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BackgroundDifficult-to-treat rheumatoid arthritis (D2T RA) is defined as RA in which disease activity is uncontrolled despite the use of two or more biologics or Janus kinase inhibitors (JAKi) with different mechanisms of action (MOA).ObjectivesTo explore the optimal treatment strategy for D2T RA, we evaluated the drug retention, efficacy, and reasons for discontinuation of biologics or JAKi used for patients with D2T RA in a longitudinal multicenter cohort.MethodsRA patients with clinical disease activity index (CDAI) >10 despite the use of at least two biologics or JAKi with different MOA and further treated with biologics or JAKi were included. The drug retention rates of biologics (TNFi, IL-6Ri, and CTLA4-Ig) or JAKi were estimated at 12 months using the Kaplan-Meier method and adjusted for potential confounders (age, sex, disease duration, concomitant MTX and PSL use, and the number of switched biologics or JAKi) using Cox proportional hazards models.ResultsA total of 251 treatment courses (TCs) from 167 patients were included (TNFi: 97 TCs, IL-6Ri: 67 TCs, CTLA4-Ig: 27 TCs, JAKi: 60 TCs). Baseline characteristics showed no difference in age, sex, disease duration, ACPA positivity, CDAI, and concomitant MTX and PSL use between the four groups. Drug retention excluding non-toxic reasons and remission was significantly higher in patients treated with JAKi or IL-6Ri than in patients treated with TNFi or CTLA4-Ig (P=0.00172). Multivariate analysis using Cox proportional hazards models demonstrated that discontinuation of the drug was associated with the use of TNFi or CTLA4-Ig (HR: 3.29, 95%CI: 1.15-9.42, P=0.027) and concomitant PSL use (HR: 1.14, 95%CI: 1.04-1.26, P=0.0084). In terms of disease activity evaluated with CDAI, no difference was observed between the four groups at 3 months (P=0.90), at 6 months (P=0.77), and at 12 months (P=0.75).ConclusionIn patients with D2T RA, JAKi or IL-6Ri may have treatment advantages compared with TNFi or CTLA4-Ig.References[1] EULAR definition of difficult-to-treat rheumatoid arthritis.Nagy G, Roodenrijs NMT, Welsing PM, Kedves M, Hamar A, van der Goes MC, Kent A, Bakkers M, Blaas E, Senolt L, Szekanecz Z, Choy E, Dougados M, Jacobs JW, Geenen R, Bijlsma HW, Zink A, Aletaha D, Schoneveld L, van Riel P, Gutermann L, Prior Y, Nikiphorou E, Ferraccioli G, Schett G, Hyrich KL, Mueller-Ladner U, Buch MH, McInnes IB, van der Heijde D, van Laar JM.Ann Rheum Dis. 2021 Jan;80(1):31-35.[2] Prevalence and predictive factors of difficult-to-treat rheumatoid arthritis: the KURAMA cohort.Watanabe R, Hashimoto M, Murata K, Murakami K, Tanaka M, Ohmura K, Ito H, Matsuda S.Immunol Med. 2021 May 25:1-10.Disclosure of InterestsRyu Watanabe Speakers bureau: Eli Lilly, Mitsubishi Tanabe, Pfizer, Sanofi, AbbVie, Asahi Kasei, Eisai, Bristol-Myers Squibb, UCB Japan, Chugai, Janssen, Astellas, Nippon Shinyaku, Daiichi Sankyo, Gilead Sciences Japan, and Boehringer ingelheim., Tadashi Okano Speakers bureau: Asahi Kasei, Astellas, Abbvie, Amgen, Ayumi, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead Sciences, Janssen, Kyowa Kirin, Mitsubishi Tanabe, Novartis, Ono, Pfizer, Sanofi, Takeda, UCB, Grant/research support from: Asahi Kasei, Abbvie, Chugai, Eisai, Mitsubishi Tanabe, Shinsuke Yamada: None declared, Wataru Yamamoto: None declared, Koichi Murata Speakers bureau: Eisai Co., Ltd., Chugai Pharmaceutical Co., Ltd.; Asahi Kasei Pharma Corp.; and Mitsubishi Tanabe Pharma Co., and Daiichi Sankyo Co. Ltd., Kosaku Murakami: None declared, Kosuke Ebina Speakers bureau: AbbVie, Amgen, Asahi-Kasei, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Janssen, Mitsubishi-Tanabe, Ono Pharmaceutical, Pfizer, Sanofi, and UCB Japan., Grant/research support from: AbbVie, Amgen, Asahi-Kasei, Astellas, Chugai, Eisai, Mitsubishi-Tanabe, Ono Pharmaceutical, Teijin Pharma, and UCB Japan, Yuichi Maeda Speakers bureau: Eli Lilly Japan K.K., Chugai Pharmaceutical Co. Ltd., Pfizer Inc., Bristol Myers Squibb, and Mitsubishi Tanabe Pharma Corporation., Sadao Jinno Speakers bureau: AbbVie G.K., Asahi Kasei Pharma., Bristol-Myers Squibb., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., and Mitsubishi Tanabe Pharma, and Ono Pharmaceutical Co, Iku Shirasugi: None declared, Yonsu Son: None declared, Hideki Amuro Speakers bureau: Chugai Pharmaceutical Co.,Ltd, Masaki Katayama: None declared, Ryota Hara: None declared, Kenichiro Hata Speakers bureau: AbbVie, Asahi-Kasei, Chugai, Janssen, Mitsubishi-Tanabe, Eisai, Ayaka Yoshikawa: None declared, Motomu Hashimoto Grant/research support from: Abbvie, Asahi-Kasei, Brystol-Meyers, Eisai, Eli Lilly, Novartis Pharma.

