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For proton spot scanning, use of a real-time-image gating technique incorporating an implanted marker and dual fluoroscopy facilitates mitigation of the dose distribution deterioration caused by interplay effects. This study explored the advantages of using a real-time-image gating technique, with a focus on prostate cancer. Two patient-positioning methods using fiducial markers were compared: (i) patient positioning only before beam delivery, and (ii) patient positioning both before and during beam delivery using a real-time-gating technique. For each scenario, dose distributions were simulated using the CT images of nine prostate cancer patients. Treatment plans were generated using a single-field proton beam with 3-mm and 6-mm lateral margins. During beam delivery, the prostate was assumed to move by 5 mm in four directions that were perpendicular to the beam direction at one of three separate timings (i.e. after the completion of the first, second and third quartiles of the total delivery of spot irradiation). Using a 3-mm margin and second quartile motion timing, the averaged values for ΔD99, ΔD95, ΔD5 and D5–95 were 5.1%, 3.3%, 3.6% and 9.0%, respectively, for Scenario (i) and 2.1%, 1.5%, 0.5% and 4.1%, respectively, for Scenario (ii). The margin expansion from 3 mm to 6 mm reduced the size of ΔD99, ΔD95, ΔD5 and D5–95 only with Scenario (i). These results indicate that patient positioning during beam delivery is an effective way to obtain better target coverage and uniformity while reducing the target margin when the prostate moves during irradiation.

Purpose This treatment planning study was conducted to determine whether spot scanning proton beam therapy (SSPT) reduces the risk of grade ⩾3 hematologic toxicity (HT3+) compared with intensity modulated radiation therapy (IMRT) for postoperative whole pelvic radiation therapy (WPRT). Methods and materials The normal tissue complication probability (NTCP) of the risk of HT3+ was used as an in silico surrogate marker in this analysis. IMRT and SSPT plans were created for 13 gynecologic malignancy patients who had received hysterectomies. The IMRT plans were generated using the 7-fields step and shoot technique. The SSPT plans were generated using anterior-posterior field with single field optimization. Using the relative biological effectives (RBE) value of 1.0 for IMRT and 1.1 for SSPT, the prescribed dose was 45 Gy(RBE) in 1.8 Gy(RBE) per fractions for 95% of the planning target volume (PTV). The homogeneity index (HI) and the conformity index (CI) of the PTV were also compared. Results The bone marrow (BM) and femoral head doses using SSPT were significantly lower than with IMRT. The NTCP modeling analysis showed that the risk of HT3+ using SSPT was significantly lower than with IMRT (NTCP = 0.04 ± 0.01 and 0.19 ± 0.03, p = 0.0002, respectively). There were no significant differences in the CI and HI of the PTV between IMRT and SSPT (CI = 0.97 ± 0.01 and 0.96 ± 0.02, p = 0.3177, and HI = 1.24 ± 0.11 and 1.27 ± 0.05, p = 0.8473, respectively). Conclusion The SSPT achieves significant reductions in the dose to BM without compromising target coverage, compared with IMRT. The NTCP value for HT3+ in SSPT was significantly lower than in IMRT.

Given the same tension load capacity, the anchorage length of post-installed bonded anchor bolts is extremely short compared with the anchorage length of cast-in-place anchor bolts. Under the Architectural Institute of Japan's “Design Recommendations for Composite Construction, Part 4: Design Recommendations for Anchor Bolts” revised in 2010, the design of the anchorage zone of anchor bolts is based on the concept that the anchorage zone is the same regardless of whether anchors are cast in place or post installed. With regard to the design method for the tension load capacity of bonded anchors, this study investigates whether evaluation based on the maximum load determined from the bond strength between the adhesive and concrete is appropriate, and proposes a tension load capacity evaluation formula. Further, it verifies that the estimates of bond strength, which declines as the result of the edge distance effect and group effect, among other things, are equivalent with the bond strengths used for cast-in-place deformed bars.接着系あと施工アンカーボルトの引張支持力に対する定着長は，先付けアンカーボルトの定着長さに比べて非常に短い。2010年に改定された「日本建築学会：各種合成構造設計指針，第4編 各種アンカーボルト設計指針」では，アンカーボルトの定着部設計は，先付け・後打ちといった工法の種別によらず同一であるという思想に基づいている。接着系アンカーの引張支持力に対する設計法は，接着剤とコンクリートとの付着力により決まる耐力で評価する手法が適切であることを検証し，引張支持力評価式を示している。また，へりあき・群効果等で低減した付着強度は先付けの異形鉄筋で用いられている付着強度と同様な算定値となることを検証している。

