Boron neutron capture therapy (BNCT) is a high-dose-intensive radiation therapy that has gained popularity due to advancements in accelerator neutron sources. To determine the dose for BNCT, it is ...necessary to know the difficult-to-determine boron concentration and neutron fluence. To estimate this dose, we propose a method of measuring the prompt γ-rays (PGs) from the boron neutron capture reaction (BNCR) using a Compton camera. We performed a fundamental experiment to verify basic imaging performance and the ability to discern the PGs from 511 keV annihilation γ-rays. A Si/CdTe Compton camera was used to image the BNCR and showed an energy peak of 478 keV PGs, separate from the annihilation γ-ray peak. The Compton camera could visualize the boron target with low neutron intensity and high boron concentration. This study experimentally confirms the ability of Si/CdTe Compton cameras to image BNCRs.
The bias correction of the General Circulation Model (GCM) outputs has become a routine step that is taken in climate change impact assessments. To responsibly support the decision‐making processes, ...the climate‐modeling community has been debating about the conceptual requirements that bias‐correction methods should fulfill. Bearing in mind these requirements, we propose to decompose atmospheric variables into three temporal elements that represent the climate mean state, the interannual variability, and the daily variability. This decomposition is aimed at correcting the biases at one time scale without affecting the simulated climate (mean state) trend or the distributional properties at other time scales. The novelty of the proposed approach is, nevertheless, marked by the adjustment of interannual and daily variability that is made by replacing the GCM‐simulated data with synthetic samples drawn from Stable Distributions (SDs) that are fitted to the observed variability. The replacement prevents the transfer of the sampling variability of the calibration period and gives the corrected data the distributional properties of the observed climate. The employment of SDs was motivated by the fact that the climate‐change‐induced changes in the scale, the symmetry, and the frequency of extremes can be measured and applied to the SDs of the observed data. We correct the biases in the GCM‐simulated temperature and precipitation over northern South America using our proposed approach and two other existing ones. Our proposed method is capable of not only preserving the simulated climate trends but also reproducing the observed extremes as well as a more flexible method based on nonparametric distributions.
Key Points
We decompose GCM's daily time series into terms that represent the climate mean state, the interannual variability, and the daily variability
We replace the modeled daily variability using trend‐preserving synthetic samples that are drawn from stable distributions
The mathematical properties of stable distributions allow the inclusion of simulated climate change in the correction process
A project team headed by University of Tsukuba launched the development of a new accelerator based BNCT facility. In the project, we have adopted Radio-Frequency Quadrupole (RFQ)+Drift Tube Linac ...(DTL) type linac as proton accelerators. Proton energy generated from the linac was set to 8MeV and average current was 10mA. The linac tube has been constructed by Mitsubishi Heavy Industry Co. For neutron generator device, beryllium is selected as neutron target material; high intensity neutrons are generated by the reaction with beryllium and the 80kW proton beam.
Our team chose beryllium as the neutron target material. At present beryllium target system is being designed with Monte-Carlo estimations and heat analysis with ANSYS. The neutron generator consists of moderator, collimator and shielding. It is being designed together with the beryllium target system. We also acquired a building in Tokai village; the building has been renovated for use as BNCT treatment facility. It is noteworthy that the linac tube had been installed in the facility in September 2012.
In BNCT procedure, several medical devices are required for BNCT treatment such as treatment planning system, patient positioning device and radiation monitors. Thus these are being developed together with the linac based neutron source. For treatment planning system, we are now developing a new multi-modal Monte-Carlo treatment planning system based on JCDS. The system allows us to perform dose estimation for BNCT as well as particle radiotherapy and X-ray therapy. And the patient positioning device can navigate a patient to irradiation position quickly and properly. Furthermore the device is able to monitor movement of the patient׳s position during irradiation.