Objectives To describe the results of orthogonal plating (OP) as a treatment for fractures of the radius and ulna in toy-breed dogs. Materials and methods The medical records (June 2011 to April 2019) of toy-breeds in which the OP technique using non-locking cuttable plates was employed to treat radial and ulnar fractures were reviewed. The inclusion criteria included a bodyweight of 3.5 kg or less, fracture of the diaphysis of the radius and ulna of one or both forelimbs, and the availability of follow-up radiographs. Revision surgeries were also included. Results Fifteen limbs that underwent initial fracture repair and five that underwent revision surgery met the inclusion criteria. The radial and ulnar fractures healed in 19 limbs at the final follow-up. Synostosis of the radius and ulna at the fracture sites was observed in one limb. Re-fracture after cranial plate removal was observed in one case. All dogs exhibited successful return of normal limb function at the final clinical and radiographic follow-up (mean, 104.7 ± 67.1 days; median, 79.5 days; range: 35 to 248 days). Long-term follow-up data obtained via telephone interviews to owners or referring veterinarians were available for 15 cases and confirmed maintenance of normal limb function in all dogs (mean, 32.5 ± 17.6 months; median, 26 months; range: 11 to 69 months). Clinical significance OP allowed the successful open reduction of radial and ulnar fractures, facilitating bone union in both the radius and ulna and a return to normal limb function in a series of toy-breed dogs.

Biological disease-modifying anti-rheumatic drugs (bDMARDs) against pathogenic proinflammatory cytokines and lymphocytes, such as tumour necrosis factor-α (TNF-α), interleukin-6, T cells and B cell...

In this chapter, various vanadium-oxide clusters are exhibited and their spontaneous formation in solution is rationalized. Unlike organic chemistry that is governed by the formation of covalent bonds, inorganic-oxide molecules are dynamic species due to their flexible ionic bonds and have an exquisite beauty showing a spectrum of beautiful colours arising from various coordination modes and valence states. In a catalytic reaction using a vanadate source, vanadium-oxide clusters are often formed and transformed – it is also easy to restore the structure back to the original form. The relative easiness of the transformation in a different structure of blocks, tubes, bowls, cages, spheres and rings is key to understanding each catalytic process. The analogy between the graphite structure and the V2O5 stacked-2D-sheet structure explains the formation of tubes and spheres and is reminiscent of the discovery of nano-tubes and fullerenes in carbon chemistry. Vanadium chemistry enjoys an easiness of modification and incorporation of a guest molecule that it can feasibly control compared to the stubborn fullerene host–guest complex.

