping blood into the pulmonary circulation. In this report, we propose an innovative and versatile design strategy for a tissue engineered pulsatile conduit (TEPC) to aid circulation through the pulmonary system by producing contractile force. Several design strategies were tested for production of a functional TEPC. Ultimately, we found that porcine extracellular matrix (ECM)-based engineered heart tissue (EHT) composed of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and primary cardiac fibroblasts (HCF) wrapped around decellularized human umbilical artery (HUA) made an efficacious basal TEPC. Importantly, the TEPCs showed effective electrical and mechanical function. Initial pressure readings from our TEPC in vitro (0.68 mmHg) displayed efficient electrical conductivity enabling them to follow electrical pacing up to a 2 Hz frequency. This work represents a proof of principle study for our current TEPC design strategy. Refinement and optimization of this promising TEPC design will lay the groundwork for testing the construct's therapeutic potential in the future. Together this work represents a progressive step toward developing an improved treatment for SVD patients. Single Ventricle Cardiac defects (SVD) are a form of congenital disorder with a morbid prognosis without surgical intervention. These patients are treated through the Fontan procedure which requires vascular conduits to complete. Fontan conduits have been traditionally made from stable or biodegradable materials with no pumping activity. Here, we propose a tissue engineered pulsatile conduit (TEPC) for use in Fontan circulation to alleviate excess strain in SVD patients. In contrast to previous strategies for making a pulsatile Fontan conduit, we employ a modular design strategy that allows for the optimization of each component individually to make a standalone tissue. This work sets the foundation for an in vitro , trainable human induced pluripotent stem cell based TEPC. Image, graphical abstract [ABSTRACT FROM AUTHOR]

During high altitude long haul flights pilots, cabin crew and passengers are exposed to enhanced level of radiation originating from cosmic ray showers (CRS), produced via the interaction of very high-energy (~GeV) primary protons with the air molecules in Earth's atmosphere. The CRS are composed of energetic particles of diverse species, i.e. neutrons, protons, electrons, muons, pions and photons. Furthermore, the magnitude of aircrew radiation exposure depends on flight altitude and duration, geographical location (latitude), geomagnetic conditions and solar activity (modulation) status. In 1990 the International Commission on Radiological Protection (ICRP) classified airline crewmembers as "radiation workers". A miniature passive microdosimeter (LiBe-14) based on LiF (TLD700) and Beryllium Oxide (BeO) thermoluminescence dosimeter chips emulating a large volume gas-filled Tissue Equivalent Proportional Counter (TEPC) was developed by one of the authors (BM). The LiBe-14 was deployed to assess the integrated ambient dose equivalent of two commercial pilots on long haul intercontinental flights during March–May 2017. The accumulated dose equivalents of 1st (38 y, Female, 148 total block hours) and 2nd (29 y, Male, 149 total block hours) pilots were evaluated to be 565 μSv ± 105 μSv and 738 μSv ± 137 μSv, respectively. The results agreed well within ±20% of simulated data evaluated using the well-known EPCARD (E uropean P rogram Package for the C alculation of A viation R oute D oses) aviation dosimetry code. The implementation of LiBe-14 Microdosimeter in routine long haul, high-altitude commercial flights for the estimation of dose equivalent, average LET and quality factor relevant to impinging cosmic radiation is recommended. • Microdosimeter (LiBe) based on LiF and BeO TLD. • Polystyrene phantom bombarded with 81- 231 MeV protons. • TLD cross calibration using a gas-filled TEPC. • Dose Equivalent, Average LET, Quality Factor. • LiBe-Microdosimeter used in aircrew dosimetry. [ABSTRACT FROM AUTHOR]

Highlights: [•] ISSCREM is able to predict measured TEPC dose equivalent values at the Zvezda Service Module panel 327 (SM-327). [•] Measured dose equivalent from GCR and trapped radiation sources are predicted to within 10% and 20%, respectively. [•] Trapped radiation dose equivalent is dependent on TEPC location and orientation but GCR component varies minimally. [ABSTRACT FROM AUTHOR]

