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CheckMate 141, an open-label, randomized phase III trial of nivolumab, indicated that treatment with nivolumab prolonged overall survival of patients with platinum-refractory, recurrent head and neck squamous cell carcinoma. Herein, we describe a case of brain metastasis of parotid carcinoma in which a good response was achieved after nivolumab treatment. The patient was a 67-year-old woman with parotid carcinoma (cT4bN0M0) who received induction chemotherapy followed by chemoradiation. Computed tomography and magnetic resonance imaging performed 10 weeks after the primary treatment revealed a residual tumor and brain and lung metastases. Thereafter, chemotherapy comprising cisplatin, 5-FU, and cetuximab was performed. Unfortunately, the tumor volume increased 5 months after chemotherapy, after which she received immunotherapy with biweekly nivolumab. After six cycles of nivolumab administration, the brain and lung metastases shrank markedly. Nivolumab had an intracranial effect in the patient with brain metastases of parotid carcinoma. This case report highlights the efficacy of nivolumab in the management of head and neck cancer with brain metastasis.

To increase the beam intensity of cyclotrons used for producing radionuclides, beam loss during extraction must be reduced. Extraction efficiency is limited by the beam parameters in front of the deflector, especially angular distribution. Computer simulation of the second harmonic mode for 18 MeV protons, which is frequently used, has been carried out to understand beam behavior in a cyclotron. The extraction efficiency is determined by the width of the angular distribution of particles in the phase space plot at the deflector. An effective method to reduce the width is to shorten the bunch at injection. The simulation shows that the bunch phase length at injection must be ⩽30° to realize a 30 μA extraction beam current and satisfy the deflector heat limit of 200 W.

A singly charged ion source (SCIS) has been designed using a newly developed three-dimensional particle-in-cell (PIC) code. The SCIS is to be used in an isotope separation on-line (ISOL) system that provides 11C ions for heavy-ion cancer therapy with simultaneous verification of the dose distribution using positron emission tomography. The SCIS uses low-energy electron beams to produce singly charged carbon ions efficiently and maintain a high vacuum in the ISOL system. Because the SCIS has to realize a production efficiency of 1% if its carbon ions are to be used in the ISOL system, a suitable design for the SCIS was investigated by using the developed PIC code to study the beam trajectories of the electrons and extracted ions. The simulation results show that hollow electron beams are produced in the designed SCIS resulting in a high effective electron current. The results also predict that the designed SCIS would realize ion-production efficiencies (IPEs) of eSCIS ≃ 6.7% for CO2+ production from CO2 gas and eSCIS ≃ 0.1% for C+ production from CH4 gas. Moreover, to examine the validity of the developed code and confirm that the SCIS was able to be designed appropriately, the space-charge-limited current of the electron gun and the total IPE obtained by adding the IPEs of each ion were compared between the experiment and the simulation.

Hemorrhage following tonsillectomy is still a major complication despite the progress in medical technology. Celecoxib is a selective COX-2 inhibitor and has a lower effect of platelet aggregation compared with conventional non-steroidal anti-inflammatory drugs (NSAIDs). We investigated whether or not the selection of celecoxib would reduce the risk of hemorrhage and provide a good analgesic effect following tonsillectomy in comparison with the use of loxoprofen (a conventional NSAID). We divided 107 cases of tonsillectomy into two groups by the kind of analgesic prescribed; the celecoxib group (n=55) and the loxoprofen group (n=52). Regarding the effective rate of the analgesic effect, the loxoprofen group scored 93.3% and the celecoxib group scored 68.6%. There was a significant difference between them (p=0.0003). Regarding side effects, the celecoxib group showed no side effects, whereas 8.0% of the loxoprofen group developed abdominal pain. There were no statistically significant differences between the changes in the VAS scale regarding the pain (p=0.834), the prescription periods of analgesic (p=0.485), the amount of food intake during the hospitalization (p=0.579), the rescue dosage rate (p=0.585), periods of usage (p=0.198) and the last dosage day. As for the tendency and the grade of postoperative hemorrhage, there were no statistically differences between the two groups (p=0.220). The rates of occurrence of late-onset hemorrhage (i.e. after the postoperative eleventh day) were 0.0% (0/11) in the the celecoxib group (n=11) and 31.2% (5/16) in the the loxoprofen group showing a statistically differences between them (p=0.049). Our results suggest that Celecoxib might reduce the risk of late-onset hemorrhage after the postoperative eleventh day with few side effects, so it could be a useful analgesic drug following tonsillectomy. However, it might be necessary to consider administration in combination with acetaminophen because Celecoxib has insufficient analgesic effect following tonsillectomy.

