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Mikito Kawamata,1 Masako Iseki,2 Mamoru Kawakami,3 Shoji Yabuki,4 Takuma Sasaki,5 Mitsuhiro Ishida,5 Atsushi Nishiyori,5 Hideaki Hida,6 Shin-ichi Kikuchi4 1Department of Anesthesiology and Resuscitology, Shinshu University School of Medicine, Matsumoto, Japan; 2Department of Anesthesiology and Pain Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan; 3Spine Care Center, Wakayama Medical University Kihoku Hospital, Wakayama, Japan; 4Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan; 5Clinical Development Department, Shionogi & Co., Ltd., Osaka, Japan; 6Biostatistics Center, Shionogi & Co., Ltd., Osaka, JapanCorrespondence: Takuma SasakiClinical Development Department, Shionogi & Co., Ltd., 12F, Hankyu Terminal Bld., 1-4, Shibata 1-chome, Kita-ku, Osaka 530-0012, JapanTel +81-6-6485-5090Fax +81-6-6375-5780Email Takuma.sasaki@shionogi.co.jpPurpose: To assess the efficacy and safety of S-8117, an oral, controlled-release formulation of oxycodone hydrochloride, in Japanese patients with chronic non-cancer pain (CNCP).Patients and methods: In this multicenter, non-randomized, open-label, 2-part (part 1, dose-titration followed by maintenance period; part 2, long-term administration period) study at 38 centers in Japan (2013–2015), adult patients with CNCP for ≥12 weeks were administered S-8117. The primary endpoint was proportion of patients with successful maintenance of pain control in part 1 and long-term safety in part 2. Secondary endpoints included time to inadequate analgesia, rate of transition to the maintenance period, and discontinuation due to inadequate analgesia/adverse events (AEs), Brief Pain Inventory (BPI) pain severity, BPI pain interference, 36-item Short Form Health Survey (SF-36) score, and Western Ontario and McMaster Universities (WOMAC) index, Subjective Opioid Withdrawal Scale (SOWS), Clinical Opioid Withdrawal Scale (COWS), Dependency-2-A (D-2-A), and Dependency-2-B (D-2-B) questionnaires.Results: Of 130 patients (mean age, 63.6 years; women, 62.3%) in the dose-titration period, 95 entered the maintenance period; 60 of 83 who entered the long-term administration period completed it. The proportion of patients (95% confidence interval) with successful maintenance of pain control, transition to maintenance period, and discontinuation due to inadequate analgesia/AEs was 78.9% (69.4–86.6), 73.1% (64.6–80.5), and 21.1% (13.4–30.6), respectively. Time to inadequate analgesia could not be estimated. Changes from baseline in BPI, SF-36, and WOMAC index scores suggested improvements in pain relief and quality of life. Based on the SOWS, COWS, D-2-A and D-2-B questionnaires, no patient developed clinically relevant withdrawal syndrome or was ascertained to have developed drug dependence. Overall, the incidence of treatment-emergent AEs (TEAEs) was 93.8%; most common TEAEs were constipation (49.2%), nausea (42.3%), nasopharyngitis (34.6%), and somnolence (32.3%).Conclusion: These results demonstrate the efficacy and safety of S-8117 in Japanese patients with CNCP.Keywords: analgesics, chronic pain, Japan, opioids