To investigate the effectiveness of real-time-image gated proton beam therapy for lung tumors and to establish a suitable size for the gating window (GW).A proton beam gated by a fiducial marker entering a preassigned GW (as monitored by 2 fluoroscopy units) was used with 7 lung cancer patients. Seven treatment plans were generated: real-time-image gated proton beam therapy with GW sizes of ±1, 2, 3, 4, 5, and 8 mm and free-breathing proton therapy. The prescribed dose was 70 Gy (relative biological effectiveness)/10 fractions to 99% of the target. Each of the 3-dimensional marker positions in the time series was associated with the appropriate 4-dimensional computed tomography phase. The 4-dimensional dose calculations were performed. The dose distribution in each respiratory phase was deformed into the end-exhale computed tomography image. The D99 and D5 to D95 of the clinical target volume scaled by the prescribed dose with criteria of D99 95% and D5 to D95 5%, V20 for the normal lung, and treatment times were evaluated.Gating windows ≤ ±2 mm fulfilled the CTV criteria for all patients (whereas the criteria were not always met for GWs ≥ ±3 mm) and gave an average reduction in V20 of more than 17.2% relative to free-breathing proton therapy (whereas GWs ≥ ±4 mm resulted in similar or increased V20). The average (maximum) irradiation times were 384 seconds (818 seconds) for the ±1-mm GW, but less than 226 seconds (292 seconds) for the ±2-mm GW. The maximum increased considerably at ±1-mm GW.Real-time-image gated proton beam therapy with a GW of ±2 mm was demonstrated to be suitable, providing good dose distribution without greatly extending treatment time.

Treatment of superficial tumors that move with respiration (e.g. lung tumors) using spot-scanning proton therapy (SSPT) is a high-priority research area. The recently developed real-time image-gated proton beam therapy (RGPT) system has proven to be useful for treating moving tumors deep inside the liver. However, when treating superficial tumors, the proton's range is small and so is the sizes of range straggling, making the Bragg-peaks extremely sharp compared to those located in deep-seated tumors. The extreme sharpness of Bragg-peaks is not always beneficial because it necessitates a large number of energy layers to make a spread-out Bragg-peak, resulting in long treatment times, and is vulnerable to motion-induced dose deterioration. We have investigated a method to treat superficial moving tumors in the lung by the development of an applicator compatible with the RGPT system. A mini-ridge filter (MRF) was developed to broaden the pristine Bragg-peak and, accordingly, decrease the number of required energy layers to obtain homogeneous irradiation. The applicator position was designed so that the fiducial marker's trajectory can be monitored by fluoroscopy during proton beam-delivery. The treatment plans for three lung cancer patients were made using the applicator, and four-dimensional (4D) dose calculations for the RGPT were performed using patient respiratory motion data. The effect of the MRF on the dose distributions and treatment time was evaluated. With the MRF, the number of energy layers was decreased to less than half of that needed without it, whereas the target volume coverage values (D99%, D95%, D50%, D2%) changed by less than 1% of the prescribed dose. Almost no dose distortion was observed after the 4D dose calculation, whereas the treatment time decreased by 26%-37%. Therefore, we conclude that the developed applicator compatible with RGPT is useful to solve the issue in the treatment of superficial moving tumors with SSPT.

Purpose To find the optimum parameter of a new beam control function installed in a synchrotron-based proton therapy system. Methods A function enabling multiple gated irradiation in the flat top phase has been installed in a real-time-image gated proton beam therapy (RGPT) system. This function is realized by a waiting timer that monitors the elapsed time from the last gate-off signal in the flat top phase. The gated irradiation efficiency depends on the timer value, Tw. To find the optimum Tw value, gated irradiation efficiency was evaluated for each configurable Tw value. 271 gate signal data sets from 58 patients were used for the simulation. Results The highest mean efficiency 0.52 was obtained in TW = 0.2 s. The irradiation efficiency was approximately 21% higher than at TW = 0 s, which corresponds to ordinary synchrotron operation. The irradiation efficiency was improved in 154 (57%) of the 271 cases. The irradiation efficiency was reduced in 117 cases because the TW value was insufficient or the function introduced an unutilized wait time for the next gate-on signal in the flat top phase. In the actual treatment of a patient with a hepatic tumor at Tw = 0.2 s, 4.48 GyE irradiation was completed within 250 s. In contrast, the treatment time of ordinary synchrotron operation was estimated to be 420 s. Conclusions The results suggest that the multiple gated-irradiation function has potential to improve the gated irradiation efficiency and to reduce the treatment time.

HLA-B*07:185 differs from B*07:02:01 by one nucleotide substitution in exon 2 at position 300G>C.

Purpose: With the growing adoption of proton beam therapy there is an increasing need for effective and user-friendly tools for performing quality assurance (QA) measurements. The speed and versatility of spot-scanning proton beam (PB) therapy systems present unique challenges for traditional QA tools. To address these challenges a proof-of-concept system was developed to visualize, in real-time, the delivery of individual spots from a spot-scanning PB in order to perform QA measurements. Methods: The PB is directed toward a custom phantom with planar faces coated with a radioluminescent phosphor (Gd2O2s:Tb). As the proton beam passes through the phantom visible light is emitted from the coating and collected by a nearby CMOS camera. The images are processed to determine the locations at which the beam impinges on each face of the phantom. By so doing, the location of each beam can be determined relative to the phantom. The cameras are also used to capture images of the laser alignment system. The phantom contains x-ray fiducials so that it can be easily located with kV imagers. Using this data several quality assurance parameters can be evaluated. Results: The proof-of-concept system was able to visualize discrete PB spots with energies ranging from 70 MeV to 220 MeV. Images were obtained with integration times ranging from 20 to 0.019 milliseconds. If not limited by data transmission, this would correspond to a frame rate of 52,000 fps. Such frame rates enabled visualization of individual spots in real time. Spot locations were found to be highly correlated (R2=0.99) with the nozzle-mounted spot position monitor indicating excellent spot positioning accuracy Conclusion: The system was shown to be capable of imaging individual spots for all clinical beam energies. Future development will focus on extending the image processing software to provide automated results for a variety of QA tests.