Background:Several study suggested body mass index(BMI) may influence development of rheumatoid arthritis(RA). There are conflicting reports concerning the impact of high BMI on development of RA, but several reports of obese on drug resistance and functional impairment. The relationship of genetic polymorphism on obesity is unclear in RA.Objectives:To examine the relationship among BMI, genetic polymorphism of obesity, disease activity of RA, laboratory parameters, and therapeutic agent of RA.Methods:We have carried out a retrospective observational study by systematically analyzing medical records of total 289 patients diagnosed with RA in Shinko Hospital between March 2016 and December 2019. We also conducted genotyping single nucleotide polymorphisms (SNPs) including FTO (rs1558902 and rs9939609), UCP1 (rs1800592), ADR2(rs1042713) and ADR3(rs4994) after informed consent. Obesity was defined as BMI over than 25 and patients were divided between obese (“Ob”) and non-obese (“non-Ob”). These SNPs, DAS28CRP, laboratory parameters, methotrexate dose, use of biological DMARDs were compared between Ob and non-Ob patients.Results:Of these 289 patients, 82.7% was female, mean age was 61.9 years and BMI was 22.4. Univariate logistic regression showed differences (pConclusion:Obesity in patients with RA had significant positive correlation with γGTP, and negative correlation with HDL, UCP gene mutation and MTX dose.Disclosure of Interests:None declared

Background:Tacrolimus (TAC), an immunosuppressant, can be used in second-line maintenance therapy for interstitial lung disease (ILD) in patients with dermatomyositis (DM) [1]. Although some studies reported the clinical efficacy of initial high-trough levels of TAC in combination with GC and IVCY in induction therapy for severe DM-ILD [2], there have been no useful clinical tools for deciding suitable initial dose of TAC. Genotype of polymorphisms in cytochrome P450 (CYP) 3A5 enzyme was reported to play an important role in pharmacokinetics of TAC [3], and we made a formula for deciding initial dose of TAC according to CYP3A5 genotypes in our previous study.Objectives:In our previous study (retrospective study), we set the target trough according to the severity for nine DM-ILD patients, six of whom were CYP3A5 *3/*3 and investigated the dose of TAC that could attain the trough using their CYP3A5 genootyping. Using these results, we developed a formula for deciding initial daily dose of TAC (target trough*weight / [(151.1, if CYP3A5 *3/*3) or (86.5, if CYP3A5 *1 allele)]). In this study, we prospectively examined the usefulness and accuracy of this formula.Methods:We introduced TAC for new six DM-ILD patients who visited our hospital between November 2019 and May 2020 (prospective study). The starting dose of TAC was decided by using the formula. We assessed the association between predicted and observed trough concentration of TAC at first measurement date (from day 2 to day4), using linear regression analysis. We also assessed the days for attaining the target trough concentration between the patients using the formula (prospective group) and six patients with CYP3A5 *3/*3 (retrospective group).Results:CYP3A5 genotype of all six DM-ILD patients were *3/*3 and underwent the TAC treatment by using the formula. The predicted and observed trough concentration of first measurement date were significantly correlated in the patients (r 2= 0.897, p=0.0041) (Fig.1). Compared with our retrospective study, target trough was more quickly attained in patients of the prospective study (Fig.2).Conclusion:The formula which we made for attainment target trough concentration based on CYP3A5 genotype was useful for deciding the starting dose of TAC. We also showed that we could attain the target trough concentration at early stage of initial treatment by using the formula.References:[1]Oddis CV and Aggarwal R. Nat Rev Rheumatol 2018;14(5):279-89.[2]Suzuka T et al. Int J Rheum dis 2019;22: 303-13.[3]Y. Muraki et al. Exp Ther Med 2018;15:532-38.Figure 1.Correlation of predicted and observed tacrolimus trough concentration at first measurement in the prospective studyFigure 2.Days to attain the target trough concentration of tacrolimus in the prospective group and the retrospective groupDisclosure of Interests:None declared