In this study, we retrospectively evaluated the clinical features of the pediatric acquired cholesteatoma based on the staging criteria for cholesteatoma 2010 Japan. Between 2001 and 2012, total of 36 pediatric patients underwent otologic surgery at our hospital, 29 patients (29 ears) with pars flaccida cholesteatoma and 7 patients (7 ears) with pars tensa cholesteatoma. The age range was 4 to 15 years, (median was 10.5 years). Stage 11 was the most common for both the pars flaccida and pars tensa. A staged operation was performed in 24 ears with pars flaccida cholesteatoma, and 4 ears with pars tensa cholesteatoma. The success rate of hearing improvement was 72% (21/29) in pars flaccida cholesteatoma and 57% (4/7) in pars tensa cholesteatoma. Hearing improvement decreased in advanced cases. In staged operations, residual cholesteatoma was found in 11 ears (46%) with pars flaccida cholesteatoma and 2 ears (50%) with pars tensa cholesteatoma. These results suggest that the residual rate of cholesteatoma in the pediatric population is high. In conclusion, a high rate of residual cholesteatoma in the pediatric population was observed in our study. Thus a staged operation would be the recommended treatment approach in pediatric acquired cholesteatoma.

The cricoid cartilage has been regarded as an extremely important organ because it plays important role in both of phonation and breathing. We herein report on two different types of surgical procedure for laryngotracheal diseases with aggressive resection of the cricoid cartilage. The first procedure is a tracheostomaplasty by partial resection of the cricoid cartilage. A tracheostoma is made by resection of the cricoid cartilage in the range of approximately a one-third front. This method is effective for such cases having difficulty in tracheostomy owing their backgrounds with such condition as neck stiffness, obesity, higher displacement of the brachiocephalic artery, short neck, thyroid disease and so on. We applied this procedure for eight cases with such difficult backgrounds. In all cases, we were able to make a good tracheostoma and the postoperative courses were uneventful. The second procedure is a glottic closure with resection of the cricoid cartilage and thyroid cartilage. We applied this procedure for six cases with intractable dysphagia. One case had a postoperative bleeding. We were able to make good conditions in all cases with a large tracheostoma and no pharyngeal-tracheal leakage. In conclusion, the surgical procedure involving resection of the cricoid cartilage can be applied to some laryngotracheal diseases.

The Great East Japan Earthquake has occurred on March 11, 2011, in the Tohoku District of Japan. Due to the earthquake, big tsunamis were induced, and they rushed to the Fukushima Nuclear Power Stations, causing severe accidents. Radioactive materials including I-131, Cs-137 and so on were emitted from the plant to the environment. The Japanese government, Fukushima prefectural government and other local governments have struggled against the accidents. The restricted area and deliberate evacuation area are set by the government, and the residents are evacuated. The dose rates in and around Fukushima Prefecture have been monitored by the governments and other involved organizations. Fukushima government has started the health management survey for all residents in Fukushima Prefecture including the questions on their activities for the estimations of their external doses.

We experienced a patient who required a high-dose opioid for pain control, a 39-year-old male who was diagnosed as having primary small cell carcinoma of the larynx. He received concurrent chemoradiotherapy with cisplatin plus etoposide, and achieved a complete response. Four months later, multiple bone and distant metastases became evident. He was treated with concurrent platinum-based chemotherapy and an opioid, NSAIDs, adjuvant analgesics, radioactive strontium and palliative radiotherapy for management of the pain associated with the bone metastases. The pain gradually became stronger, and we increased the opioid dose up to 16680 mg/day in terms of oral morphine. Finally the pain was successfully managed until his death.