We develop a networked data distribution system for broadband seismic waveform data using Java RMI (Remote Method Invocation). Users can download data from various networks using a unified interface. There are two technical problems in building such a user-friendly system with a high capability for expansion: communication through firewalls and information synchronization between request interfaces. We solve these two problems using cgi (common gateway interface) filtering and the Directory Service, respectively. We are now distributing data from various Japanese broadband seismic networks (including PACIFIC21) together with data from BATS (Broadband Array in Taiwan for Seismology) and IRIS through the system. Digital seismic waveform data are being accumulated at an accelerating rate by various networks. Data analysis using these huge data sets is becoming increasingly common. For example, in the Western Pacific region, a large number of digital broadband seismographic stations have recently been installed by various institutions (Figure 1). If the data from these networks are appropriately combined, they effectively constitute a data set from a very dense broadband network. Such a data set should be very useful for determining seismic structure and earthquake source properties with high resolution. However, in the current waveform distribution system, such studies require somewhat tedious procedures for collecting the waveform data from different data centers, each of which has a different user interface. Looking at the field of computer science, distributed object technology (technology for distributing software modules to multiple computers on a network; The Object Management Group, 2000) is one of the most important technologies in modern system-programming practice, as it can handle a huge system in a straightforward manner. Java RMI (Gosling and Steele, 1996; Sun Microsystems, 1999) provides one of the most successful technologies to build a distributed object management system because of its high capability for expansion and security. …

Purpose: To develop a method for treating shallow and moving tumors (e.g., lung tumors) with respiratory-gated spot-scanning proton therapy using real-time image guidance (RTPT). Methods: An applicator was developed which can be installed by hand on the treatment nozzle. The mechanical design was considered such that the Bragg peaks are placed at the patient surface while a sufficient field of view (FOV) of fluoroscopic X-rays was maintained during the proton beam delivery. To reduce the treatment time maintaining the robustness of the dose distribution with respect to motion, a mini-ridge filter (MRF) was sandwiched between two energy absorbers. The measurements were performed to obtain a data for beam modeling and to verify the spot position-invariance of a pencil beam dose distribution. For three lung cancer patients, treatment plans were made with and without the MRF and the effects of the MRF were evaluated. Next, the effect of respiratory motion on the dose distribution was investigated. Results: To scan the proton beam over a 14 x 14 cm area while maintaining the φ16 cm of fluoroscopic FOV, the lower face of the applicator was set 22 cm upstream of the isocenter. With an additional range variance of 2.2 mm and peak-to-peakmore » distance of 4 mm of the MRF, the pencil beam dose distribution was unchanged with the displacement of the spot position. The quality of the treatment plans was not worsened by the MRF. With the MRF, the number of energy layers was reduced to less than half and the treatment time by 26–37%. The simulation study showed that the interplay effect was successfully suppressed by respiratory-gating both with and without MRF. Conclusions: The spot-scanning proton beam was successfully delivered to shallow and moving tumors within a sufficiently short time by installing the developed applicator at the RTPT nozzle.« less

Purpose: To acquire correct information for inside the body in patient positioning of Real-time-image Gated spot scanning Proton Therapy (RGPT), utilization of tomographic image at exhale phase of patient respiration obtained from 4-dimensional Cone beam CT (4D-CBCT) has been desired. We developed software named “Image Analysis Platform” for 4D-CBCT researches which has technique to segment projection-images based on 3D marker position in the body. The 3D marker position can be obtained by using two axes CBCT system at Hokkaido University Hospital Proton Therapy Center. Performance verification of the software was implemented. Methods: The software calculates 3D marker position retrospectively by using matching positions on pair projection-images obtained by two axes fluoroscopy mode of CBCT system. Log data of 3D marker tracking are outputted after the tracking. By linking the Log data and gantry-angle file of projection-image, all projection-images are equally segmented to spatial five-phases according to marker 3D position of SI direction and saved to specified phase folder. Segmented projection-images are used for CBCT reconstruction of each phase. As performance verification of the software, test of segmented projection-images was implemented for sample CT phantom (Catphan) image acquired by two axes fluoroscopy mode of CBCT. Dummy marker was added on the images. Motion of the marker was modeled to move in 3D space. Motion type of marker is sin4 wave function has amplitude 10.0 mm/5.0 mm/0 mm, cycle 4 s/4 s/0 s for SI/AP/RL direction. Results: The marker was tracked within 0.58 mm accuracy in 3D for all images, and it was confirmed that all projection-images were segmented and saved to each phase folder correctly. Conclusion: We developed software for 4D-CBCT research which can segment projection-image based on 3D marker position. It will be helpful to create high quality of 4D-CBCT reconstruction image for RGPT.

