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Background 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. Objective To systematically review literature on reintegration interventions for CPTSD, describing the nature and effectiveness of interventions. Method 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. Results 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. Conclusions 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., HIGHLIGHTS 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.

第35回宇宙環境利用シンポジウム(2021年1月19日-20日. オンライン開催), Space Utilization Research (January 19-20, 2021. Online Meeting), 資料番号: SA6000156020, レポート番号: G-12

第34回宇宙環境利用シンポジウム (2020年1月21日-22日. 宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS)), 相模原市, 神奈川県, Space Utilization Research (January 21-22, 2020. Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency(JAXA)(ISAS)), Sagamihara, Kanagawa Japan, 資料番号: SA6000145017, G-09

Purpose: To study the agreement between proton microdosimetric distributions measured with a silicon-based cylindrical microdosimeter and a previously published analytical microdosimetric model based on Geant4-DNA in-water Monte Carlo simulations for low energy proton beams. Methods and material: Distributions for lineal energy (y) are measured for four proton monoenergetic beams with nominal energies from 2.0 MeV to 4.5 MeV, with a tissue equivalent proportional counter (TEPC) and a silicon-based microdosimeter. The actual energy for protons traversing the silicon-based microdosimeter is simulated with SRIM. Monoenergetic beams with these energies are simulated with Geant4-DNA code by simulating a water cylinder site of dimensions equal to those of the microdosimeter. The microdosimeter response is calibrated by using the distribution peaks obtained from the TEPC. Analytical calculations for y‾F and y‾D using our methodology based on spherical sites are also performed choosing the equivalent sphere to be checked against experimental results. Results: Distributions for y at silicon are converted into tissue equivalent and compared to the Geant4-DNA simulated, yielding maximum deviations of 1.03% for y‾F and 1.17% for y‾D. Our analytical method generates maximum deviations of 1.29% and 3.33%, respectively, with respect to experimental results. Conclusion: Simulations in Geant4-DNA with ideal cylindrical sites in liquid water produce similar results to the measurements in an actual silicon-based cylindrical microdosimeter properly calibrated. The found agreement suggests the possibility to experimentally verify the calculated clinical y‾D with our analytical method. National Institute of Biomedical Imaging and Bioengineering 5P41 EB002033 European Union 745109, 675265 Gobierno de España RTI2018-098117-B-C21

A multi-element tissue-equivalent proportional counter (TEPC), based on a single gas electron multiplier (GEM) foil of standard geometry, has been constructed with 16 cylindrical sensitives volumes. In this article, the design of this novel counter is described and first microdosimetric measurements are presented. To study the response of the GEM-TEPC to both low and high linear energy transfer radiation fields, the microdosimetric spectra due to a 137Cs gamma-ray source and to fast neutrons from 7Li(d,n)8Be reaction have been measured using pure propane gas at low pressure, in order to simulate a tissue site of about 1 µm equivalent size. The comparison with spectra measured with a spherical TEPC and with a mini-TEPC demonstrates promising properties for application of the GEM-TEPC for microdosimetric applications.

第33回宇宙環境利用シンポジウム (2019年1月24日-25日. 宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS)), 相模原市, 神奈川県, Space Utilization Research (January 24-25, 2019. Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency(JAXA)(ISAS)), Sagamihara, Kanagawa Japan, 著者人数: 18名, 資料番号: SA6000132013, レポート番号: G-12

第32回宇宙環境利用シンポジウム (2018年1月15日-16日. 宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS)), 相模原市, 神奈川県, Space Utilization Research (January 15-16, 2018. Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency(JAXA)(ISAS)), Sagamihara, Kanagawa Japan, 著者人数: 16名, 資料番号: SA6000117018, レポート番号: G-13

International audience; This paper discusses an instrument intercomparison performed in the high-energy field at the CERF facility at CERN between 2015 and 2017 (October 2015, May 2016, November 2016 and June 2017). Measurements were performed in several reference exposure locations with the CERN extended-range Bonner Sphere Spectrometer (BSS), a Berthold LB4611, the LINUS rem counter from CERN, the LUPIN rem counter from ELSE Nuclear, the FHT 762 Wide Energy Neutron Detection Instrument (WENDI-II) from Thermo Scientific, the LUDLUM MODEL 42–41 PRESCILA NEUTRON PROBE and two models of Tissue-equivalent proportional counters (TEPCs) from Far West Technologies. All results are compared with the latest FLUKA reference values from simulations performed in 2017.