•A project team headed by University of Tsukuba launched a development of new accelerator based BNCT facility.•The project adopted an 8MeV RFQ+DTL type linac as proton accelerator.•The linac tube is completed and installed in BNCT facility at Tokai village.•Neutron generator device with beryllium target is being also designed and several medical devices as treatment planning system, patient positioning device are being also developed.•We are now developing a new multi-modal Monte-Carlo treatment planning system based on JCDS.
Abstract
J-PARC Main Ring (MR) delivers a slow extracted 30 GeV proton beam to the Hadron Experimental Facility using third-order resonance. One of the critical properties required for the proton ...beam is the flatness of the time structure of the extracted beam (spill structure). We performed a simple beam simulation of the MR slow beam extraction to investigate the effect of the current ripples of the main magnet power supplies on the beam spill structure. In addition, we investigated in the simulation the effects of the feedback control system on the betatron tune using fast Q magnets and the transverse RF system to improve the spill structure. The simulation qualitatively reproduced the measured spill structures. Now the attempts to optimize their parameters for better spill structure are ongoing.
Although radiation skin injuries associated with interventional radiology have been known as a critical issue, there are few reports mentioning direct measurement of the entrance skin dose (ESD). ...Thus, the purpose of this study was to clarify the regional distributions of ESDs in neurointervention.
Using photoluminescence glass dosimeters (PLDs), we measured the ESDs in 32 patients with a median age of 61.5 years. Angiographic parameters, including exposure time, dose-area product (DAP), and the number of digital subtraction angiography (DSA) studies and frames, were recorded. The ESDs of operators were analyzed by the same method.
The maximum ESD of 28 therapeutic procedures was 1.8 +/- 1.3 Gy. Although the averaged ESD on the right temporo-occipital region was higher than that in other regions, disease-specific patterns were not observed. Statistically positive correlations were found between the maximum ESD and exposure time (r = 0.5283, P = .005), DAP (r = 0.7917, P < .001), the number of DSA studies (r = 0.5636, P = .002), and the number of DSA frames (r = 0.8583, P < .001). As for operators, ESDs to the left upper extremity were significantly higher than those to other regions. However, most of the ESDs were <0.2 mGy. Lead protective garments reduced the exposure doses to approximately one half to one tenth.
It was shown that the regional ESD could be measured by applying the PLD. This method should contribute to reducing the dose accumulation in patients as well as in operators.
Because of its fast metabolism gadolinium as a commercial drug was not considered to be suitable for neutron capture therapy. We studied additive effect of gadolinium and boron co-administration ...using colony forming assay. As a result, the survival of tumor cells with additional 5ppm of Gd-DTPA decreased to 1/10 compared to the cells with boron only. Using gadolinium to increase the effect of BNCT instead of additional X-ray irradiation might be beneficial, as such combination complies with the short-time irradiation regimen at the accelerator-based neutron source.
•Gd-DTPA is widely clinically used as a contrast medium for MRI.•Shift to an accelerator-based neutron source is advantageous for gadolinium NCT.•Boron–gadolinium NCT effects on tumor cell lines were significant.•Additional administration of Gd-DTPA might enhance the effect of BPA–BNCT.
A 30 GeV proton beam accelerated in the J-PARC Main Ring (MR) is slowly extracted by the third integer resonant extraction and delivered to the hadron experimental facility. A dynamic bump scheme ...under achromatic condition drastically reduces beam hit rate on the septa devices, and we have attained 51 kW SX operation at 5.2 s cycle with high slow extraction efficiency of 99.5%. A spill duty factor indicating a uniformity of the time structure of the extracted beam is typically 50%. The current SX performance and future plans for improvements will be presented.
