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Purpose: A commercial 6D carbon fiber radiotherapy treatment couch (Imaging Couch Top, BrainLAB) has recently been reported to attenuate photon beams and increase skindose. To prevent skin toxicity and ensure the target dose, it is important to correct the attenuation properties of the treatment couch with the treatment planning system (TPS). In this study, we evaluated the accuracy of dose attenuation correction by a virtual couch technique integrated into the TPS. Methods: A virtual couch was modeled in the TPS (Eclipse v10.0, Varian). The CT value of the virtual couch was assigned with the CT value of the kilovoltage‐CT images of the treatment couch. A phantom consisting of several plastic water slabs was created. We selected an evaluation point within the phantom on the couch structure at a 9 cm depth from the couch surface, which was placed at the isocenter. The doses at this point were calculated and measured at several gantry angles, from 120 degree to 240 degree at 10 degree steps, and each field size was 10 cm × 10 cm. The prescribed dose was 100 monitor units for 6/10 MV photon beams and 6 MV‐SRS mode (Trilogy Tx, Varian). Dose measurements were performed with an ion chamber.Results: The largest difference between measured and calculated doses was 3.3% for a gantry angle of 120 degree and 6 MV‐SRS mode. The average dose difference was within 1.6% for all gantry angles and photon beams. In the case without attenuation correction, the largest difference was 8.2% and the average difference was 5.2%. Conclusions: Use of the virtual couch technique in TPS accomplished sufficient accuracy for dose attenuation correction of the 6D carbon fiber treatment couch, and it is an effective method for clinical use.

In acute glufosinate poisoning, sudden respiratory arrest and convulsion can occur after a latent period of 4-60 h. There is still no factor that accurately predicts the occurrence of these symptoms.To elucidate the predictors of severe effects following acute glufosinate poisoning.This study is a retrospective observational case series. The subjects were 16 patients who had acute glufosinate poisoning. They were divided into a group with respiratory arrest or convulsion during hospitalization (severe group) and a group without (non-severe group). The following characteristics (or predictors) were compared between the groups: age, sex, calculated amount of glufosinate (volume of ingested poison (glufosinate-containing herbicide) × glufosinate concentration of the product), time duration from poison ingestion to arrival at our hospital, use of gastric lavage, use of whole bowel irrigation, Glasgow Coma Scale, laboratory parameters, PaO₂/FiO₂ ratio (P/F ratio), shock index, and presence or absence of systemic inflammatory response syndrome (SIRS) on arrival.The P/F ratio was significantly lower in the severe group than in the non-severe group (median, 287.5 vs. 409.0; P = 0.049). The receiver operating characteristic (ROC) curve was plotted for the predictor of increasing severity based on the P/F ratio. The area under the curve was 0.714, and the optimal cutoff point for increasing severity was 374.0. The sensitivity was 75.0%, specificity of 71.4%, and accuracy of 75.0%. The shock index was significantly higher (median, 0.52 vs. 0.41; P = 0.031). Significantly more patients had SIRS in the severe group than in the non-severe group (P = 0.015). Logistic regression analysis was performed with a backward elimination procedure. SIRS was selected as the independent predictor of increasing severity (odds ratio, 29.810; 95% confidence interval, 1.011-878.952; P = 0.049).Severe effects following acute glufosinate poisoning were associated with two positive SIRS criteria. A low P/F ratio may be useful for predicting the occurrence of respiratory complications.

Objective: This study was designed to establish a rat model of a critical size alveolar bone defect. Materials and methods: Standardized buccal or mesiobuccal alveolar bone defects were made around the right first mandibular molar of 12-week-old rats, and the left was used as a control. Alveolar bone healing was examined quantitatively by three-dimensional micro-computed tomographic imaging. Bone matrix production of osteoblasts and osteocytes during repair of alveolar bone defects was examined with in situ hybridization for type I collagen. Results: Buccal defects were repaired significantly and the volume decreased by 88.3% in week 24, whereas mesiobuccal defects were repaired little. Osteoblasts and osteocytes expressed type I collagen in both defects in week 3 but showed little expression by week 6 and thereafter, leaving the mesiobuccal defects largely unrepaired. Conclusion: The mesiobuccal defect is a critical-size defect that is not ultimately repaired with bone. It may be an appropriate experimental model for investigating the effectiveness of bone regenerative agents in human alveolar bone loss.