Objective Increased understanding of cytokines and their associated proteoglycans will contribute to the investigation of the formation of nasal polyps. Recently, some studies have suggested that syndecan-1 ectodomains are shed in response to low respiratory infection, but no studies regarding nasal and paranasal diseases have been reported. Transforming growth factor-beta (TGF-β) is involved in the regulation of nasal polyps, especially in processes crucial to the initiation, maintenance, and resolution of inflammatory responses. In the nasal mucosa and nasal polyps, we analyzed the expression of syndecan-1, which readily promotes infection, and TGF-β, which plays a role in syndecan-1 activity. Methods Fifteen patients who underwent turbinectomy for the treatment of nasal obstruction and seventeen patients with nasal polyps who underwent nasal endoscopic sinus surgery were included in this study. The localization of syndecan-1 and TGF-β in the nasal mucosa and nasal polyps was investigated by immunohistochemistry, and mRNA transcript levels of syndecan-1 and TGF-β were examined using quantitative real-time PCR. Results Immunohistochemical staining revealed that the expression of syndecan-1 in the nasal mucosa and nasal polyps was co-localized with TGF-β. The mean mRNA expression values for syndecan-1 and TGF-β were higher in nasal polyps compared to the nasal mucosa. Conclusions This is the first report showing expression of syndecan-1 in the nasal mucosa and nasal polyps. In nasal polyps, syndecan-1 expression may be increased by an unknown mechanism, permitting infection and inducing larger nasal polyps. We hypothesize that the accumulation of TGF-β, which is involved in the pathophysiological development of nasal polyps, may result in a change in the binding properties of syndecan-1 at inflammatory sites.

This study describes measurements on secondary particles produced by a 290 MeV/n Spread Out Bragg Peak (SOBP) carbon beam. Microdosimetric distributions of secondary fragments from the SOBP carbon beam have been measured by using a new tissue equivalent proportional counter (TEPC) system at the Heavy Ion Medical Accelerator in Chiba of the National Institute of Radiological Sciences. The new TEPC system consists of a TEPC, two solid-state detectors (SSD) and a scintillation counter (FSC: forward scintillation counter). The SSDs and FSC can separately identify charged fragments and secondary neutrons produced by the incident carbon ions. Microdosimetric distributions were measured for secondary particles including neutrons produced by a body-simulated phantom consisting of various PMMA plates (thickness: 0, 34.81, 55.2, 60.95, 64.83, 95.03, 114.79, 124.69, 135.2 and 144.98 mm, respectively) to cover the SOBP (at 60-125 mm depth). The new system can separately determine produced fragments from the incident SOBP carbon beam in a body-simulated phantom.

The effects of irradiation of a Nd–Fe–B permanent magnet by fast neutrons was investigated. The decrease in measured magnetic flux density at the center of the magnets were 0.6%, 6.9%, 25.2% and 47.3% after continuous irradiation of 1.1 kGy, 3.7 kGy, 5.6 kGy and 7.4 kGy, respectively. On the other hand, the decrease due to non-continuous irradiation, in which the magnet was first irradiated at 3.7 kGy, then irradiated again at 3.7 kGy nine months later, was 14% smaller than that of continuous irradiation, even for the same total dose. The temperature coefficient of the magnetization did not change with irradiation. Some radioactive materials, such as 147Nd, 151Pm, and 54Mn, were detected in the magnet after irradiation.

The quality of high-temperature superconductors (HTSs) is rapidly increasing, and they can be used in power systems such as SMES systems and in industries as Si single-crystal growth pullers. In the future, HTS conductors are expected to be used for the magnets in nuclear fusion reactors or accelerators. In such applications, HTS conductors will be exposed to radiation. As a result, HTS conductors become radioactive making the operation and maintenance of the reactors or accelerators difficult; this also leads to an increase in the amount of nuclear waste generated. Therefore, we carry out experiments on the radiation damage in HTS conductors to study the characteristics of HTS conductors in radiation environments and to create an industrial database of the radiation effects on HTSs. We also carry out radioactive analyses on HTS conductors in order to clarify the relationship between the irradiation dose and the activity of HTS conductors. In this study, we prepared YBCO and Bi-2223 tapes and carried out the following preliminary experiments: (a) irradiation of the sample HTS tapes with 2-MeV neutrons at room temperature without transport current and (b) study of neutron-induced radioactivity by gamma-ray spectrometry using a Ge detector after the irradiation.