Mikito Kawamata,1 Masako Iseki,2 Mamoru Kawakami,3 Shoji Yabuki,4 Takuma Sasaki,5 Mitsuhiro Ishida,5 Atsushi Nishiyori,5 Hideaki Hida,6 Shin-ichi Kikuchi4 1Department of Anesthesiology and Resuscitology, Shinshu University School of Medicine, Matsumoto, Japan; 2Department of Anesthesiology and Pain Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan; 3Spine Care Center, Wakayama Medical University Kihoku Hospital, Wakayama, Japan; 4Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan; 5Clinical Development Department, Shionogi & Co. Ltd., Osaka, Japan; 6Biostatistics Center, Shionogi & Co. Ltd., Osaka, Japan Background: Oxycodone is one of the options for the management of CLBP in patients with an inadequate response to other analgesics. However, oxycodone is not yet approved for noncancer pain in Japan. Here, we assessed the efficacy and long-term safety of S-8117, a controlled-release oxycodone formulation, for the management of Japanese CLBP patients. Patients and methods: An initial enriched enrollment randomized withdrawal, double-blind, placebo-controlled, 5-week phase III trial was conducted across 54 centers in Japan to assess the efficacy of S-8117 vs placebo in moderate-to-severe CLBP patients. Subsequently, a 52-week, open-label, single-arm study was conducted across 53 centers in Japan to evaluate the long-term safety of S-8117. The primary endpoint was the time to inadequate analgesic response during 35 days of the double-blind period. Secondary endpoints were the percentages of patients with inadequate analgesic response, discontinuation rate due to inadequate analgesic effects or AEs, and changes in scores of BPI severity, BPI pain interference, SF-36, and Roland-Morris Disability Questionnaire. Safety was assessed as the incidence of AEs and ADRs. Results: Of the 189 patients enrolled in the double-blind study, 130 patients who completed the initial titration period were randomized 1:1 to receive either S-8117 (n=62) or placebo (n=68). Baseline characteristics were comparable across the study groups. The time to inadequate analgesic response was significantly longer in patients treated with S-8117 than placebo (P=0.0095). Secondary endpoints corroborated the efficacy of S-8117 vs placebo. Overall, 478 AEs were reported in 73/75 patients in the long-term study. The most frequent ADRs were somnolence, constipation, and nausea. No case of drug dependence was reported in the long-term study. Conclusion: Short-term efficacy vs placebo and long-term safety of S-8117 were demonstrated for the management of Japanese patients with moderate-to-severe CLBP. Keywords: chronic low back pain, opioids, oxycodone, RCT

Let p ≥ 5 be a prime. If an irreducible component of the spectrum of the 'big' ordinary Hecke algebra does not have complex multiplication, under mild assumptions, we prove that the image of its Galois representation contains, up to finite error, a principal congruence subgroup Γ(L) of SL2(Zp[[T]]) for a principal ideal (L) = 0 of Zp[[T]] for the canonical 'weight' variable t=1+T. If L ∞ Λ×, the power series L is proven to be a factor of the Kubota-Leopoldt p-adic L-function or of the square of the anticyclotomic Katz p-adic L-function or a power of (tpm-1). This journal is

We prove a transcendence result of Hecke operator T.(l) over the ring generated by diamond operators over ℚ in a non-CM component of the cyclotomic ordinary big p-adic Hecke algebra, and we discuss its conjectural implication of a modulo-p version to the vanishing of the cyclotomic μ-invariant. © 2014.

Let p≥5 be a prime. If an irreducible component of the spectrum of the 'big' ordinary Hecke algebra does not have complex multiplication, under mild assumptions, we prove that the image of its mod p Galois representation contains an open subgroup of [InlineEquation not available: see fulltext.] for the canonical "weight" variable T. This fact appears to be deep, as it is almost equivalent to the vanishing of the μ-invariant of the Kubota-Leopoldt p-adic L-function and the anticyclotomic Katz p-adic L-function. Another key ingredient of the proof is the anticyclotomic main conjecture proven by Rubin/Mazur-Tilouine. © 2012 Springer-Verlag Berlin Heidelberg.

For a quaternion algebra B over a totally real field F unramified at every finite place and ramified most at infinite places of F, we prove that the space of Z[1/E]$-integral Hilbert modular forms of weight 2 and of level 1 is spanned over Z[1/E] by the theta series of the norm form of B. Here E is an explicit constant given by the product of 6, the discriminant of F and the value at -1 of Hecke L-functions of conductor 1.

Describes novel rapid thermal annealing for gallium arsenide wafers under vacuum conditions using a three-zone lamp power control method. Experimental details; Effect of three-zone lamp-power control on temperature uniformity; Slip-line generation and wafer deformation; Result of the study.