A data mining method is proposed for extracting feature regions and for suggesting design candidates from large-scale Computational Fluid Dynamics (CFD) results. The de- tected regions in this method are the regions where the pressure difference between the front and back sides is large. We introduce a medial-surface used in the structural analysis for the thin parts as an evaluation surface in order to apply complicated geometries, which have curved surfaces, holes, ribs, and steps. We applied this method to the laser diode (LD) cool- ing problem in optical disc drives, and the following results were obtained. (1) Three feature- regions are extracted from the CFD results. (2) Two of three regions were effective and were consistent with the actual product design.

We have irradiated p-on-n silicon microstrip detectors of initial bulk resistivity between 0.2 and 2.7 k/spl Omega/-cm with 55 MeV protons to fluences of 0.8, 2.2 and 11/spl times/10/sup 13/ p/cm/sup 2/ (equivalent to twice the fluence in high energy protons), and have measured the depletion voltage before and after irradiation using C-V methods. In addition, we have measured the charge collection of minimum ionization on a single strip with a fast amplifier as a function of bias voltage. We compare the depletion voltage deduced from both methods for samples with different initial resistivities.

Ten patients with adenosine deaminase deficiency (ADA−) have been enrolled in gene therapy clinical trials since the first patient was treated in September 1990. We describe a Japanese ADA− severe combined immune deficiency (SCID) patient who has received periodic infusions of genetically modified autologous T lymphocytes transduced with the human ADA cDNA containing retroviral vector LASN. The percentage of peripheral blood lymphocytes carrying the transduced ADA gene has remained stable at 10% to 20% during the 12 months since the fourth infusion. ADA enzyme activity in the patient's circulating T cells, which was only marginally detected before gene transfer, increased to levels comparable to those of a heterozygous carrier individual and was associated with increased T-lymphocyte counts and improvement of the patient's immune function. The results obtained in this trial are in agreement with previously published observations and support the usefulness of T lymphocyte-directed gene transfer in the treatment of ADA−SCID.