Background:MTX is transported into cells and retained long after polyglutamation. MTXPG level can predict response and possibly adverse effects of MTX. We reported erythrocyte MTXPG concentrations efficiently discriminated patients with and without hepatotoxicity1. We also developed genetic and clinical prediction models for efficacy and hepatotoxicity of MTX2. In the present study, we firstly investigated the effects of clinical and secondly genetic variables on the concentration of total MTXPG and determined oral maximum MTX dose without hepatotoxicity using these variables.Objectives:To develop a prediction model for maximum MTX dose without hepatotoxicity.Methods:Concentrations of erythrocyte MTX-PG (PG1 to PG4) were detected by LC-MS/MS and calculated total MTXPG as sum of them. MTX-PGn levels were measured in 265 RA patients including 40 patients with elevated AST or ALT (≥ 60 U/L; 1.5 times of upper limits) and the 6 SNPs of 6 gens related to MTXPG metabolism were identified by RT-PCR.Results:Total concentrations of MTXPG were 141.3 ± 86.5 and 87.6 ± 47.8 nmol/L (mean±SD) in 40 RA patients with hepatotoxicity and 225 patients without, respectively (pT) was developed (Figure). When MTXPG concentration of 100 nmol/L was applied to the model, maximum MTX dose without hepatotoxicity was calculated for each patient asMTX dose (mg) = {100 (MTXPG) – 96 + 1.7*BMI + 28*RBC - 120*creatinine - 19.3*GGH(C/T)} / 7.7. Real dose of oral MTX exceeded the calculated dose in 23 of 40 patients (57.5%) with hepatotoxicity, whereas it exceeded in 95 of 223 patients (42.6%) without hepatotoxicity (OR 1.82, p=0.081).Conclusion:Maximum MTX dose without hepatotoxicity was speculated by several clinical and genetic markers without measurement of erythrocyte MTX-PG concentrations.References:[1]Takahashi M, et al: Clinical Pathology (Rinsho Byori), 67:433-442, 2019.[2]Onishi A, et al: The Pharmacogenomics J, doi.org/10.1038/s41397-019-0134-9, 2019Disclosure of Interests:Shunichi Kumagai Grant/research support from: Astellas, Chugai, Mitsubishi Tanabe Co.Ltds, Consultant of: Sysmex Co.Ltd, Speakers bureau: many companies, Soshi Takahashi: None declared, Miho Takahashi: None declared, Toshiharu Saito: None declared, Katsuyuki Yoshida: None declared, Motoko Katayama: None declared, Saki Mukohara: None declared, Norihiko Amano: None declared, Akira Onishi Speakers bureau: AO received a speaker fee from Chugai, Ono Pharmaceutical, Eli Lilly, Mitsubishi-Tanabe, Asahi-Kasei, and Takeda, Masakazu Shinohara: None declared, Saori Hatachi: None declared

Oxygen is used for medical treatment and general anesthesia. However, high concentrations of oxygen can have toxic effects on cells. In veterinary medicine, 100% oxygen is usually used during general anesthesia and it can be toxic to animals. However, there is little concern about its harmful effects in humans. The objective of this study was to demonstrate that using a high con- centration of oxygen increases the partial pressure of oxygen in arterial blood (PaO2) more so than a lower concentration, by comparing PaO2 at three different oxygen concentrations (100%, 60%, and 40%) in six dogs under general anesthesia for 3 hours. The mean PaO2 and standard error values at the 100%, 60%, and 40% oxygen concentrations were 535.8 ± 24.01, 374 ± 17.19, and 239 ± 8.78 mmHg, respectively (p⟨0.05). These results show that 100% and 60% oxygen concentrations could increase oxidative stress. Further studies are needed to examine the oxygen concentration that causes toxicity.

Background:Though several studies showed the efficacy of tacrolimus (TAC) in patients with rheumatoid arthritis (RA) in a dose-depending manner [1], the relationship between efficacy and concentration of TAC remained unclear. Genetic polymorphisms of cytochrome P450 (CYP) 3A5 were reported not only to play an important role in pharmacokinetics of TAC but also to have an influence on clinical outcomes in patients of rheumatic diseases. Several reports showed that the blood concentration of TAC in patients with a CYP3A5 *1 allele (EX, expressor) was lower than that of patients with a CYP3A5 *3/*3 (NEX, non-expressor) [2].Objectives:To assess the relationship between efficacy and concentration of TAC in patients with RA, and to examine the usefulness of CYP3A5 genotype screening to detect outpatients suitable for TAC treatment.Methods:We examined the relationship between disease activity score (DAS) 28-CRP and concentration of TAC in patients with RA. TAC was taken after the evening meal and blood samples were taken 12±4h after TAC administration. Next we investigated the relationship between genotype frequencies of CYP3A5 and concentration of TAC in patients with rheumatic disease without having renal dysfunction (eGFRResults:The concentration of TAC tended to be negatively correlated with the disease activity of RA. The C/D value in the NEX group (n=16) was 124.7±62.1, which was significantly higher than that in the EX group (n=23; 67.7±29.8;PConclusion:TAC showed efficacy in patients with RA in a concentration-dependent manner. EX patients may be impossible to achieve enough concentration of TAC even though using TAC of 3mg/day, approved dose for patients with RA in Japan, and NEX patients could make rapid attainment of enough concentrations of TAC in early stage of treatment, suggesting that we should consider induction of TAC only in NEX outpatients. Furthermore, drugs only slightly affected concentration of TAC in this study, suggesting that we can use TAC without any special attention to concomitant drugs.References:[1]Furst DE et al. Arthritis Rheum 2002;46:2020-28.[2]Y. Muraki et al. Exp Ther Med 2018;15:532-38.Acknowledgments:noneDisclosure of Interests:Soshi Takahashi: None declared, Shinji Horibata: None declared, Saori Hatachi: None declared, Miho Takahashi: None declared, Motoko Katayama: None declared, Saki Mukohara: None declared, Norihiko Amano: None declared, Katsuyuki Yoshida: None declared, Kennosuke Yorifuji: None declared, Shunichi Kumagai Grant/research support from: Astellas, Chugai, Mitsubishi Tanabe Co.Ltds, Consultant of: Sysmex Co.Ltd, Speakers bureau: many companies