Purpose: Spot-scanning technique has been utilized to achieve conformal dose distribution to large and complicated tumors. This technique generally does not require patient-specific devices such as aperture and compensator. The commercially available spot-scanning proton therapy (SSPT) systems, however, cannot deliver proton beams to the region shallower than 4 g/cm2. Therefore some range compensation device is required to treat superficial tumors with SSPT. This study shows dosimetric comparison of the following treatment techniques: (i) with a tabletop bolus, (ii) with a nozzle-mounted applicator, and (iii) without any devices and using intensity-modulated proton therapy (IMPT) technique. Methods: The applicator composed of a combination of a mini-ridge filter and a range shifter has been manufactured by Hitachi, Ltd., and the tabletop bolus was made by .decimal, Inc. Both devices have been clinically implemented in our facility. Three patients with liver tumors close to the skin surface were examined in this study. Each treatment plan was optimized so that the prescription dose of 76 Gy(RBE) or 66 Gy(RBE) would be delivered to 99% of the clinical target volume in 20 fractions. Three beams were used for tabletop bolus plan and IMPT plan, whereas two beams were used in the applicator plan because the gantry angle available was limited due to potential collision to patient and couch. The normal liver, colon, and skin were considered as organs at risk (OARs). Results: The target heterogeneity index (HI = D5/D95) was 1.03 on average in each planning technique. The mean dose to the normal liver was considerably less than 20 Gy(RBE) in all cases. The dose to the skin could be reduced by 20 Gy(RBE) on average in the IMPT plan compared to the applicator plan. Conclusion: It has been confirmed that all treatment techniques met the dosimetric criteria for the OARs and could be implemented clinically.

Purpose: To study the impact of a real-time-image gating on spot scanning proton therapy for lung tumors and to examine the suitable size of the gating window (GW). Methods: We investigated a real-time-image gated proton therapy (RGPT), in which two fluoroscopic units monitor a gold sphere fiducial in real-time, and the proton beam is irradiated only when the marker enters within the pre-assigned GW. We designed 5 treatment plans for 7 lung cancer patients: RGPT with a GW of ±1, 2, 5, and 8 mm and free-breathing proton therapy (FBPT) using the end-exhale and average images of 4-dimensional (4D) CT, respectively. 70 Gy(RBE)/10fr was prescribed to 99% of the targets. The time-series data of the three-dimensional marker positions (RTRT data) were grouped into 10 phases to associate with the phases of 4DCT. The 4D dose distributions were calculated using the plan information, RTRT Data, 4DCT, and modeled accelerator pattern. The dose distribution in each respiratory phase was deformed into the end-exhale CT. The D99 and D5-95 of CTV (with a criteria of D99>95% and D5-95

Purpose: To reduce the lateral penumbra of low-energy proton beams, brass collimators are often used in spot-scanning proton therapy (SSPT). This study investigates the increase in biological effectiveness through collimator scattered protons in SSPT. Methods: The SSPT system of the Hokkaido University Hospital Proton Beam Therapy Center, which consists of a scanning nozzle, a 2-cm thick brass collimator, and a 4-cm thick energy absorber, was simulated with our validated Geant4 Monte Carlo code (ver. 9.3). A water phantom was irradiated with proton pencil beams of 76, 110, and 143 MeV. The tested collimator opening areas (COA) were 5×5, 10×10, and 15×15 cm2. Comparisons were made among the dose-averaged LET values of protons that hit the collimators (LETDColl), protons that did not hit the collimators (LETDNoColl), and all protons (LETDTotal). X-ray equivalent doses (Deq) were calculated using the linear-quadratic model with LETDNoColl and LETDTotal, and their maximum difference was determined over regions where the physical dose was greater than 10% of the peak dose of 2 Gy. Results: The ratio of the dose contribution of collimator scattered protons to that of all protons, defined as λ, was large at high proton energies and large COAs. The maximum λ value ranged from 3% (76 MeV, 5×5 cm2) to 29% (143 MeV, 15×15 cm2). Moreover, a large difference between LETDColl and LETDNoColl was only found in regions where λ was below 20% (ΔLETD > 2 keV/µm) and 8% (ΔLETD > 5 keV/µm). Consequently, the maximum difference between LETDNoColl and LETDTotal was as small as 0.8 keV/µm in all simulated voxels, and the difference of Deq reached a maximum of 1.5% that of the peak dose obtained at the water surface with a 76 MeV beam. Conclusion: Although collimator scattered protons have high LET, they only increase the physical dose, not the biological effectiveness.