Aim: IRIS is one of the standard regimens as second line treatment in mCRC since IRIS demonstrated the non-inferiority to FOLFIRI (FIRIS study) in Japan. From the results of 20050181 trial, FOLFIRI/panitumumab significantly improved PFS and is well-tolerated as second-line treatment in patients with KRAS wild type of mCRC. Thus we conduct the study of IRIS/Cet (HGCSG0902). Methods: HGSCG0902 is a multicenter phase ll study. Eligibility includes histologically confirmed colorectal cancer, previously received oxaliplatin-contained chemotherapy, PS: 0-1, EGFR positive and KRAS Exon2 wild type. Patients (pts) received S-1 80-120 mg/day p.o. on days 1-14 and irinotecan 100mg/m2 on days 1 and 15 repeated every 28 days. Cetuximab was administrated 400mg/m2 loading dose and continued 250mg/m2 every week or 500mg/m2 bi-weekly. The primary endpoint was response rate and the secondary endpoints were disease control rate, PFS, OS and safety. We estimated that a target sample size of 76 patients. Results: Between Mar 2010 and September 2013, 58 pts were enrolled. One patient was not administered (57 pts were safety analysis set), and 3 pts were ineligible (54 pts were efficacy analysis set). Patients characteristics were as follows: median age 66 years (range 35-79), Male: female 36:21, PS 0:1 38:19. Median number of cycles was 3. The main grade 3-4 AE were diarrhea (35.1%), neutropenia (26.8%), acne like rash (17.5%) and anorexia (15.8%). The median relative dose intensity of IRIS/Cet was 0.818. Response rate was 33.3% (95%CI 20.8-45.9%) and disease control rate was 79.6%. Median progression-free survival was 4.7 months (95%C.I. 3.3-6.1 months). Conclusions: IRIS/Cet appeared to be highly effective with a response rate of 33.3% and progression-free survival of 4.7 months, and had met the primary endpoint. Diarrhea was a major adverse event, but was manageable by dose reduction and supportive care. The final analysis will be presented in 2015 ASCO Annual meeting. Disclosure: S. Yuki: Taiho Pharmaceutical, Chugai Pharmaceutical, Bristol-Myers Squibb, Merck Serono, Takeda Pharmaceutical, Yakult Honsha;M. Nakamura: Takeda Pharmaceutical, Chugai Pharmaceutical, Bayer Yakuhin;Y. Tsuji: Honoraria - Ono Pharmaceutical; Y. Sakata: Taiho Pharmaceutical, Daiichi Sankyo, Yakult Honsha, Otsuka Pharmaceutical, Merck Serono, Bristol-Myers Squibb, Synergy International; Y. Komatsu: Yakult Honsha, Taiho Pharmaceutical, Chugai Pharmaceutical, Merck Serono, Pfizer Japan, Novartis Pharma, Sawai Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, Eli Lilly Japan, Kureha Corporation. All other authors have declared no conflicts of interest.

Aim: Panitumumab (Pmab) has demonstrated efficacy in patients with KRAS wild-type metastatic colorectal cancer (mCRC). Although the STEPP study (Lacouture M. E. et al. J Clin Oncol. 2010; 28: 1351-7.) showed that pre-emptive skin treatment reduced skin toxicities compared with reactive treatment among patients receiving Pmab, data for Asians has not been reported. We planned a randomized, open-label trial to verify the differences between pre-emptive and reactive treatment for skin toxicities in Japanese patients. Methods: Patients receiving third-line Pmab-containing regimens for mCRC were randomly assigned 1:1 to pre-emptive (skin moisturizers, sunscreen, topical steroid, and minocycline) or reactive (only skin moisturizers) skin treatment. The primary endpoint was the cumulative incidence of ≥grade 2 skin toxicities during the 6-week treatment period. Retrospectively, a dermatologist reviewed skin toxicities, in a blinded manner, using photographs. Results: Of 95 enrolled patients, 47 were assigned to pre-emptive, and 48 to reactive treatment. The incidence of ≥grade 2 skin toxicities during the 6-week treatment period (investigators’ assessment) was 21.3% and 62.5% (risk ratio [RR], 0.34; 95% CI, 0.19 to 0.62; P Conclusions: Although pre-emptive skin treatment could not be affected with QOL, it could reduce the severity of skin toxicities during Pmab treatment. Our data clearly validate that pre-emptive treatment can also be recommended in Japanese patients. Disclosure: M. Nakamura: Takeda Pharmaceutical, Chugai Pharmaceutical, Bayer Yakuhin; S. Yuki: Taiho Pharmaceutical, Chugai Pharmaceutical, Bristol-Myers Squibb, Merck Serono, Takeda Pharmaceutical, Yakult Honsha; Y. Sakata: Taiho Pharmaceutical, Daiichi Sankyo, Yakult Honsha, Otsuka Pharmaceutical, Merck Serono, Bristol-Myers Squibb, Synergy International; Y. Komatsu: Yakult Honsha, Taiho Pharmaceutical, Chugai Pharmaceutical, Merck Serono, Pfizer Japan, Novartis Pharma, Sawai Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, Eli Lilly Japan, Kureha Corporation. All other authors have declared no conflicts of interest.

