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Abstract: In order to confirm the possibility that hydrogen in Ta film migrates during SIMS measurement, the influence of primary ion beam irradiation conditions on the depth profile of hydrogen in a Ta film was investigated. Deuterium implanted in a Ta2O5/Ta/Ta2O5 structure was analyzed using Cs+ irradiation interruption. The result shows that hydrogen was discharged from the Ta film to the vacuum of the sample chamber during SIMS measurements with a Cs+ ion beam. The deuterium profile of the Ta film analyzed with an O2 + primary ion beam differed from those with Cs+ or Ar+ irradiations, and it depended on the incidence angle of the O2 + beam. According to these results, we propose a model where the hydrogen is discharged from Ta films to the vacuum of the sample chamber when Ta2O5 film is removed with Cs+ or Ar+ beam irradiation, but the hydrogen is not discharged when Ta2O5 film is formed on the Ta surface using O2 + primary beam irradiation. [Copyright &y& Elsevier]

We have measured performance of a lead/plastic scintillator sampling calorimeter in two separate beam tests at low (1–4 GeV) and high (10–200 GeV) energies. The calorimeter is composed of 8-mm-thick lead plates and 2-mm-thick plastic scintillator plates for hardware compensation, where responses to electromagnetic and hadronic showers of the same energy are identical. We find the linearity to be better than 1% in the energy range between 2 and 150 GeV for both pions and electrons. The energy resolutions are obtained to be (46.7±0.6)%/√ of E⊕(0.9±0.9)% for pions, where the energy E is given in GeV. The response ratio of electromagnetic showers to hadronic showers is measured to be 1.04±0.01 at low energies, and 0.99±0.01 at high energies. [Copyright &y& Elsevier]

Background and Purpose: Alogliptin, a highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor, enhances incretin action and pioglitazone enhances hepatic and peripheral insulin actions. Here, we have evaluated the effects of combining these agents in diabetic mice.Experimental Approach: Effects of short-term treatment with alogliptin alone (0.01%-0.1% in diet), and chronic combination treatment with alogliptin (0.03% in diet) and pioglitazone (0.0075% in diet) were evaluated in db/db mice exhibiting early stages of diabetes.Key Results: Alogliptin inhibited plasma DPP-4 activity up to 84% and increased plasma active glucagon-like peptide-1 by 4.4- to 4.9-fold. Unexpectedly, alogliptin alone lacked clear efficacy for improving glucose levels. However, alogliptin in combination with pioglitazone clearly enhanced the effects of pioglitazone alone. After 3-4 weeks of treatment, combination treatment increased plasma insulin by 3.8-fold, decreased plasma glucagon by 41%, both of which were greater than each drug alone, and increased plasma adiponectin by 2.4-fold. In addition, combination treatment decreased glycosylated haemoglobin by 2.2%, plasma glucose by 52%, plasma triglycerides by 77% and non-esterified fatty acids by 48%, all of which were greater than each drug alone. Combination treatment also increased expression of insulin and pancreatic and duodenal homeobox 1 (PDX1), maintained normal beta-cell/alpha-cell distribution in islets and restored pancreatic insulin content to levels comparable to non-diabetic mice.Conclusions and Implications: These results indicate that combination treatment with alogliptin and pioglitazone at an early stage of diabetes improved metabolic profiles and indices that measure beta-cell function, and maintained islet structure in db/db mice, compared with either alogliptin or pioglitazone monotherapy. [ABSTRACT FROM AUTHOR]

Here, we apply 20 MeV particle-induced X-ray emission (PIXE) to elemental analysis of microplastic samples with a diameter of approximately 2 mm, collected from the seashores of the northeastern area of Honshu in Japan. The samples were in a grain form with unwanted elements adhering to their surfaces. The PIXE measurements were conducted in a helium atmosphere. For normalization, the number of K X-rays of the residual gas argon was used instead of the directly measured beam irradiation, and the number of continuous X-rays in the PIXE spectrum was used instead of the mass of each sample. Thirteen elements were identified on the microplastics, among which were toxic chromium and lead. Thus, PIXE analysis is useful for analyzing microplastic samples. [ABSTRACT FROM AUTHOR]