Background Even mild perioperative hypothermia is associated with several severe adverse effects. Resistive heating has possible advantages compared with other active warming systems because it can heat several fields independently. To assess this new warming system, we measured core temperature in patients during surgery who were warmed with circulating water mattresses, forced air covers or resistive heating covers. Methods Twenty-four patients undergoing laparoscopic cholecystectomy were randomly assigned to (i) circulating water mattress (38°C), (ii) forced air warming (set to ‘medium’) or (iii) carbon-fibre resistive warming (38°C). Warming was applied throughout anaesthesia and surgery. The groups were compared using one-way ANOVA and Student–Newman–Keuls tests. Results Confounding factors were similar among the groups. Core temperatures in each group decreased for 20 min, but subsequently increased in the forced air and resistive heating groups. There was no significant difference between the forced air and resistive heating groups at any time. In contrast, core temperature in the circulating water group continued to decrease. Consequently, core temperature in the circulating water group was significantly lower than in the other groups 30 min after anaesthetic induction and at later times. Conclusions Resistive heating maintains core body temperature as well as forced air heating and both are better than circulating water. Resistive heating offers the advantage of adjustable heating pods. Br J Anaesth 2003; 90: 689–91

The clinical efficacy of ciprofloxacin was evaluated in 83 patients with chronic respiratory tract infection. Each patient received ciprofloxacin 200 mg TID for 2 or 4 weeks. After 2 weeks of treatment for acute exacerbation of chronic respiratory tract infection, 21 (52.5%) of 40 evaluable patients were considered “improved.” After 4 weeks of treatment, 24 (75%) of 32 evaluable patients were judged “improved.” An additional 2 weeks of treatment increased the rate of improvement. On the other hand, only 6 (23.1%) and 7 (26.9%) of 26 evaluable patients were considered “improved” after 2 and 4 weeks of treatment, respectively, for chronic inflammation. Ciprofloxacin was also administered to 6 patients for more than 60 days to examine its prophylactic effect against acute exacerbation. No patient had an acute exacerbation within 60 days of treatment. Ciprofloxacin is a useful oral antibacterial agent for the treatment and prophylaxis of acute exacerbation of chronic respiratory tract infection.

Purpose: We have developed a gated spot scanning proton beam therapy system with real-time tumor-tracking. This system has the ability of multiple-gated irradiation in a single synchrotron operation cycle controlling the wait-time for consecutive gate signals during a flat-top phase so that the decrease in irradiation efficiency induced by irregular variation of gate signal is reduced. Our previous studies have shown that a 200 ms wait-time is appropriate to increase the average irradiation efficiency, but the optimal wait-time can vary patient by patient and day by day. In this research, we have developed an evaluation system of the optimal wait-time in each irradiation based on the log data of the real-time-image gated proton beam therapy (RGPT) system. Methods: The developed system consists of logger for operation of RGPT system and software for evaluation of optimal wait-time. The logger records timing of gate on/off, timing and the dose of delivered beam spots, beam energy and timing of X-ray irradiation. The evaluation software calculates irradiation time in the case of different wait-time by simulating the multiple-gated irradiation operation using several timing information. Actual data preserved in the log data are used for gate on and off time, spot irradiation time, and time moving to the next spot. Design values are used for the acceleration and deceleration times. We applied this system to a patient treated with the RGPT system. Results: The evaluation system found the optimal wait-time of 390 ms that reduced the irradiation time by about 10 %. The irradiation time with actual wait-time used in treatment was reproduced with accuracy of 0.2 ms. Conclusion: For spot scanning proton therapy system with multiple-gated irradiation in one synchrotron operation cycle, an evaluation system of the optimal wait-time in each irradiation based on log data has been developed. Funding Support: Japan Society for the Promotion of Science (JSPS) through the FIRST Program.

Backgrounds:The first Proton Beam Therapy (PBT) system, which has gated spot scanning with real-time tumor-tracking, has been developed and is now under operation. The new system enables us to deliver highly conformal dose to the moving target tumors while sparing surrounding healthy tissues by integrating real-time tumor-tracking and discrete spot scanning techniques. The system is designed to be spot scanning dedicated in order to maximize the efficiency of proton beam utilization and minimize the size of system and facility. Methods: The newly designed system consists of a synchrotron, beam transport systems, a compact rotating gantry system with robotic couch and two orthogonal sets of X-ray fluoroscopes. The system has the ability to control dose distribution with spot scanning beams and to gate the beams from the synchrotron to irradiate a moving target tumor only when the actual positions of fiducial markers are within the planned positions. The new sophisticated synchrotron control system enables multiple-gated irradiations per operation cycle according to the gating signals of the real-time tumor-tracking system. Investigation has been made to minimize motion dose errors and irradiation times. Both treatment accuracy and efficiency were improved significantly in the new system. Researches for Cone-Beam CT and four-dimensional treatment planning system are work-in-progress to maximize its clinical usefulness. Results: The PBT center started patient treatment in March 2014. Commissioning of the system was finished in November and gated spot scanning treatment has been started from December 2014. Several patients with prostate and liver cancer have been successfully treated. The real-time tumor-tracking system has been demonstrated accurate doze distributions for moving target tumors. Conclusion: The new capability of the PBT for moving tumors has been realized by using the gated spot scanning with real-time tumor-tracking system. The system will deliver significant advantages for both clinical and economical points of view.