Recently generated knockout mice with disrupted genes encoding endothelin (ET)-1 showed an elevation of arterial blood pressure (AP) and supplied an evidence for intrinsic ET-1 as one of the physiological regulators of systemic AP. Little is yet known, however, why deficiency of ET-1, which was originally found as a potent vasoconstrictor, led to higher AP in these mice. To address this apparent paradox, we first developed a method to measure renal sympathetic nerve activity (RSNA) in mice using rats as reference and successively compared it between normal and ET-1 deficient mice. RSNA was successfully recorded in urethane-anesthetized and artificially ventilated mice by a slight modification of the method used for rats. At basal condition, mean AP (MAP) and RSNA in ET-1 deficient mice (105+/-2 mmHg and 9.71+/-1.49 muVs, n=20) were significantly higher than those in wild-type mice (96+/-2 mmHg and 5. 07+/-0.70 muVs, n=25). Basal heart rate (HR) and baroreflex-control of HR was not significantly different between the two. On the other hand, resting RSNA, RSNA range, and maximum RSNA were significantly greater in ET-1 deficient mice, and thus MAP-RSNA relationship was upwards reset. Hypoxia-induced increase in RSNA was not different between ET-1 deficient (73.4+/-9.4%) and wild-type mice (91.2+/-12.0%), while hypercapnia-induced one was significantly attenuated in ET-1 deficient mice (18.8+/-3.6 vs. 39.1+/-5.2% at 10% CO2). These results indicate that endogenous ET-1 participates in the central chemoreception of CO2 and reflex control of the RSNA. Baroreceptor resetting and normally preserved hypoxia-induced chemoreflex may explain a part of the elevation of AP in ET-1 deficient mice.

Three cases of X-linked auto-immune enteropathy with haemolytic anaemia and polyendocrinopathy are described from one related Japanese kindred. Two boys had died due to severe diarrhoea accompanied by total or subtotal intestinal villous atrophy. In contrast, although one patient showed the same symptoms and had circulating IgG antibodies against enterocytes, his condition improved dramatically and he developed well following the use of cyclosporin A (CSA). CSA may be beneficial in patients with this rare disorder. Auto-immune enteropathy should be considered as a cause of protracted diarrhoea with unknown aetiology.

A reflective multicolor matrix LCD with micro color filters is investigated. In order to improve the brightness of the LCD, contrast and brightness of various liquid-crystal display modes are analyzed. This analysis suggests the choice of the phase-change-type guest-host mode. The optimal parameters for this mode are derived. In addition, the transmission spectrum of the micro color filters is investigated and the optimal doping concentration of the dye in the color filters is determined. This results in a reflective color LCD with acceptable brightness.

A novel single-chip LSI circuit for National Television System Committee color TV (NTSC CTV) signal processing is described. The circuit covers the entire range of TV chassis. The number of external components and PCB (printed circuit board) area can be reduced to approximately 60% of those for a conventional set. The circuit will contribute to the upgrading of standard TV chassis by saving PCB area and increasing the reliability of sets. The circuit integrates 3980 linear elements, a 1200-pF capacitor, and 590 gates on a 5.1*4.5 mm/sup 2/ chip with a shrink 54-pin dual-in-line package (DIP). >

The relationship between the degree of exposure and biological effects of acrylonitrile (AN) was studied in 102 workers whose exposure period exceeded five years, and in 62 matched controls, all of whom had been randomly sampled from six acrylic fibre factories in Japan. The six factories were classified into three groups on the basis of AN concentration at workplaces. The most highly exposed group of subjects showed an eight-hour average AN concentration of 4-2 ppm by personal sampling, a mean urinary AN concentration of 360 microgram/1 and a mean urinary thiocyanate concentration of 11-4 mg/1. Medical examination, including the indocyanine green excretion test and multiple clinical chemistry determinations, failed to detect any health effect attributable to AN. Slight liver damage may possibly occur in more highly exposed workers. Urinary AN and thiocyanate determinations may provide more accurate estimates of low-grade exposure (less than 5 ppm).