Perioperative chemotherapy (CT) and chemoradiotherapy are widely used for advanced esophageal cancer. We evaluated the chemosensitivity of patients displaying recurrent esophageal cancer after esophagectomy with perioperative CT. From the database at National Cancer Center Hospital in Tokyo, we extracted recurrent esophageal cancer cases after perioperative CT and evaluated the effectiveness of the first CT against the recurrent disease according to the duration between termination of the original perioperative CT and recurrence with treatment-free intervals (TFIs) ≤6 and >6 months. Systemic CT for their recurrent disease was performed for 30 esophageal cancer patients after perioperative CT. All patients received 5-fluorouracil and cisplatin as perioperative CT, with relapses occurring at TFIs ≤6 months in 11 patients (eight received platinum-containing regimens and three received docetaxel for their recurrent disease) and >6 months in 19 patients (all received platinum-containing regimens). The response rate of patients experiencing a recurrence at TFIs ≤6 and >6 months was 0 and 37% ( P = 0.029), the median progression-free survival was 2.8 and 4.8 months (log-rank P = 0.001) and the median overall survival was 6.1 and 10.2 months (log-rank P = 0.012), respectively. Recurrence at the TFI ≤6 months could represent resistance to CT, so regimens may need to be altered depending on a patient's specific TFI. [ABSTRACT FROM AUTHOR]

We compared the efficacy and the safety of a carboplatin plus etoposide regimen (CE) vs split doses of cisplatin plus etoposide (SPE) in elderly or poor-risk patients with extensive disease small-cell lung cancer (ED-SCLC). Eligibility criteria included: untreated ED-SCLC; age 70 and performance status 0–2, or age <70 and PS 3. The CE arm received carboplatin area under the curve of five intravenously (IV) on day 1 and etoposide 80 mg m−2 IV on days 1–3. The SPE arm received cisplatin 25 mg m−2 IV on days 1–3 and etoposide 80 mg m−2 IV on days 1–3. Both regimens were given with granulocyte colony-stimulating factor support in a 21–28 day cycle for four courses. A total of 220 patients were randomised. Median age was 74 years and 74% had a PS of 0 or 1. Major grade 3–4 toxicities were (%CE/%SPE): leucopenia 54/51, neutropenia 95/90, thrombocytopenia 56/16, infection 7/6. There was no significant difference (CE/SPE) in the response rate (73/73%) and overall survival (median 10.6/9.9 mo; P=0.54). Palliation scores were very similar between the arms. Although the SPE regimen is still considered to be the standard treatment in elderly or poor-risk patients with ED-SCLC, the CE regimen can be an alternative for this population considering the risk–benefit balance.British Journal of Cancer (2007) 97, 162–169. doi:10.1038/sj.bjc.6603810 www.bjcancer.com Published online 19 June 2007 [ABSTRACT FROM AUTHOR]

Three different methods of setting the hadronic energy scale of a longitudinally segmented calorimeter system are compared with each other. The merits of these methods have been studied with testbeam data from the CDF Plug Upgrade Calorimeter. It turns out that one of the (commonly used) calibration methods introduces a number of undesirable side effects, such as an increased hadronic signal nonlinearity and trigger biases resulting from the fact that the reconstructed energy of hadrons depends on the starting point of their showers. These problems can be avoided when a different calibration method is used. The results of this study are applied to determine the e/h values of the calorimeter and its segments. [Copyright &y& Elsevier]

The electron/hadron separation in the calorimetry can be improved if we measure the electromagnetic shower development at an early stage. The incident positions of electrons and photons can be precisely measured with a position sensitive detector placed near the electromagnetic shower maximum. We constructed a set of prototype preshower and shower-maximum detectors to be attached in front of a main calorimeter. Performance of the detectors was studied in combination with a lead/plastic-scintillator calorimeter module using high energy beams up to 100 GeV at a test beam facility at Fermi National Accelerator Laboratory. [Copyright &y& Elsevier]