Background:Tacrolimus (TAC), an immunosuppressant, can be used in second-line maintenance therapy of interstitial lung disease (ILD) in patients with dermatomyositis (DM) [1]. In Japan, TAC is approved for DM-ILD and often used as induction therapy for severe cases, especially in patients with anti-MDA5-Ab (melanoma differentiation-associated gene 5 antibody) positive, in combination with glucocorticoids (GC) and intravenous cyclophosphamide (IVCY). Some studies reported the clinical efficacy of initial high-trough level TAC for DM-ILD in combination with GC and IVCY [2]. Adjustment to target concentration of TAC in early stage of treatment is important for controlling disease activity. The concentration of TAC depends on genetic polymorphisms in cytochrome P450 (CYP) 3A5 enzyme expression and several reports showed that the bioavailability and concentration of TAC in patients with a CYP3A5 *1 allele (*1) was lower than those with a CYP3A5 *3/*3 (*3/*3) [3].Objectives:To examine the usefulness of CYP3A5 polymorphisms in decision of initial dose to achieve the target concentration of TAC and to evaluate the clinical efficacy in patients of DM-ILD who achieved the enough concentration of TAC in early stage of treatment.Methods:We investigated CYP3A5 polymorphisms and TAC concentration in 9 patients of DM-ILD without renal dysfunction (eGFR>60). TAC was taken after both morning and evening meals and blood samples were taken 12h after TAC administration. The blood concentration of TAC normalized to the corresponding dose per body weight (C/D, ng/ml per mg/kg) was analyzed according to genetic variation in CYP3A5. Based on the retrospective analyzation, we chose proper dose of TAC in initial treatment for an anti-MDA5-Ab positive DM-ILD patient, whose genotype was *3/*3.Results:The C/D value in the *3/*3 group (n=6) was 154.6±25.6, which was significantly higher than that in the *1 group (n=3;79.0±2.8; P =0.028). When the target concentration was set at 5-10 ng/ml, the required dose was (0.0316 to 0.0633) mg/kg in the *1 group and (0.0162 to 0.0324) mg/kg in the *3/*3 group. The *1 group needs more dose than that of the *3/*3 group to achieve the same target trough of TAC, suggesting that the examination of CYP3A5 genotype is useful for deciding initial dose of TAC (Fig.1). We started TAC 6mg/day with setting target concentration at 15-20 ng/ml to a *3/*3 patient of DM-ILD with anti-MDA5-Ab positive, resulting in good clinical course with making rapid attainment of target concentration in early stage of treatment (Fig.2).Conclusion:To examine the CYP3A5 genotype is valuable for deciding the initial dose of TAC, especially in patients who need achievement to target concentration rapidly.References:[1]Oddis CV and Aggarwal R. Nat Rev Rheumatol 2018;14(5):279-89.[2]Suzuka T et al. Int J Rheum dis 2019;22: 303-13.[3]Y. Muraki et al. Exp Ther Med 2018;15:532-38.Acknowledgments:noneDisclosure of Interests:motoko katayama: None declared, Shinji Horibata: None declared, Soshi Takahashi: None declared, Miho Takahashi: None declared, Saki Mukohara: None declared, Norihiko Amano: None declared, Katsuyuki Yoshida: None declared, Saori Hatachi: None declared, Kennosuke Yorifuji: None declared, Shunichi Kumagai Grant/research support from: Astellas, Chugai, Mitsubishi Tanabe Co.Ltds, Consultant of: Sysmex Co.Ltd, Speakers bureau: many companies