A compact injector for a heavy-ion medical-accelerator complex was developed. It consists of an electron-cyclotron-resonance ion-source (ECRIS) and two linacs, which are a radio-frequency-quadrupole (RFQ) linac and an Interdigital H-mode drift-tube-linac (IH-DTL). Beam acceleration tests of the compact injector were performed, and the designed beam quality was verified by the measured results, as reported earlier. Because the method of alternating-phase-focusing (APF) was used for beam focusing of the IH-DTL, the motion of beam ions would be sensitive to gap-voltage errors, caused during tuning of the gap-voltage distribution and by automatic-frequency tuning in actual operation. To study the effects of voltage errors to beam quality, further measurements were performed during acceleration tests. In this report, the effects of voltage errors for the APF IH-DTL are discussed.

Absorbed doses from main charged-particle beams and charged-particle fragments have been measured with high accuracy for particle therapy, but there are few reports for doses from neutron components produced as fragments. This study describes the measurements on neutron doses produced by carbon beams; microdosimetric distributions of secondary neutrons produced by 290 MeV/nucleon carbon beams have been measured by using a tissue equivalent proportional counter at the Heavy Ion Medical Accelerator in Chiba, Japan at the National Institute of Radiological Sciences. The microdosimetric distributions of the secondary neutron were measured on the distal and lateral faces of a body-simulated acrylic phantom (300 mm height x 300 mm width x 253 mm thickness). To confirm the dose measurements, the neutron energy spectra produced by incident carbon beams in the acrylic phantom were simulated by the particle and heavy ion transport code system. The absorbed doses obtained by multiplying the simulated neutron energy spectra with the kerma factor calculated by MCNPX agree with the corresponding experimental data fairly well. Downstream of the Bragg peak, the ratio of the neutron dose to the carbon dose at the Bragg peak was found to be a maximum of 1.4 x 10(-4) and the ratio of neutron dose was a maximum of 3.0 x 10(-7) at a lateral face of the acrylic phantom. The ratios of neutrons to charged particle fragments were 11% to 89% in the absorbed doses at the lateral and the distal faces of the acrylic phantom. We can conclude that the treatment dose will not induce serious secondary neutron effects at distances greater than 90 mm from the Bragg peak in carbon particle therapy.

A compact injector, designed for a heavy-ion medical accelerator complex, was constructed. It consists of an Electron-Cyclotron-Resonance Ion-Source (ECRIS) and two linacs, which are a Radio-Frequency-Quadrupole linac and an Interdigital H-mode Drift-Tube-Linac (IH-DTL) having the same operating frequency of 200 MHz. For beam focusing of the IH-DTL, the method of Alternating-Phase-Focusing (APF) was employed. The compact injector can accelerate heavy ions having a charge-to-mass ratio of q m = 1 3 up to 4.0 MeV / u . Use of the APF IH-DTL and operating frequency of 200 MHz allowed us to design compact linacs; the total length of the two linacs is less than 6 m. Beam-acceleration tests of the compact injector system were performed. The measured intensity of accelerated C 4 + 12 beams with the compact injector was 380 e μ A . Beam transmission of the APF IH-DTL was estimated to be as high as 96%, which is comparable to the value calculated by a simulation code. Transverse phase-space and energy distributions of accelerated beams were measured and compared with those calculated by the simulation code, and we found that they were agreed well with each other.

Clinical trials of carbon radiotherapy started at HIMAC in 1994 using three treatment rooms and four beam ports, two horizontal and two vertical. The broad beam method was adopted to make a three-dimensionally uniform field at an isocenter. A spot beam extracted from an accelerator was laterally spread out by using a pair of wobbler magnets and a scatterer. A bar ridge filter modulated the beam energy to obtain the spread out Bragg peak (SOBP). The SOBP was designed to be flat in terms of the biological dose based on the consideration that the field consisted of various beams with different LET. Finally, the field of 20 cm in diameter with +/- 2.5% uniformity was formed at the isocenter. The width of the maximum SOBP was 15 cm. When treating the lung or liver, organs that move due to breathing, the beam was irradiated only during the expiration period in a respiration-gated irradiation method. This reduced the treatment margin of the moving target. In order to prevent normal tissues adjacent to the target volume from irradiation by an unwanted dose, a layer-stacking method was developed. In this method, thin SOBP layers which have different ranges were piled up step by step from the distal end to the entrance of the target volume. At the same time, a multi-leaf collimator was used to change the aperture shape to match the shape of each layer to the cross-sectional shape of the target. This method has been applied to rather large volume cancers including bone and soft-tissue cancers. Only a few serious problems in the irradiation systems have been encountered since the beginning of the clinical trials. Overall the systems have been working stably and reliably.