The CDF Plug Upgrade calorimeter, which fully exploits the tile–fiber technique, was tested at the Fermilab meson beamline. The calorimeter was exposed to positron, positively charged pion and positive muon beams with energies in the range of 5–230 GeV. The energy resolution of the electromagnetic calorimeter to the positron beam is consistent with the design value of 16%/√ of E⊕1%, where E is the energy in units of GeV and ⊕ represents sum in quadrature. The non-linearity for positrons is studied in an energy range of 11–181 GeV. It is important to incorporate the response of the preshower detector, the first layer of the electromagnetic calorimeter which is readout separately, into that of the calorimeter to reduce the non-linearity to 1% or less. The energy scale is about 1.46 pC/GeV with HAMAMATSU R4125 operated typically at a gain of 2.5×104. The response non-uniformity over the surface of a tower of the electromagnetic calorimeter is found to be about 2% with 57 GeV positrons. Studies of several detailed detector characteristics are also presented. [Copyright &y& Elsevier]

A primary hepatic carcinoid tumor arising in a 49-year-old woman is reported. The patient was admitted with multiple hepatic tumors and treated by a left lobectomy and cholecystectomy. Cut sections of the specimen revealed a solid and necrotic mass, measuring 10 x 12 x 13 cm, with multiple small satellite nodules. Histologically, the tumor cells had small oval-shaped nuclei and presented with a trabecular arrangement and rosette-like formation. Both Grimelius and Fontana-Mason stainings were positive. The tumor cells were positive for chromogranin A and negative for other antigens. Ultrastructural studies of the tumor cells revealed duct-like formation with microvilli and a cluster of dense small immature neurosecretory granules in the cytoplasm. These findings were consistent with those of carcinoid tumors. Postoperatively, the patient was treated with repeated transcatheter arterial chemoembolization for any remnant tumors. However, she died of the disease 5 years after the initial surgery. The autopsy findings suggested the primary site to be the liver. [ABSTRACT FROM AUTHOR]