Purpose To verify the effect of intrafraction patient repositioning based on real time image guidance on the proton dose distribution for prostate cancer. Methods Dose distributions were simulated using CT images of prostate cancer patients. Treatment plans were prepared using proton beam from left side of the patient with 3 and 6 mm lateral margins. During the beam delivery, prostate position was assumed to be shifted by 5 mm in anterior, posterior, superior and inferior directions. The dose distributions were calculated for two scenarios; (i) the patient position was readjusted by 5 mm just after the prostate shift occurs (ii) the patient position was not adjusted. Such a real time readjustment can be realized with real time image guidance. The differences of the values D5 and D95 in CTV (D5–95) were compared between different sizes of the lateral margins and different scenarios. Results D5–95 values in the case of scenario (i) are smaller than scenario (ii). The differences between scenario (i) and (ii) were not depend on the directions of the prostate shift. In the case of scenario (ii), margin expansion makes D5–95 values small. In the case of scenario (i), margin size is uncorrelated to D5–95 values. Conclusion These results indicate that the intrafraction patient repositioning is effective to minimize dose deterioration when the prostate moves during the irradiation. In the case without intrafraction patient repositioning, margin expansion is effective to reduce dose deterioration. In the case with intrafraction patient repositioning, 3 mm margin is enough to minimize dose deterioration.

Aims: The prognosis of non-small cell lung cancer with pathologic mediastinal lymph node involvement (pN2) is poor, we wished to study the expression of p53, bcl-2 by immunohistochemistry in a series of such patients. Methods: Clinicopathologic factors were investigated in relation to prognosis in 60 patients with resected pN2 non-small cell lung cancer. Results: The 5-year survival rate was 21.7%. Positive staining for p53, and bcl-2 was found in 29/60 and 12/60, respectively. Patients with bcl-2 positive tumor had a more favorable survival than those with bcl-2 negative tumor ( P =0.0054). The expression of p53 was not related to patients' survival. Multivariate analysis showed that Bcl-2 expression and single N2 station were independent prognostic factors. Conclusions: Patients with bcl-2 positive tumors may comprise a favorable prognostic subgroup in pN2 non-small cell lung cancer.

High-power, high-switching-frequency amplifiers have been developed for stabilizing the m=2/n=1 MHD (magnetohydrodynamic) mode of plasma in the JFT-2M to avoid plasma disruptions. The amplifiers are a set of two inverters (INV 1 and INV 2). Each inverter has a current of 1500 A, a voltage of 500 V, and a switching frequency of 20 kHz. The component device of the inverter is an IGBT (insulated gate bipolar transistor) MG300N1US1. Each inverter has three bridges composed of eight IGBTs with eight high-speed free-wheeling diodes, respectively. Controllers of the inverters are made by the PWM (pulse width modulation) method and directly operated by voltage references E/sub c/. In the test operations, each inverter operated in the switching frequency of 20 kHz, and the maximum sine-wave current of +1500 A--1500 A at the 60-Hz reference signals. >

The first experiment on the Nb-Ti pulsed coils, DPC (demonstration poloidal coil)-U1 and -U2, was successfully performed. The coils have a cable-in-conduit conductor cooled by 4-K supercritical helium, and their windings have 1-m inner, and 2-m outer, diameters. Charging tests on the coils were performed in both DC and pulsed modes. In DC mode, the coils were charged individually to their design current of 30 kA, and attained a peak field of 5.2 T and a stored energy of 11 MJ. In pulsed mode, using the power supply of the JT-60, the designed pulsed field of 7 T/s were achieved by charging one of the two coils to its design current in 0.75 s. AC losses of the coil during the pulsed operation were confirmed to be quite small. Mechanical, thermal, and hydraulic properties were also analyzed on the basis of the experimental results. >

A direct current interrupting system for large superconducting magnets has been developed with a new idea. It is successful to make the system compact and reliable by using an iron core. Simulations and model tests were performed in order to prove the idea. Finally a DC interrupting system can be designed in a practical size.

Objective. To determine whether elevations in serum leucine aminopeptidase (LAP) levels reflected the underlying evolution of active disease in systemic lupus erythematosus (SLE). Methods. We studied serum LAP levels, other laboratory indicators, and SLE Disease Activity Index (SLEDAI) scores, in 46 consecutive patients with SLE admitted to Tokyo Metropolitan Komagome Hospital. LAP levels in 46 patients with rheumatoid arthritis were also measured. Results. Thirty-three SLE patients had elevated LAP levels. LAP levels correlated positively with levels of lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase and γ-glutamyl transpeptidase, and negatively with the total serum haemolytic complement and leucocyte, neutrophil and lymphocyte counts, but showed no correlation with alkaline phosphatase, γ-globulin, β 2 -microglobulin or C-reactive protein levels, or platelet count. The SLEDAI score correlated positively with LAP levels. The LAP level in patients with rheumatoid arthritis was near normal. Conclusion. The serum LAP level may be a potential activity indicator for SLE.

Using the database consisting of 236 R/C column specimens conducted in Japan, the characteristic behaviors of strengthening by fiber wrapping were analyzed. The following findings were obtained: (1) The amount of shear reinforcement, the span to depth ratio, the axial compressive stress level influence on the strength and deformation capacities of retrofitted columns by fiber sheet wrapping (2) Shear strength of retrofitted columns can be predicted by previous design equations based on the strut and tie models as same as for usual R/C columns, in which the effective fiber strains of about 1% is appropriate. (3) There are few test data about the confining effect of fiber sheet wrapping on bond resistance of longitudinal bars. Further research effort is required to evaluate the shear strength of columns governed by the splitting of cover concrete along longitudinal bars. (4) The ductility ratio can be roughly estimated as a function of the shear to flexural stress ratio. (5) For the specimens with plain round longitudinal bars, the previous equations based on the strut and tie model cannot be applied because of the poor bond capacity.