Adhesion and bounce of liquid and solid particles upon high-velocity impact with a surface has been investigated using semi-empirical and explicit hydrodynamic simulations. Ammonium nitrate (AN) and sodium chloride (NaCl) were selected as test compounds for the liquid and solid particles, respectively, and tungsten (W) as the target surface. Changes in the shape, temperature, strain, and rebound velocity of these particles upon high-velocity impact are investigated assuming operational conditions (particle diameter, and velocity) of Aerodyne aerosol mass spectrometer (AMS). The simulations show that the AN particles adhere to the W surface, which is consistent with previous experimental studies. In the case of NaCl, the collection efficiencies depend significantly on the stress–strain characteristics of the crystal. Our results suggest that, in addition to particle phase and impact velocity, anisotropy of the elastic properties and brittleness are key factors in controlling the adhesion and bounce of soli...

Direct-drive implosion experiments on the GEKKO XII laser (9 kJ, 0.5 μm, 2 ns) with deuterium and tritium (DT) exchanged plastic hollow shell targets demonstrated fuel areal densities (ρR) of ˜0.1 g/cm2 and fuel densities of ˜600 times liquid density at fuel temperatures of ˜0.3 keV. (The density and ρR values refer only to DT and do not include carbons in the plastic targets.) These values are to be compared with thermonuclear ignition conditions, i.e., fuel densities of 500–1000 times liquid density, fuel areal densities greater than 0.3 g/cm2, and fuel temperatures greater than 5 keV. The irradiation nonuniformity in these experiments was significantly reduced to a level of ρR was directly measured with the neutron activation of Si, which was originally compounded in the plastic targets. The fuel densities were estimated from the ρR values using the mass conservation relation, where the ablated mass was separately measured using the time-dependent X-ray emission from multilayer targets. Although the observed densities were in agreement with one-dimensional calculation results with convergence ratios of 25–30, the observed neutron yields were significantly lower than those of the calculations. This suggests the implosion uniformity is not sufficient to create a hot spark in which most neutrons should be generated.

A robot is developed which is able to climb on a perpendicular branched piping and moves on the ceiling in the piping with the radio control. This inspection robot adsorbs to the piping using the magnetic adsorption force of a magnetic crawler and moves in piping. Therefore, the crawler should be composed of magnets that have optimal adsorption force. In order to design the crawler, the magnetic adsorption force is analyzed, and the design method of the inspection robot in the piping is shown. The robot mounts a radio control unit and a compact radio camera so as to inspect inside of piping. To validate it, a compact crawler type radio control robot is made, and traveling performance or inspection performance in the piping is examined.

The distribution of two-dimensional velocity aberration is off-centered by 5 to 6 microradians in lunar laser ranging, due to the stable measurement geometry in the motion of the Earth and the Moon. The optical responses of hollow-type retroreflectors are investigated through numerical simulations, especially focusing on large-size, single-reflector targets that can ultimately minimize the systematic error in future lunar laser ranging. An asymmetric dihedral angle offset, i.e. setting unequal angles between the three back faces, is found to be effective for retroreflectors that are larger than 100 mm in diameter. Our numerical simulation results reveal that the optimized return energy increases approximately 3.5 times more than symmetric dihedral angle cases, and the optimized dihedral angle offsets are 0.65–0.8 arcseconds for one angle, and zeroes for the other two angles.

In the present report, an effective hands-on treatment for a corneal dermoid that extended to the third eyelid, in the left eye of a Japanese Black calf is described. Xylazine sedation and local infiltration anesthesia with 2% lidocaine on the upper and lower eyelids as well as the third eyelid, in combination with topical anesthesia was performed. A Weitlaner retractor allowed immobilizing the patient’s eyeball during surgery, and superficial lamellar keratectomy was performed to surgically excise the mass. A temporary tarsorrhaphy was placed in order to allow the surgical corneal wound to heal as well as to treat keratitis. After an uneventful postoperative recovery, complete cure 70 days post-operatively was achived. This hands-on method represents a practical and effective treatment for ocular dermoids in calves.