Microdosimetric single event spectra as a function of depth in a phantom for the 290 MeV/nucleon therapeutic carbon beam at HIMAC were measured by using a tissue equivalent proportional counter (TEPC). Two types of geometries were used: one is a fragment particle identification measurement (PID-mode) with time of flight (TOF) method without a backward phantom, and the other is an in-phantom measurement (IPM-mode) with a backward phantom. On the PID-mode geometry, fragments produced by carbon beam in a phantom are identified by the DeltaE-TOF distribution between two scintillation counters positioned up- and down-stream relative to the tissue equivalent proportional counter (TEPC). Lineal energy distributions for carbon and five ion fragments (proton, helium, lithium, beryllium and boron) were obtained in the lineal-energy range of 0.1-1000 keV/microm at eight depths (7.9-147.9 mm) in an acrylic phantom. In the IPM-mode geometry, the total lineal energy distributions measured at eight depths (61.9-322.9 mm) were compared with the distributions in the PID-mode. Both spectra are consistent with each other. This shows that the PID-mode measurement can be discussed as the equivalent of the phantom measurement. The dose distribution of the carbon beam and fragments were obtained separately. In the depth dose curve, the Bragg peak was observed. Relative biological effectiveness (RBE) for the carbon beam in the acrylic phantom was obtained based on a biological response function as a lineal-energy. The RBE of carbon beam had a maximum of 4.5 at the Bragg peak. Downstream of the Bragg peak, the RBE rapidly decreases. The RBE of fragments is dominated by Boron particles around the Bragg peak region.

1995年から2003年の間に，当科で一次治療を施行した喉頭扁平上皮癌98例を対象に，臨床統計および治療内容別の治療成績について検討した。性別は男性87例，女性11例であり，男女比は8:1であった。年齢は38歳から92歳までで，平均年齢は全体で66.7歳であった。病期分類は，stageI 49例(50.0%)，stageII 22例(22.4%)，stageIII 9例(9.2%)，およびstageIV 18例(18.4%)であった。発生部位別分類は，声門癌62例(63.3%)，声門上癌35例(35.7%)，および声門下癌1例(1.0%)であった。病期別の3年生存率，5年生存率ではstage Iが100%，95.1%，stage IIが100%，100%，stage IIIが77.8%，72.9%，stage IVが68.8%，60.6％であり，全体では，93.1%，88.1%であった。T分類別の5年累積喉頭温存率では，T1が93.4%，T2が92.3%，T3が54.5%，T4が33.9%であり，全体では83.4%であった。stageIII，IV例において，CDDP，5-FUによる化学放射線同時併用療法を施行した11例中10例がCRであり，喉頭温存可能であった(CR期間は36～107カ月，平均60.9カ月)。進行喉頭癌において，化学放射線同時併用療法はもっとも有効な治療法の一つと考える。

A compact Drift-Tube-Linac (DTL) using an Interdigital H-mode (IH) cavity was designed for an injector of medical accelerators. For beam focusing, the method of Alternating-Phase-Focusing (APF) was applied. The APF IH-DTL can accelerate heavy ions having a charge-to-mass ratio of q / m = 1 3 up to 4.0 MeV / u . Having optimized an array of synchronous phases for cells, namely arranging drift tubes and gaps appropriately, both longitudinal and transverse focusing strengths were produced just with the rf acceleration field, and therefore no focusing element or cooling equipments had to be installed in the cavity. This allowed us to employ a rather high operating frequency, and hence to design a compact and cost-effective cavity. A further advantage of the APF linac can be found in its operation. Since the parameters to be adjusted are just the level and phase of the input rf, beam tuning can be made with ease. Consequently, the APF linac is suitable for an injector for medical accelerators. Tuning methods of the gap voltages and cavity frequency as well as the design of the cavity for APF IH-DTL have been developed. After constructing the cavity, measurements of the electric field and tuning of the gap voltages were performed. Finally, the rf power was fed into the cavity. In this paper, the design and results of the measurements are described.