The research on seismic retrofit of RC members using continuous fiber sheets is rapidly advancing in Japan. These research activities have been accelerated since the Hanshin-Awajii Earthquake, 1995 becasue this retrofitting technique has an advantage due to lightweight, flexibility, non-welding, and easy handling in construction works. The most preferable retrofitting technique for the existing building being in use is jacketing RC columns with carbon or aramid fiber sheets because of the advantage above. Recently many results of the research on short column with spandral wall, columns with wing wall, beams with slab (T shaped beam), earthquake resisting wall have been reported in Japan. This paper introduces, first of all, these experimental research results in detail and the seismic retrofitting effects by the continuous fiber sheets are comprehensively evaluated. Flexural capacity, shear capacity and the improvement of ductility are discussed to evaluate the effect of reinforcement of continuous fiber sheets. Then, methods for evaluating the seismic retrofit of regular columns with continuous fiber sheets are described. A basic idea of the evaluation method proposed for a regular column is shown, and the problems which should be examined are extracted and explained about these effects. As the summary, the problems which should be solved, research direction and prospect are pointed out for the future research on seismic retrofit by continuous fiber sheets. Research needs for establishment of a design method when various members are reinforced by continuous fiber sheets in the future are also discussed.

Since the 1995 Hansin Earthquake, need of seismic retrofitting of existing structures has been strongly understood. Being expected to reduce inconvenience in retrofit work of buildings, some techniques using carbon and/or aramid fibers have been widely employed in Japan due to lightweight, flexibility, non-welding, and easy handling. Many of these techniques aim to improve shear capacity and ductility of existing reinforced concrete columns and may be called "Standard Method" due to the almost common working procedure. The procedure includes (1) wrapping columns in the transverse direction using continuous fiber sheets, (2) impregnating epoxy resin into the sheets to make FRP composite, and (3) doing surface treatment or arrangement of concrete to prevent voids or wrinkles. This "Standard Method" of fiber wrapping has induced development of other methods that improve a working process or can be applied for other structural members. In the future, the fiber wrapping technique will be more spread, however, it requires an approved and common quality control method. An education program for retrofit engineers and craftsmen should be also established.

This research aims on understanding the influence of the method using carbon fiber reinforced plastic (CFRP) sheets on the performance of 13 reinforced concrete columns with waist-high walls. Main parameters of the specimens include the thickness and height of the attached walls, axial load, and the amount of CFRP sheets. The strengthening method is done by wrapping the upper portion of the column with sheets in a closed form. Also, the waist-high walls are equipped with holes where the carbon fiber strands (CF-anchor) are inserted and anchored to the ends of the sheets attached only on the surface of the lower portion of the column. Test results show that there is a great improvement in the ductility of the shear-failure type specimens when strengthened with CFRP. Also with an increase in the amount of the sheets, the ductility is further enhanced. The specimens strengthened using CFRP with CF-anchor also show higher ductility than the specimen where only the upper column is strengthened. The bending and shear strengths of the columns with waist-high walls can be calculated by using effective column height h(e) considering the presence of the all portions.

Cytokines such as interleukins are known to be involved in the development of neuropathic pain through activation of neuroglia. However, the role of chemokine (C-C motif) ligand 1 (CCL-1), a well-characterized chemokine secreted by activated T cells, in the nociceptive transmission remains unclear. We found that CCL-1 was upregulated in the spinal dorsal horn after partial sciatic nerve ligation. Therefore, we examined actions of recombinant CCL-1 on behavioural pain score, synaptic transmission, glial cell function and cytokine production in the spinal dorsal horn. Here we show that CCL-1 is one of the key mediators involved in the development of neuropathic pain. Expression of CCL-1 mRNA was mainly detected in the ipsilateral dorsal root ganglion, and the expression of specific CCL-1 receptor CCR-8 was upregulated in the superficial dorsal horn. Increased expression of CCR-8 was observed not only in neurons but also in microglia and astrocytes in the ipsilateral side. Recombinant CCL-1 injected intrathecally (i.t.) to naive mice induced allodynia, which was prevented by the supplemental addition of N-methyl-𝒟-aspartate (NMDA) receptor antagonist, MK-801. Patch-clamp recordings from spinal cord slices revealed that application of CCL-1 transiently enhanced excitatory synaptic transmission in the substantia gelatinosa (lamina II). In the long term, i.t. injection of CCL-1 induced phosphorylation of NMDA receptor subunit, NR1 and NR2B, in the spinal cord. Injection of CCL-1 also upregulated mRNA level of glial cell markers and proinflammatory cytokines (IL-1β, TNF-α and IL-6). The tactile allodynia induced by nerve ligation was attenuated by prophylactic and chronic administration of neutralizing antibody against CCL-1 and by knocking down of CCR-8. Our results indicate that CCL-1 is one of the key molecules in pathogenesis, and CCL-1/CCR-8 signaling system can be a potential target for drug development in the treatment for neuropathic pain.