A 7-year-old, 4.2-kg intact male toy poodle was presented to the referring veterinarian with a persistent penile erection and secondary paraphimosis. A full-thickness longitudinal incision was made in the prepuce to release strangulation by the preputial orifice. Castration was also performed. However, the persistent erection did not resolve, which suggested idiopathic priapism. Although prescrotal or scrotal urethrostomy was considered, these procedures commonly have complications, such as severe hemorrhage, stricture of the urethral opening, urine scalding, and abnormal cosmetic appearance. Therefore, preputial reconstruction and urethrostomy were performed following amputation of the penis. A V-Y skin plasty was performed to retract the prepuce caudally. Two triangles of preputial skin at the middle of the prepuce were removed to shorten the prepuce. A 6-Fr catheter was kept in place for 9 days after surgery to prevent stricture formation and to divert urine during initial healing. After surgery, the dog was able to urinate through the natural preputial orifice, showing no urine scalding of the urethrostomy site. Six months after surgery, nomajor complications were observed. The owner was satisfied with the functional and cosmetic outcome.

Fish assemblages along marine artificial reefs have been the objects of numerous studies. Most of them distinguish resident from transient species according to their habitat association level. Despite its wide use, this distinction presents practical complications for two main reasons: first, the method used for assessing habitat association level may cause mistakes, and second, no objective method has been proposed thus far to determine the habitat association level that should be considered as a boundary between resident and transient species. This paper aims at overcoming these two problems. In order to improve and standardize assessment of habitat association level, we developed a habitat association index (HAI) whose calculation requires only presence-absence data. By taking into account both species occurrence rate and occurrence patterns, our index minimizes the risk of erroneously perceiving species as being equally associated to a habitat. In order to distinguish between resident and transient species objectively, we propose to plot HAI against occurrence rate and then seek the combination providing the most significantly different groups with reference to the relation between these two variables. Using two different datasets collected along Japanese artificial reefs and comparing the results with the ones obtained through an alternate method consisting of plotting persistence against maximum abundance and looking for a major gap along the persistence axis, we demonstrate the effectiveness of this two-step method.

Erbium is considered as a slow burnable poison suitable for use in light water reactors (LWRs). Addition of a small amount of Er 2 O 3 to all UO 2 pellets will make it possible to develop super high burnup fuels in Japanese nuclear facilities which are now under the restriction of the upper limit of 235 U enrichment. When utilizing the (U,Er)O 2 fuels, it is very important to understand the thermal and mechanical properties. Here we show the characterization results of (U 1―x Er x )O 2 (0 ≤ x ≤ 0.1). We measured their thermal and mechanical properties and investigated the effect ofEr addition on these properties of (U,Er)O 2 . All Er completely dissolved in UO 2 , and the lattice parameter decreased linearly with the Er content. Both the thermal conductivity and Young's modulus of (U,Er)O 2 decreased with the Er content. These results would be useful for us in evaluating the performance of the (U,Er)O 2 fuels in LWRs.

We prepared polycrystalline pellets of (U,Y)O 2 , containing YO 1.5 up to 11 mol.%. We performed indentation tests on the pellets, and evaluated the Young’s modulus and hardness. We measured the heat capacity and the thermal diffusivity, and evaluated the thermal conductivity. We succeeded in evaluating the effect of Y content on the thermophysical properties of (U,Y)O 2 . We revealed that the Young’s modulus, hardness, and thermal conductivity of (U,Y)O 2 decreased with increasing the Y content.

The mass extinction at the K/P (Cretaceous–Paleogene) boundary was caused by an extraterrestrial impact and the following abrupt climate/environment change. In this study, numerical simulations of asteroid/comet impact on the oceanic crust of the earth are carried out by using the hydrocode AUTODYN-2D (ANSYS, Inc.). The objective of this work is to estimate how much impact debris is ejected into the atmosphere. Therefore the accumulations of ejected mass originating from different sources were calculated as functions of time at different altitudes. It is found that about 50 tera-tons of seawater and 35 tera-tons of crust are ejected when a 10 km diameter asteroid collides on the Earth with the speed of 20 km/s. The values increase to 240 and 175 tera-tons when the asteroid diameter is increased to 20 km. It is also demonstrated that a typical comet disintegrates and bounces back into the atmosphere due to small density, while much heavier asteroids do not recoil much.