A compact injector for medical accelerators was designed. The injector consists of a compact Electron-Cyclotron-Resonance Ion Source (ECRIS) and two linacs, which are a Radio-Frequency-Quadrupole (RFQ) linac and an Interdigital H-mode Drift-Tube-Linac (IH-DTL) having the same operating frequency of 200 MHz. For beam focusing of the IH-DTL, the method of Alternating-Phase-Focusing (APF) was applied. Before constructing the compact injector, a model cavity of the IH-DTL was manufactured, and measurements of the electric-field distributions were performed. The gap-voltage distributions, obtained by integrating the measured electric field, were compared with those calculated using a three-dimensional field solver. The accuracy of the calculated field distributions is discussed. Finally, fine adjustments of the gap voltages using inductive tuners are described.

2000年9月から2004年8月までに，舌がん8症例に対して高線量率組織内照射を施行した。表在型2例，浸潤型6例で，T1：1例，T2：5例，T3：1例，T4a：1例であった。組織内照射は，1回5から6Gy，1日2回，総線量50から60Gyを施行した。また浸潤型に対しては外部照射を20から30Gy併用した。新鮮例に限れば，2年局所制御率は83%であった。認知症を合併していた1例をのぞき予定どおりの治療が施行できた。高線量率組織内照射は有用であり高齢者においても安全に施行できた。

1999年4月から2004年6月までに, 26人 (27病変) の頭頸部がんにゴールドグレインによる治療をおこなった。23病変は舌がんであり, その他は口腔底がん2, 右頬粘膜がん1, 中咽頭がん1例であった。表在型は13例, 外方発育型は14例であった。外方発育型の9例に, 腫瘍の厚みを減らす目的で外部照射を併用した。外部照射は, 1回線量2Gy, 総線量20Gyまたは30Gyを投与した。もちいたゴールドグレインは10個から13個 (中央値10個) で, ゴールドグレイン単独治療群では, 74Gyから85Gy (中央値80Gy), 外部照射併用群では, 71Gyから83Gy (中央値76Gy) を投与した。27病変の内1病変は治療後4ヵ月目に再発, 1病変は腫瘍が残存した。2年局所制御率は92%であった。ゴールドグレインは, 非侵襲的な治療法であり, 高齢または合併症をもつがん患者にも安全に施行できた。

A three-dimensional irradiation system using a broad beam has been installed for heavy-ion cancer therapy at the Heavy Ion Medical Accelerator in Chiba (HIMAC) facility. Only the target region is irradiated at the 100% dose level; the dose level at other parts of irradiated tissues is less, using a range shifter, a multileaf collimator and a compensator. The devices are the same as those used in two-dimensional irradiation, except that the setting values of the devices can be dynamically changed during the treatment. The thickness of the absorber and the aperture of the multileaf collimator are dynamically controlled during irradiation, so that the Bragg peak is swept in the depth direction and the Bragg peak outside of the target volume is blocked by the multileaf collimator. The performance of this system was checked by irradiation of a phantom using a 290 MeV/nucleon carbon beam. The dose distribution realized by this three-dimensional irradiation agreed satisfactorily with the planned one.

For atomic force microscope (AFM) observations of minute tracks ( ⩽1 μ m) in the CR-39 track detector, an accurate method to measure an extremely small amount of bulk etch is required. A simple method for direct measurements of the bulk etch using AFM was developed. Before the etching, a part of the CR-39 surface was covered with epoxy adhesive resin. The amount of bulk etch was measured as a level difference between the etched surface and the unetched original surface which has been covered with epoxy resin during its chemical etching processing. The details of this method are reported and its limitations are discussed in comparison to a conventional measuring method using tracks of fission fragments.

The great east Japan earthquake and subsequent tsunamis caused Fukushima Dai-ichi Nuclear Power Plant (NPP) accident. National Institute of Radiological Sciences (NIRS) developed the external dose estimation system for Fukushima residents. The system is being used in the Fukushima health management survey. The doses can be obtained by superimposing the behavior data of the residents on the dose rate maps. For grasping the doses, 18 evacuation patterns of the residents were assumed by considering the actual evacuation information before using the survey data. The doses of the residents from the deliberate evacuation area were relatively higher than those from the area within 20 km radius. The estimated doses varied from around 1 to 6 mSv for the residents evacuated from the representative places in the deliberate evacuation area. The maximum dose in 18 evacuation patterns was estimated to be 19 mSv.