第31回宇宙環境利用シンポジウム (2017年1月16日-17日. 宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS)), 相模原市, 神奈川県, Space Utilization Research (January 16-17, 2017. Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency(JAXA)(ISAS)), Sagamihara, Kanagawa Japan, 著者人数: 16名, 資料番号: SA6000061032, レポート番号: SUS31-G17

第29回宇宙環境利用シンポジウム (2015年1月24日-25日. 宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS)), 相模原市, 神奈川県, Space Utilization Research (January 24-25, 2015. Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency(JAXA)(ISAS)), Sagamihara, Kanagawa Japan, 著者人数: 17名, 資料番号: SA6000035026, レポート番号: ISAS-SUR29-S21

In the past few years, miniaturized tissue-equivalent gas detectors (mini TEPCs) have been developed for application of microdosimetry in radiotherapy. These mini-TEPCs are characterised by millimetric dimensions. They are equipped neither with an internal calibration source nor with electric field tubes, which would properly define the sensitive volume hence the simulated site size. In spite of these lacks, mini TEPCs working in gas flow conditions have proven to be precise and reliable detectors. However, for future therapeutic plans including microdosimetric data, consistency between experimental and calculated data is important. Existing general-purpose Monte Carlo codes have proven to be very useful to calculate the energy deposition due to ionization in macroscopic targets, even in various complex radiation fields. However, theoretical models implemented in these codes for simulating electron transport and straggling are valid only for energies above a few keV. This restricts their applicability for simulating radiation transport at a micrometric level, where low-energy electrons play a dominant role. In this work, we calculate frequency distributions of deposited energy in a mini TEPC (with sizes equivalent to 1 and 2 μm) due to photons using the Monte Carlo code FLUKA. Comparisons between simulated and experimental data show a rather good agreement. Differences due to different FLUKA settings are discussed.

The BNCT radiation field is complex because different beam components are mixed, each one having different relative biological effectiveness (RBE). Microdosimetry with tissue-equivalent proportional counters (TEPC) has proven to be an ideal dosimetric technique for mixed radiation fields, because it is able both to measure the absorbed dose and to assess the radiation field relative biological effectiveness with good accuracy. An ideal detector for BNCT should contain two TEPCs, one detector loaded with, while the other one without (10)B in order to record all beam components with a unique measurement. Moreover, such a detector should be of tiny size in order to be able to measure in the intense BNCT radiation fields without significant pile-up effects. TEPCs have been shown to be pretty good dosimeters for mixed radiation fields. In this paper the first mini twin TEPC counter for BNCT is presented, as well as first measurement at the new HYTHOR thermal irradiation facility at TAPIRO nuclear reactor and comparison with related Monte Carlo calculations.

第30回宇宙環境利用シンポジウム (2016年1月19日-20日. 宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS)), 相模原市, 神奈川県, Space Utilization Research (January 19-20, 2016. Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency(JAXA)(ISAS)), Sagamihara, Kanagawa Japan, 著者人数: 15名, 資料番号: SA6000048009, レポート番号: G-05

A tissue-equivalent proportional counter (TEPC) simulates micrometric volumes of tissue if the energy deposited in the counter cavity is the same as that in the tissue volume. Nevertheless, a TEPC measures only the ionisations created in the gas, which are later converted into imparted energy. Therefore, the equivalence of the simulated diameter (Dρ) in two gases should be based on the equality of the mean number of ions pairs in the gas rather than on the imparted energy. Propane-based tissue-equivalent gas is the most commonly used gas mixture at present, but it has the drawback that its composition may change with time. From this point of view, the use of pure propane offers practical advantages: higher gas gain and longer stability. In this work, microdosimetric measurements performed with pure propane, at site sizes 0.05 mg cm(-2) ≤ Dρ ≤ 0.3 mg cm(-2), demonstrate that the response of a propane-filled detector in gamma and in neutron fields is almost the same if an appropriate gas density is used.