Abstract: A rapid analytical procedure for the prediction of a micro-dosimeter response function in low Earth orbit (LEO), correlated with the Space Transportation System (STS, shuttle) Tissue Equivalent Proportional Counter (TEPC) measurements is presented. The analytical model takes into consideration the energy loss straggling and chord length distribution of the detector, and is capable of predicting energy deposition fluctuations in a cylindrical micro-volume of arbitrary aspect ratio (height/diameter) by incoming ions through both direct and indirect (δ ray) events. At any designated (ray traced) target point within the vehicle, the model accepts the differential flux spectrum of Galactic Cosmic Rays (GCRs) and/or trapped protons at LEO as input. On a desktop PC, the response function of TEPC for each ion in the GCR/trapped field is computed at the average rate of 30s/ion. The ionizing radiation environment at LEO is represented by O’Neill’s GCR model (2004), covering charged particles in the 1⩽ Z ⩽28 range. O’Neill’s free space GCR model is coupled with the Langley Research Center (LaRC) angular dependent geomagnetic cutoff model to compute the transmission coefficient in LEO. The trapped proton environment is represented by a LaRC developed time dependent procedure which couples the AP8MIN/AP8MAX, Deep River Neutron Monitor (DRNM) and F10.7 solar radio frequency measurements. The albedo neutron environment is represented by the extrapolation of the Atmospheric Ionizing Radiation (AIR) measurements. The charged particle transport calculations correlated with STS 51 and 114 flights are accomplished by using the most recent version (2005) of the LaRC deterministic High charge (Z) and Energy TRaNsport (HZETRN) code. We present the correlations between the TEPC model predictions (response function) and TEPC measured differential/integral spectra in the lineal energy (y) domain for both GCR and trapped protons, with the conclusion that the model correctly accounts for the increase in flux at low y values where energetic ions are the primary contributor. We further discuss that, even with the incorporation of angular dependency in the cutoffs, comparison of the GCR differential/integral flux between STS 51 and 114 TEPC measured data and current calculations indicates that there still exists an underestimation by the simulations at low to mid range y values. This underestimation is partly related the exclusion of the secondary pion particle production from the current version of HZETRN. [Copyright &y& Elsevier]

Abstract: The radiation impact to astronauts depends strongly on the particles’ linear energy transfer (LET) and is dominated by high LET radiation. It is important to investigate the LET spectrum for the radiation field in low Earth orbit (LEO) and the influence of radiation on astronauts. The best active dosimeter used for all LET is the tissue equivalent proportional counter (TEPC); the best passive dosimeter used for high LET is CR-39 plastic nuclear track dosimeters (PNTDs). TEPC and CR-39 PNTDs were used to investigate the radiation in LEO. LET spectra and radiation quantities were obtained for STS-112 and STS-114 missions with TEPC and CR-39 PNTDs. This paper introduces the operation principles for the two types of dosimeters, presents radiation results measured and compares the results obtained with different dosimeters. [Copyright &y& Elsevier]

Abstract: The Sun goes through cycles of high and low activity that repeats approximately every 11 years. The solar activity is correlated to the number of dark spots on the Sun which are sources of sudden, sporadic eruptions, releasing energetic particles into space. This can directly affect the ionosphere and radio communications around the Earth. A spectacular and unusually high sunspot activity occurred during October and November 2003, commonly referred to as the Halloween Storms. The increased radiation exposure at aircraft altitudes during such an event is of major concern to international aviation organizations, airlines, governmental authorities and aircraft crew as well as flight passengers. Here, we report radiation exposure measurements made by ARC Seibersdorf research (ARCS) onboard commercial aircraft using a tissue equivalent proportional counter (TEPC). A unique set of long-term measurements was collected before, during and after the storm at flight altitudes. The results of these investigations give an understanding of the combined effects of magnetic field disturbances and solar particle fluence due to a solar storm, showing a 70% variation in the radiation exposure at typical flight altitudes. Whilst several predictive codes exist the radiation exposure to aircrew during a solar storm is difficult to predict by calculation models. These calculation models are still struggling with the high uncertainty of spectral input data provided by satellites during a solar storm. A reliable dose assessment concept to assess the radiation exposure to aircrew caused by a solar storm using a network of dosimeter instruments on-board several aircraft can be achieved. Such a proposal has been already introduced by experts of the European Radiation Dosimetry Group (EURADOS). [Copyright &y& Elsevier]