CLEOPATRA study demonstrated the efficacy and safety of pertuzumab (P) + trastuzumab (T) + docetaxel (D) but efficacy results of Japanese subgroup weren't consistent with the whole study results. A phase IV, multicenter, prospective, COMACHI study was conducted in Japan to re-confirm the efficacy and safety of P+T+D demonstrated in the CLEOPATRA study. Patients (pts) with HER2-positive breast cancer who were diagnosed as Stage IV or recurred more than a year after (neo)adjuvant taxane chemotherapy completion were enrolled. Pts were administered study drugs intravenously every 3 weeks. Discontinuation of D was allowed after cycle 6. After discontinuation of D, pts were given maintenance by T+P, however not allowed to receive hormonal therapy for HR positive pts. We defined PFS as the primary endpoint. To demonstrate a median PFS of 12.4 months (mos) or more, which was observed in the placebo arm in the CLEOPATRA study. From November 2013 to September 2015, 132 pts were enrolled and all pts were treated with T+P at least once. The median age was 56.5 years old and 102 pts (77.3%) had not received prior HER2 therapy. Median cycles of T and P were both 24.0 (range 2.0-71.0) and that of D was 6.0 (range 0.0-65.0). Pts characteristics and subgroup analysis results are shown in the Table below. Table 353P Table Name Level Patients Events Time to event [n (%)] [n (%)] [Median (95% CI)] All n/a 132 (100.0%) 66 (50.0%) 22.8 (16.9, 34.8) Prior (neo) adjuvant therapy(Excluding hormone therapy) YES 38 (28.8%) 18 (47.4%) 27.7 (12.4, NE) NO 94 (71.2%) 48 (51.1%) 20.8 (16.9, 38.8) Age < 65 96 (72.7%) 49 (51.0%) 22.8 (16.5, NE) >- 65 36 (27.3%) 17 (47.2%) 33.1 (18.7, NE) Disease Type at Screening VISCERAL DISEASE 81 (61.4%) 49 (60.5%) 18.4 (13.8, 33.7) NON-VISCERAL DISEASE 51 (38.6%) 17 (33.3%) NE (20.7, NE) ER/PgR Status POSITIVE 72 (54.5%) 39 (54.2%) 18.9 (14.7, 33.1) NEGATIVE 60 (45.5%) 27 (45.0%) 33.7 (20.6, NE) HER2 Status IHC/ISH IHC < = 2+ and ISH POSITIVE 21 (15.9%) 13 (61.9%) 16.5 (10.4, 34.8) IHC 3+ 111 (84.1%) 53 (47.7%) 22.9 (18.9, NE) Stage < STAGE IV 61 (46.2%) 24 (39.3%) 28.4 (22.8, NE) STAGE IV 71 (53.8%) 42 (59.2%) 18.9 (14.3, 33.7) Median PFS was 22.8 mos [95% CI, 16.9-34.8], and thereby a median PFS of 12.4 mos or more was confirmed. The incidence of typical Grade 3/4 adverse events were febrile neutropenia (31.1%), neutropenia (24.2%), leukopenia (10.6%), and diarrhea (4.5%), and these findings are consistent with the CLEOPATRA study except for febrile neutropenia. Febrile neutropenia lead to only one case of treatment discontinuation and it was manageable. The efficacy and safety of P+T+D in Japanese pts were consistent with those of the CLEOPATRA study and we confirmed this treatment as a standard care at 1st line therapy for HER2-positive metastatic breast cancer. Chugai Pharmaceutical Co., Ltd. Chugai Pharmaceutical Co., Ltd. N. Masuda: Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eli-Lilly; Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Kyowa-Kirin; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Daiichi Sankyo; Officer / Board of Directors: Japan Breast Cancer Research Group Association. S. Ohtani: Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony: AstraZeneca. S. Nagai: Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli-Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd. Y. Komoike: Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Eli-Lilly; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Taiho; Speaker Bureau / Expert testimony, the publisher, for writing atricle: Nikkei Business Publications, Inc. Y. Ito: Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Speaker Bureau / Expert testimony, Research grant / Funding (self): Taiho; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eli-Lilly; Speaker Bureau / Expert testimony, Research grant / Funding (self): Eisai; Research grant / Funding (institution): Covance; Research grant / Funding (institution): IQVIA; Research grant / Funding (institution): MSD; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): A2healthcare; Research grant / Funding (institution): Parexel; Research grant / Funding (institution): Kyowa-Kirin. M. Ikeda: Advisory / Consultancy, Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Daiichi Sankyo; Speaker Bureau / Expert testimony: Asahi Kasei Pharma Corporation; Speaker Bureau / Expert testimony: Kyowa-Kirin; Speaker Bureau / Expert testimony: Ono; Speaker Bureau / Expert testimony: Mundipharma; Speaker Bureau / Expert testimony: Taiho; Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony: Nippon Kayaku; Research grant / Funding (institution): Hisamitsu; Officer / Board of Directors, engaged in the project of medical practice guidline: Japanese Breast cancer society; Officer / Board of Directors, the leader of clinical trial comittee: Setouchi Breast Project Comprehensive Support Organization. K. Ishida: Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony: Nippon Kayaku. T. Nakayama: Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Eli-Lilly; Speaker Bureau / Expert testimony: Novartis. T. Takashima: Speaker Bureau / Expert testimony, Officer / Board of Directors: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony, Officer / Board of Directors: AstraZeneca; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony: Kyowa-Kirin; Speaker Bureau / Expert testimony: Eli-Lilly. T. Asakawa: Full / Part-time employment: Chugai Pharmaceutical Co., Ltd. S. Matsumoto: Full / Part-time employment: Chugai Pharmaceutical Co., Ltd. D. Shimizu: Full / Part-time employment: Chugai Pharmaceutical Co., Ltd. M. Takahashi: Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eisai; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Eli-Lilly; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Kyowa-Kirin; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Taiho; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Daiichi Sankyo; Speaker Bureau / Expert testimony: Allergan; Speaker Bureau / Expert testimony, Research grant / Funding (institution): FUJIFILM Toyama Chemical; Speaker Bureau / Expert testimony: Nihon Medi-Physics; Honoraria (self), for wrtitin article: The Asahi Shimbun Company. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]