Proton beams (62 Mev) are used by the Laboratori Nazionali del Sud of the Italian Institute of Nuclear Physics to treat eye melanoma tumours at the therapeutic facility called CATANA. A cylindrical slim tissue-equivalent proportional counter (TEPC) of 2.7 mm external diameter has been used to compare the radiation quality of two spread-out Bragg peaks (SOBP) at the CATANA proton beam.

第28回宇宙利用シンポジウム (2012年1月23-24日. 日本学術会議), 港区, 東京都, Space Utilization Research (January 23-24, 2012. Science Council of Japan), Minato-ku, Tokyo Japan, 著者人数: 17名, 資料番号: SA6000032043, レポート番号: L03

The thymus is the major site for T-cell generation and thus is important for the adaptive immune system. Development of a properly selected, functional T-cell repertoire relies on interactions between developing T cells and a series of functionally distinct thymic stroma cell types including the cortical and medullary thymic epithelial cells (TECs). The thymus is one of the first organs to degenerate in normal healthy ageing. Related to this, there is strong interest in developing protocols for improving thymus function in patients by cell replacement or regenerative therapies. Thymic epithelial progenitor cells (TEPCs) represent a potential source of cells for thymus transplantation. However, the only source of these cells for transplantation is currently fetal thymus tissue. If TEPCs could be generated from pluripotent cells, this could provide an alternative source of cells for transplantation. The work described in this thesis therefore had two central aims (i) to test the stability of thymic epithelial progenitor cells in vivo and (ii) to investigate the possibility of generating TEPCs or TECs from mouse embryonic stem (ES) cells. The forkhead transcription factor, Foxn1, is essential for the development of a functionally mature thymic epithelium, but is not necessary for formation of the thymic primordium or for medullary thymic epithelial sub-lineage specification. By reactivating Foxn1 expression postnatally in mice carrying a revertible hypomorphic allele of Foxn1, Foxn1R, I herein demonstrate that TEPCs that can express only low levels of Foxn1 mRNA can persist postnatally in the thymic rudiment in mice until at least 6 months of age, and retain the potential to give rise to both cortical and medullary thymic epithelial cells (cTECs and mTECs). These data demonstrate that the TEPC-state is remarkably stable in vivo under conditions of low Foxn1 expression. In parallel with this work, I confirmed the possibility of generating Foxn1-expressing cells from mouse ES cells by using a Foxn1 reporter cell line. As the thymic epithelium has a single origin in the third pharyngeal pouch (3pp) endoderm, I then tested whether or not TEPCs and /or TECs were generated during ES cell differentiation via existing protocols for generating anterior definitive endoderm differentiation cells from mouse ES cells. From this work, I showed that genes expressed in the 3pp and/or TEPC,-including Plet-1, Tbx1, Hoxa3 and Pax9, were induced by differentiation of ES cells using these protocols. I further showed that cells expressing both Plet-1, a marker of foregut endoderm and 3pp, and EpCAM, a marker of proliferating epithelial cells, were induced using a novel protocol (2i ADE) for generating ES cells from ADE. However, gene expression analysis and functional testing suggested that the majority of these cells were non-thymus lineage. I subsequently developed a novel protocol which combined this 2i ADE protocol with co-culturing of the differentiating ES cells with fetal thymic lobes, and demonstrated that this further induced 3pp and TEPC related genes. Finally, I modified the culture conditions in this protocol to conditions predicted to better support TEPC/TEC, and showed that in these conditions, the TEPC-specific markers Foxn1 and IL-7 were induced more strongly than in any other conditions tested. The data presented in this thesis therefore represent an advance towards an optimized protocol for successfully generating TEPCs from ES cells in vitro.

