帰納と合理性

はじめに　Ⅰ 因果的推論の基礎　§1 印象と観念　§2 七つの哲学的関係　§3 I必然的結合」の観念　Ⅱ合理性の破産　§4 信念の本性　§5 懐疑主義的結論に対するヒュームの態度　§6 非合理的信念の奔流　Ⅲ帰納と科学　§7 生得的期待　§8 科学の目的　§9 テスト言明の理論依存性

Tofacitinib as induction and maintenance therapy for ulcerative colitis

Background: Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial. We further evaluated the efficacy of tofacitinib as induction and maintenance therapy. METHODS: We conducted three phase 3, randomized, double-blind, placebo-controlled trials of tofacitinib therapy in adults with ulcerative colitis. In the OCTAVE Induction 1 and 2 trials, 598 and 541 patients, respectively, who had moderately to severely active ulcerative colitis despite previous conventional therapy or therapy with a tumor necrosis factor antagonist were randomly assigned to receive induction therapy with tofacitinib (10 mg twice daily) or placebo for 8 weeks. The primary end point was remission at 8 weeks. In the OCTAVE Sustain trial, 593 patients who had a clinical response to induction therapy were randomly assigned to receive maintenance therapy with tofacitinib (either 5 mg or 10 mg twice daily) or placebo for 52 weeks. The primary end point was remission at 52 weeks. RESULTS: In the OCTAVE Induction 1 trial, remission at 8 weeks occurred in 18.5% of the patients in the tofacitinib group versus 8.2% in the placebo group (P=0.007); in the OCTAVE Induction 2 trial, remission occurred in 16.6% versus 3.6% (P<0.001). In the OCTAVE Sustain trial, remission at 52 weeks occurred in 34.3% of the patients in the 5-mg tofacitinib group and 40.6% in the 10-mg tofacitinib group versus 11.1% in the placebo group (P<0.001 for both comparisons with placebo). In the OCTAVE Induction 1 and 2 trials, the rates of overall infection and serious infection were higher with tofacitinib than with placebo. In the OCTAVE Sustain trial, the rate of serious infection was similar across the three treatment groups, and the rates of overall infection and herpes zoster infection were higher with tofacitinib than with placebo. Across all three trials, adjudicated nonmelanoma skin cancer occurred in five patients who received tofacitinib and in one who received placebo, and adjudicated cardiovascular events occurred in five who received tofacitinib and in none who received placebo; as compared with placebo, tofacitinib was associated with increased lipid levels. CONCLUSIONS: In patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo. (Funded by Pfizer; OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain ClinicalTrials.gov numbers, NCT01465763 , NCT01458951 , and NCT01458574 , respectively.

Circulating CD4‐positive lymphocyte levels as predictor of response to induction chemotherapy in patients with advanced laryngeal cancer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102107/1/hed23263.pd

First-line ovulation induction for polycystic ovary syndrome : an individual participant data meta-analysis

Acknowledgements We would like to thank Mr M. Draper from Barr Smith Library, University of Adelaide, for his assistance in developing the search strategies and Dr M. H. Zafarmand from University of Amsterdam for assisting with the translation. We would like to acknowledge all the investigators and participants of the primary trials. The investigators of individual trials are listed in Supplementary Table SIV. We would like to acknowledge the assistance of NICHD, the Reproductive Medicine Network (RMN) and the Protocol Subcommittee, in making the database for PPCOS I and II available. +The authors of the Reproductive Medicine Network are R.S.L., R.G. Brzyski, M.P. Diamond, C. Coutifaris, W.D. Schlaff, P. Casson, G.M. Christman, H. Huang, Q. Yan, R. Alvero, D.J. Haisenleder, K.T. Barnhart, G.W. Bates, R. Usadi, S. Lucidi, V. Baker, J.C. Trussell, S.A. Krawetz, P. Snyder, D. Ohl, N. Santoro, H.X. Barnhart, B.R. Carr, S.A. Carson, M.P. Steinkampf, P.G. McGovern, N.A. Cataldo, G.G. Gosman, J.E. Nestler, L.C. Giudice, P.C. Leppert, E.R. Myers, E. Eisenberg and H. Zhang. The details of their affiliations and NIH Grants are listed in Supplementary Table SV. Funding An Australian government research training programme scholarship (to R.W.); Australian National Health and Medical Research Council-funded Centre for Research Excellence in Polycystic Ovary Syndrome (APP1078444). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.Peer reviewedPostprin

Supracricoid partial laryngectomy in the management of t3 laryngeal cancer

Objective. To evaluate the oncologic results only in T3 glottic and supraglottic cancers regarding supracricoid partial laryngectomy (SCPL) not requiring total laryngectomy and to assess functional results by self-evaluation by the patient. Study Design. Case series with medical record review. Setting. Single tertiary care center. Subjects and Methods. Thirty-two patients with laryngeal squamous cell carcinoma, previously untreated, who underwent SCPL with cricohyoidopexy or cricohyoidoepiglottopexy were reviewed. Results. At 1, 3, and 5 years, the disease-free survival rates were 96.9%, 89.4%, and 78.2%; overall survival rates were 96.9%, 93.2%, and 87.3%; local control and locoregional control rates were 100%, 96.2%, and 96.2%; and distant metastasis-free survival rates were 100%, 100%, and 88.2%, respectively. Aspiration pneumonia was the most common complication observed. The 3 laryngeal functions (speech, swallowing, and breathing) were spared in 83.9% of patients. Conclusion. Supracricoid partial laryngectomy for selected glottic and supraglottic T3 tumors has excellent oncologic and functional results

Position of an Active Thiosulfonate Group in New

Synthetic water-soluble phenolic antioxidants are known anti-inflammatory chemicals, some of them were shown to induce components of antioxidative defense enzymes NADPH:quinone oxidoreductase (NQO1) and glutathione-S-transferase (GST) via activation of Nrf2 pathway. Our experimental in vivo models have demonstrated an increase of both gstp1 and nqo1 expression in the liver of mice treated with novel organosulfur phenolic compounds TS-12, TS-13, TS-14. Both expression and activity of GSTP1 was dependent on the distance of active thiosulfonate group in para- position from the benzene ring of the above antioxidants. The increase of nqo1 and gstp1 gene expression was mediated by the antioxidant-binding response element (ARE). Our results revealed the role of Nrf2/ARE-dependent transcription regulation in response to the new phenolic antioxidants and suggested possible strategy to improve antioxidative properties of synthetic phenolic compounds