Previous studies have compared the oestrogenic properties of phytoestrogens in a wide variety of disparate assays. Since not all phytoestrogens have been tested in each assay, this makes inter-study ...comparisons and ranking oestrogenic potency difficult. In this report, we have compared the oestrogen agonist and antagonist activity of eight phytoestrogens (genistein, daidzein, equol, miroestrol, deoxymiroestrol, 8-prenylnaringenin, coumestrol and resveratrol) in a range of assays all based within the same receptor and cellular context of the MCF7 human breast cancer cell line. The relative binding of each phytoestrogen to oestrogen receptor (ER) of MCF7 cytosol was calculated from the molar excess needed for 50% inhibition of
3Hoestradiol binding (IC
50), and was in the order coumestrol (35×)/8-prenylnaringenin (45×)/deoxymiroestrol (50×)
>
miroestrol (260×)
>
genistein (1000×)
>
equol (4000×)
>
daidzein (not achieved: 40% inhibition at 10
4-fold molar excess)
>
resveratrol (not achieved: 10% inhibition at 10
5-fold molar excess). For cell-based assays, the rank order of potency (estimated in terms of the concentration needed to achieve a response equivalent to 50% of that found with 17β-oestradiol (IC
50)) remained very similar for all the assays whether measuring ligand ability to induce a stably transfected oestrogen-responsive ERE-CAT reporter gene, cell growth in terms of proliferation rate after 7 days or cell growth in terms of saturation density after 14 days. The IC
50 values for these three assays in order were for 17β-oestradiol (1
×
10
−11
M, 1
×
10
−11
M, 2
×
10
−11
M), and in rank order of potency for the phytoestrogens, deoxymiroestrol (1
×
10
−10
M, 3
×
10
−11
M, 2
×
10
−11
M)
>
miroestrol (3
×
10
−10
M, 2
×
10
−10
M, 8
×
10
−11
M)
>
8-prenylnaringenin (1
×
10
−9
M, 3
×
10
−10
M, 3
×
10
−10
M)
>
coumestrol (3
×
10
−8
M, 2
×
10
−8
M, 3
×
10
−8
M)
>
genistein (4
×
10
−8
M, 2
×
10
−8
M, 1
×
10
−8
M)/equol (1
×
10
−7
M, 3
×
10
−8
M, 2
×
10
−8
M)
>
daidzein (3
×
10
−7
M, 2
×
10
−7
M, 4
×
10
−8
M)
>
resveratrol (4
×
10
−6
M, not achieved, not achieved). Despite using the same receptor context of the MCF7 cells, this rank order differed from that determined from receptor binding. The most marked difference was for coumestrol and 8-prenylnaringenin which both displayed a relatively potent ability to displace
3Hoestradiol from cytosolic ER compared with their much lower activity in the cell-based assays. Albeit at varying concentrations, seven of the eight phytoestrogens (all except resveratrol) gave similar maximal responses to that given by 17β-oestradiol in cell-based assays which makes them full oestrogen agonists. We found no evidence for any oestrogen antagonist action of any of these phytoestrogens at concentrations of up to 10
−6
M on either reporter gene induction or on stimulation of cell growth.
Aims
Alterations in microenvironments are a hallmark of cancer, and these alterations in germinomas are of particular significance. Germinoma, the most common subtype of central nervous system germ ...cell tumours, often exhibits massive immune cell infiltration intermingled with tumour cells. The role of these immune cells in germinoma, however, remains unknown.
Methods
We investigated the cellular constituents of immune microenvironments and their clinical impacts on prognosis in 100 germinoma cases.
Results
Patients with germinomas lower in tumour cell content (i.e. higher immune cell infiltration) had a significantly longer progression‐free survival time than those with higher tumour cell contents (P = 0.03). Transcriptome analyses and RNA in‐situ hybridization indicated that infiltrating immune cells comprised a wide variety of cell types, including lymphocytes and myelocyte‐lineage cells. High expression of CD4 was significantly associated with good prognosis, whereas elevated nitric oxide synthase 2 was associated with poor prognosis. PD1 (PDCD1) was expressed by immune cells present in most germinomas (93.8%), and PD‐L1 (CD274) expression was found in tumour cells in the majority of germinomas examined (73.5%).
Conclusions
The collective data strongly suggest that infiltrating immune cells play an important role in predicting treatment response. Further investigation should lead to additional categorization of germinoma to safely reduce treatment intensity depending on tumour/immune cell balance and to develop possible future immunotherapies.
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