In 2007, the European Space Agency (ESA) initiated the development of European Crew Personal Active Dosimeters. The hardware development objective is to produce an active personal dosimeter which shows absorbed dose and dose equivalent spectra similar to a Tissue Equivalent Proportional Counter (TEPC), but which is based on more robust silicon detector devices. Several detector/dosimeter components have been investigated – by computer simulations – for their performance in the radiation field at the ISS position.

In the framework of an advanced Exotic Ion Beam facility, named SPES (Study and Production of Exotic Species), that will allow a frontier program both in nuclear and interdisciplinary physics, an intense thermal neutron beam facility, devoted to perform Boron Neutron Capture Therapy (BNCT) experimental treatments on skin melanoma tumor, is currently under construction based on the SPES proton driver. A vast radiobiological investigation in vitro and in vivo has started with the new 10B carriers developed. Special microdosimetric detectors have been constructed to properly measure all the BNCT dose components and their qualities. Both microdosimetric and radiobiological measurements are being performed at the new HYTHOR beam shaping assembly at the Enea‐Casaccia TAPIRO reactor.

A new type of mini multi-element tissue-equivalent proportional counter (TEPC) based on a gas electron multiplier (GEM) has been designed and constructed. This counter is in particular suitable to be constructed with a small sensitive volume so that it can be used for microdosimetry in intense pulsed radiation fields to measure the microdosimetric spectrum in the beam of, for instance, a clinical linear accelerator. The concept lends itself also for a mini multi-element version of the counter to be used for applications in which a high sensitivity is required. In this paper, we present the first microdosimetric measurements of this novel counter exposed to a 14 MeV monoenergetic neutron beam and a californium (252Cf) source for a counter cavity diameter of 1.8 mm simulating 1.0 microm tissue site size. The measured spectra showed an excellent agreement with spectra from the literature. The specific advantages of the TEPC-GEM are discussed.

Ionising radiation causes a wide variety of effects in biological targets. In experimental microdosimetry these effects are studied by investigating the statistical distribution of energy deposition events at the microscopic level employing a Tissue-Equivalent Proportional Counter (TEPC). A TEPC is usually designed with a cavity of a few centimetres in diameter containing a central anode wire and operated with a tissue-equivalent wall and counting gas at low pressure to simulate tissue volumes of micrometer dimensions. However, in experimental microdosimetry there are some conditions such as high flux therapy beams and energy deposition on nanometer level (nanodosimetry) in which TEPCs with very small cavities are needed. The construction of a central wire in a small cavity is extremely difficult and expensive. It becomes even more difficult when multi-element cavities are applied to increase the counter sensitivity. Therefore, a new type of TEPC was developed based on a Gas Electron Multiplier (GEM). The design and construction of a TEPC-GEM is described. The successful operation of this counter has been shown by the first microdosimetric measurements of the TEPC-GEM exposed to a 14 MeV monoenergetic neutron beam and a californium (252Cf) source for a cavity diameter of 1.8 mm, simulating a 1.0 μm tissue site size. The measured spectra show an excellent agreement with spectra from the literature. Furthermore, the first microdosimetric responses for low energy X-rays are presented for counter cavities of 1.8 mm, 1.0 mm and 0.5 mm diameter at various pressures, simulating tissue site sizes down to 140 nm. This new design not only simplifies the construction of mini multi-element counters but it also facilitates microdosimetry measurements (e.g. in nanodosimetry, personal dosimetry and space dosimetry) in a relatively easy manner. Because of the relatively simple design and construction, the TEPC-GEM is not only relatively cheap and easy to produce but also its components (sensitive volume, GEM and wall materials) can be modified and adapted to the needs. In general, it can be concluded that this small counter cavity opens new possibilities in application for high intensity radiation fields as well as in nanodosimetry. Furthermore, its robust and multi-element concept makes it suitable for applications in space and aviation.