The NIRS heavy-ion two-synchrotron medical facility, HIMAC, was approved in the 1987 fiscal year and clinical trials were started in late June 1994 as previously arranged. The operation experiences show that the entire HIMAC facility can work well with high stability and excellent reproducibility. For example, the intensity of beam extracted slowly from the rings can be reduced as low as 500 particles per pulse because stable and reproducible acceleration can be achieved in the rings in spite of no beam feedback. This performance enables direct counting of the beam and its fragments in the preparatory experiments toward clinical treatments and provides a promising basis for acceleration and storage of radioactive beams toward simultaneous treatment and diagnosis in future.

Objective: Trefoil factor family peptides (TFFs) are the secretory products of mucous cells and are closely associated with mucins. TFFs appear to be important in mucosal healing processes. Although TFF1/3 are expressed in the human respiratory tract, their role in the nasal mucosa is not thoroughly understood. We investigated the association between TFFs and mucins and the role TFFs in the human nasal mucosa. Material and methods: Patients undergoing turbinectomy were included and it was determined whether patients had nasal allergies or not. The localization of TFF1/3, MUC5AC/5B expression was investigated using immunohistochemistry. The levels of the mRNA transcripts were examined using quantitative real-time PCR. Results: TFF1/3 had a similar pattern of localization in epithelial goblet cells and submucosal glandular cells. TFF1/3 co-localized with MUC5AC in the epithelium, and co-localized with MUC5B in the epithelium and the submucosal glandular cells. The levels of TFF1/3 and MUC5B mRNA in allergic patients were significantly increased. Conclusion: Our results suggest that TFF1/3 may associate with MUC5AC and MUC5B in the nasal mucosa, and that up-regulation of TFF1/3 and MUC5B may play an important role in the clinical condition of the nasal allergic mucosa.

Fracture Toughness of HIP-sintered silicon nitride decreased with increasing temperature up to 1200°C. The brittle-to-ductile transition was observed in the temperature range from 1200°C to 1275°C: the fracture toughness rapidly increased in the transition region. Above the transition temperature, the fracture toughness decreased with increasing temperature. Fracture toughness of sialon increased with increasing temperature. Transition of fracture mechanism was observed in sialon around 1300°C. The differences of temperature dependence of fracture toughness between two materials are interpreted in terms of the effects of grain-boundary glass phase on fracture.

Strength and fracture toughness tests were carried out on HIP-sintered SiAlON at elevated temperatures. Above 1200°C the strength decreased with increasing temperature. In the temperature range from 1400°C to 1600°C, the strength increased with temperature. On the other hand, the fracture toughness monotonously increased with temperature up to 1400°C. Above 1400°C the fracture toughness gradually decreased with increasing temperature. A stable crack growth region was observed both on the strength specimens and fracture toughness specimens, tested beyond 1200°C. From the detailed observation of the stable crack growth region, β-SiAlON particles were found to be oriented along the tensile direction. Increment of strength and fracture toughness beyond 1400°C may be due to the stable crack growth. The difference in temperature dependence between the strength and fracture toughness may be caused by high- temperature slow crack growth.

Purpose To compare the effects of carbon beam irradiation with those of proton beam irradiation on the physiology of the retina of rats. Methods and Materials Eight-week-old Wister rats were used. The right eyes were irradiated with carbon beam (1, 2, 4, 8, and 16 Gy) or proton beam (4, 8, 16, and 24 Gy) with the rats under general anesthesia. Electroretinograms were recorded 1, 3, 6, and 12 months after the irradiation, and the amplitudes of the a and b waves were compared with those of control rats. Results The amplitude of b waves was reduced more than that of a waves at lower irradiation doses with both types of irradiation. With carbon ion irradiation, the amplitudes of the b wave were significantly reduced after radiation doses of 8 and 16 Gy at 6 months and by radiation doses of 4, 8, and 16 Gy at 12 months. With proton beam irradiation, the b -wave amplitudes were significantly reduced after 16 and 24 Gy at 6 months and with doses of 8 Gy or greater at 12 months. For the maximum b -wave amplitude, a significant difference was observed in rats irradiated with carbon beams of 4 Gy or more and with proton beams of 8 Gy or more at 12 months after irradiation. Conclusions These results indicate that carbon beam irradiation is about two times more damaging than proton beam irradiation on the rat retina at the same dose.