The effect of alcohol ingestion on learning disturbances was tested in rats. Rats were fed either an alcohol solution or a nonalcohol solution. The concentration of acetylcholine in the whole brain was significantly lower in rats fed with alcohol than rats fed without alcohol. Passive avoidance learning shows a lower tendency in rats with alcohol compared to rats without alcohol, but the alcohol and control groups did not differ in passive avoidance learning. We suggest that alcohol may disturb acetylcholine metabolism in the brain.

The effect of nicotine on learning disturbances was tested in rats. Rats were fed either a choline-enriched or a choline-deficient diet. Concentration of acetylcholine in the whole brain was significantly lower in rats fed with choline-deficient diet than rats fed with choline-enriched diet. Passive avoidance learning shows that rats on a choline-deficient diet showed significantly impaired learning compared to rats on a choline-enriched diet. Nicotine (0.04 mg/kg) administered intraperitoneally significantly potentiated learning in rats on a choline-deficient diet, as well as in rats on a choline-enriched diet. We, therefore, suggest that nicotine may potentiate learning in an acetylcholine-deprived brain.

As development of superconducting pulse poloidal coils for tokamak fusion machines, a Nb3Sn Demo Poloidal Coil(DPC-EX) has been fabricated and tested. The DPC-EX, whose inner diameter is 1 m, consists of two-double pancakes made by a react-and-wind technique. The conductor is a forced cooled flat cable-in-conduit conductor. The DPC-EX has been installed between the DPC-U1 and U2 and tested with various operation modes. Under the operation mode connected with the U1, U2 in series, the DPC-EX has been ramped up to 17 kA in 1 s and ramped down to zero in 1 s after a flat top time for 1 s. The magnetic field was 6.7 T and the pulsed field was 6.7 T/s, respectively. The current density in winding was 37.2 A/mm2. The ratio of ac loss to stored energy was about 0.14%.

The authors propose a self-learning strategy for robot vision systems which are used to identify the position of the target part handled by a robot. They tried to use a neural network as a decision-making system which determines how to move the robot to reach the exact target on the base of the image acquired by the robot eye. The authors taught this function automatically to the neural network. The total system works as follows: (1) a target object is set at a known position, and the position is taught to the system, (2) the robot moves randomly around the target and the neural network learns the relation between the relative positions and images, and (3) after enough learning, the robot can identify the target located at an arbitrary position. >

[Background and Aims] The role of hepatitis C virus (HCV) for prediction of the effect of interferon (IFN) therapy is known to many investigations. However, there is available reports on complete response with IFN therapy for predictive factors between characteristics of patients and HCV. Recently, high dose IFN treatment is known to more effective to elevate the eradication rate of HCV in Japan. The alms of the present study is to elucidate the effect of high dose natural IFN-ct (human lymphoblastoid IFN-ct: derived BALL-l) treatment and to analyze predictive factors with the multivariate cox proportional hazard model. [Methods] 215 patients with chronic hepatitis C (153 males and 62 female, mean age 49.9 years) were treated with only 10MU of high dose natural IFNct (OIF-Otsuka Pharma. Co. Ltd.) by intramuscular injection daily for 2 or 4 weeks, followed by three times a week for 20 or 22 weeks; all patients completely agreed to take part in this study. A complete responder was defined as HCV-RNA negative by the end of treatment (24weeks). At an aspect of virus, predictive factors of virus load and genotype were determined by PCR. At an aspect of patient's background, ALT, AST and Platelets were measured by serum samples. All parameters were tested by the multivariate cox proportional hazard model. Data analysis was performed with the computer program SAS jump. [Results] One hundred and twenty five of 215 with genotypelb patients, 51 with genotype2a, and 28 genotype2b patients were included. 140 of 215 patients had more than 106 copies/ml. 48 in 140 patients were responded well, totally 89 in 215 (41.4%). There was no serious adverse effect in all the treated patients. Results of the multivariate cox proportional hazard model are shown in the table below.

A specially-developed multidisplay system using a 6 inch color CRT, created through actual testing in experimental vehicles, was mass-produced for the Japanese market in January 1985. A year later, the multidisplay system was improved through an addition in the information displayed on the CRT and mounted in the 1986 Toyota Soarer. These improvements are described, and an outline of the multidisplay system and details regarding newly developed technology consequent to its development are also described. >

Revue des publications sur ce sujet. Description de la determination des spectres de reponse sismique a partir des enregistrements des mouvements du sol

The memory is organized as 8192 words/spl times/8 bits. A memory cell consists of a programmable element composed of a p-n junction diode and a vertically connected p-n-p transistor. During programming, the programmable element is changed from the current-blocking state of a reverse diode to the current-conducting state of a shorted junction diode by using the diffused eutectic aluminum process (DEAP). With a selective power switching dual-stage decoder, the power dissipation in the decoder circuit was reduced to 40% of a conventional decoder without power switching. The power saved was used to speed up the multiplexers and the output buffers.