Ionising radiation causes a wide variety of effects in biological targets. In experimental microdosimetry these effects are studied by investigating the statistical distribution of energy deposition events at the microscopic level employing a Tissue-Equivalent Proportional Counter (TEPC). A TEPC is usually designed with a cavity of a few centimetres in diameter containing a central anode wire and operated with a tissue-equivalent wall and counting gas at low pressure to simulate tissue volumes of micrometer dimensions. However, in experimental microdosimetry there are some conditions such as high flux therapy beams and energy deposition on nanometer level (nanodosimetry) in which TEPCs with very small cavities are needed. The construction of a central wire in a small cavity is extremely difficult and expensive. It becomes even more difficult when multi-element cavities are applied to increase the counter sensitivity. Therefore, a new type of TEPC was developed based on a Gas Electron Multiplier (GEM). The design and construction of a TEPC-GEM is described. The successful operation of this counter has been shown by the first microdosimetric measurements of the TEPC-GEM exposed to a 14 MeV monoenergetic neutron beam and a californium (252Cf) source for a cavity diameter of 1.8 mm, simulating a 1.0 μm tissue site size. The measured spectra show an excellent agreement with spectra from the literature. Furthermore, the first microdosimetric responses for low energy X-rays are presented for counter cavities of 1.8 mm, 1.0 mm and 0.5 mm diameter at various pressures, simulating tissue site sizes down to 140 nm. This new design not only simplifies the construction of mini multi-element counters but it also facilitates microdosimetry measurements (e.g. in nanodosimetry, personal dosimetry and space dosimetry) in a relatively easy manner. Because of the relatively simple design and construction, the TEPC-GEM is not only relatively cheap and easy to produce but also its components (sensitive volume, GEM and wall materials) can be modified and adapted to the needs. In general, it can be concluded that this small counter cavity opens new possibilities in application for high intensity radiation fields as well as in nanodosimetry. Furthermore, its robust and multi-element concept makes it suitable for applications in space and aviation.

A mini-tissue-equivalent proportional-counter (TEPC) has been constructed to study the possibility to manufacture mini-counters without field-shaping tubes for radiation therapy. The mini-TEPC can be assembled with and without field-shaping tubes. It can be equipped with a mini-alpha source for a precise lineal energy calibration. After the positive conclusions of this study, a slim TEPC has been designed and constructed. The slim TEPC has an external diameter of only 2.7 mm. It has been tested with therapeutic proton beams and gamma ray sources.

A thermal column is available for dosimetric and radiobiological studies by the fast reactor TAPIRO, located at the ENEA research centre Casaccia. The TAPIRO neutron field has been studied (in the frame of LNL BNCT project) with a tissue-equivalent proportional counter, which has worked alternatively with an ordinary tissue-equivalent cathode and with a boron-enriched cathode. Measurements have been performed with polyethylene caps of different thickness. Both the absorbed dose and the microdosimetric-calculated biological effective dose show a maximum at approximately 0.5 mg cm(-2) of depth. The different dose components have been calculated and the results are discussed.

By employing a Gas Electron Multiplier a new type of mini multi-element Tissue-Equivalent Proportional Counter (TEPC) has been designed and constructed. In this paper, we describe the design of this novel counter. The first pulse height measurements with this counter for both methane- and propane-based Tissue Equivalent gases are presented. These results show promising properties for application of this novel type TEPC in microdosimetric measurements.

This paper illustrates a tissue-equivalent proportional counter designed to have high gas gain and good energy resolution at nanometric simulated site sizes. Microdosimetric neutron and gamma spectra were measured in dimethyl ether and in propane-based tissue-equivalent gas mixture down to 35 nm. The comparison of experimental data with the results of Monte Carlo calculations shows a satisfactory agreement.