Fracture toughness tests were carried out on HIP-sintered silicon nitride at elevated temperatures. The fracture toughness gradually decreased with an increase in temperature up to 1200°C. In the temperature range from 1200°C to 1275°C, a steel-like brittle-to-ductile transition of fracture toughness was observed: the fracture toughness rapidly increased from 4MPa√m to 8MPa√m. Above these temperatures, stable crack growth was observed. From the detailed observation of the stable crack growth region, β-Si3N4 particles were found to be oriented in the tensile direction. The stable crack growth occurred accompanying with bridging and pulling out of β-Si3N4 particles. The transition behavior of fracture toughness results from the transition of fracture mechanism from the stresscontrolled intergranular fracture to the pulling-out of β-Si3N4 particles with shear deformation of intergranular glass phase. The transition temperature was thought to be consistent with the softening point of the intergranular glass phase. The same transition behavior of fracture mechanism was found in the bending strength test.

The fracture toughnesses of Si3N4 (two lots), SiC, TiB2, ZrO2 and Al2O3 were obtained by bending precracked specimens in three different ways: by the bridge compression (BC) method, by fatigue precracking from a crack introduced by the BC method (FP method), and by the controlled surface flaw (CSF) method. For comparison, fracture toughness evaluations by the chevron notch (CN) method and the indentation fracture (IF) method were also carried out. Furthermore, the effect of loading rate on fracture toughness of FP specimens was examined together with a crack propagation test under static fatigue. The KIC values evaluated by FP, CSF and CN methods showed a reasonable agreement with each other for all six of the ceramics tested, while the evaluation by BC and IF methods tended to give considerably lower values than those obtained by the three methods. The normalization of these KIC and KISCC values was done by a theoretical KIC value, which was derived according to the Griffith criterion for unstable fracture. The different fracture modes of these materials were successfully characterized in correlation to the normalized fracture toughness.

The radiation-transport code PHITS with an event generator mode has been applied to analyze energy depositions of electrons and charged heavy particles in two spherical phantoms and a voxel-based mouse phantom upon neutron irradiation. The calculations using the spherical phantoms quantitatively clarified the type and energy of charged particles which are released through interactions of neutrons with the phantom elements and contribute to the radiation dose. The relative contribution of electrons increased with an increase in the size of the phantom and with a decrease in the energy of the incident neutrons. Calculations with the voxel-based mouse phantom for 2.0-MeV neutron irradiation revealed that the doses to different locations inside the body are uniform, and that the energy is mainly deposited by recoil protons. The present study has demonstrated that analysis using PHITS can yield dose distributions that are accurate enough for RBE evaluation.

An international intercomparison of integrating detectors was conducted at NIRS (National Institute of Radiological Science, Japan) with a 24.4 m3 inner volume walk-in radon chamber that has systems to control radon concentration, temperature and humidity. During the first intercomparison (05.2007) four groups participated from four countries and for the second intercomparison (10.2007) 17 participants were involved from 11 countries. Most of detectors are in good agreement with each other when compared to the radon level provided by the radon chamber. It appeared that the 70% of detectors are unified within the 20% margin of uncertainty.

Passive detectors used for large‐scale and long‐term surveys are generally calibrated in a well‐controlled environment such as a radon chamber. It has been also pointed out that some of them are sensitive to thoron. Thus it is necessary to check the thoron contribution to the detector response with the proposed or similar test before practical use. The NIRS accommodates radon/aerosol and thoron chambers for quality assurance and quality control of radon measurements. Thus both chambers work so well that they can supply us with the calibration technique and consequently, a good level of knowledge of the radon and thoron issue.

For quality assurance, gas‐filled ionization chamber method was tested at two reference facilities for radon calibration: EML (USA) and PTB (Germany). Consequently, the radon concentrations estimated by the ionization chamber method were in good agreement with the reference radon concentrations provided by EML as well as PTB.