We used a three-year (1998–2000) dataset of TRMM Precipitation Radar observations to investigate the scaling properties of spatial rainfall fields. This dataset allows consideration of spatial scales ranging from about 4.3 km to 138 km and short temporal scales corresponding to the sensor overpasses. The focus is on the marginal spatial moment scaling, which allows estimation of the scaling parameters from a single scene of data. Here we present a global perspective of the scaling properties of tropical rainfall in terms of its spatial variability, atmospheric forcing, predictability, and applicability. Our results reveal the following: 1) the scaling parameters exhibit strong variability associated with land/ocean contrast and mean precipitation at the synoptic scale; 2) there exists a one-to-one relationship between the scaling parameters and the large-scale spatial average rain rate of a universal functional form; 3) the majority of the scenes are consistent with the hypothesis of scale invariance at the moment orders of 0 and 2; 4) relatively there are more scale-invariant rain scenes over land than over ocean; and 5) for the scenes that are non-scale-invariant, deviation from scale-invariance mainly arises from the increasingly intermittent behavior of rainfall as spatial scale decreases. These results have important implications for the development and calibration of downscaling procedures designed to reproduce rainfall properties at different spatial scales and lead to a better understanding of the nature of tropical rainfall at various spatial resolutions.

Neodymium mononitride (NdN) pellets with various porosities were prepared by a spark plasma sintering (SPS). The thermal expansion, specific heat capacity and thermal conductivity were measured and compared with those of uranium mononitride (UN), because NdN exists in the irradiated nitride fuels. The thermal expansion and specific heat capacity of NdN were very similar to those of UN. The thermal conductivity of the porosity-free NdN was estimated from the porosity dependence of the thermal conductivity. Unlike the case of the thermal conductivity of UN, that of NdN decreased with increasing temperature.

To explore the variation of the light-regulated genes during complementary chromatic acclimation (CCA), we determined the complete genome sequence of the cyanobacterium Geminocystis sp. strain NIES-3708. Within the light-regulated operon for CCA, we found genes for phycoerythrin but not phycocyanin, suggesting that this cyanobacterium modulates phycoerythrin composition only (type II CCA).

The cyanobacterium Geminocystis sp. strain NIES-3709 accumulates a larger amount of phycoerythrin than the related NIES-3708 strain does. Here, we determined the complete genome sequence of the NIES-3709 strain. Our genome data suggest that the different copy number of rod linker genes for phycoerythrin leads to the different phycoerythrin contents between the two strains.

In this study, numerical simulations of asteroid/comet impact on the earth were carried out by using the hydrocode AUTODYN-2D (Century Dynamics Inc.). The ejected mass into the atmosphere originated from different sources was recorded at different altitudes as a function of time. It is claimed that the mass extinction at the Permian–Triassic (P/T) boundary was caused by an extraterrestrial impact and the following abrupt climate/environment change. The objective of this work is to substantiate the claim with numerical analysis. It is demonstrated that the materials from different origins are splashed into the atmosphere and that the crater size is a function of the diameter as well as the kinetic energy of the impactor. The effect of impact angle to the appearance of ejected materials is also investigated using two-dimensional plane strain model.

The molecular dynamics (MD) calculation was performed for americium-containing mixed oxide fuels, (U0-7--x Pu0.3Am x )O2 (x=0,0.016; 0.03; 0.05; 0.1; 0.15), in the temperature range from 300 to around 2,500 K to evaluate the lattice parameter, heat capacity and thermal conductivity. The MD results reveal that the calculated heat capacity and thermal conductivity are at a similar level in the entire composition range, in other words they are scarcely influenced by adding americium up to 15%. This behavior was examined from a view point of a phonon-impurity scattering mechanism.

The solid-phase reactive epitaxial growth processes and structures of Er/Si(100) thin films were investigated by coaxial impact-collision ion scattering spectroscopy (CAICISS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The as-deposited Er film grown at room temperature was transformed into crystalline rectangular-shaped islands after annealing at 900 °C. These islands have a hexagonal AlB2-type structure and the epitaxial relationship is determined to be ErSi2(011¯0)[0001]//Si(100)[011¯]. It has been revealed that the surface of the Er silicide island is terminated with an Er plane.

We have been developing a system for detecting seafloor crustal movement by combining kinematic GPS and acoustic ranging techniques. A linear inversion method is adopted to determine the position of seafloor stations from coordinates of a moving survey vessel and measured travel times of acoustic waves in seawater. The positioning accuracy is substantially improved by estimating the temporal variation of the acoustic velocity structure. We apply our method to the ranging data acquired at the seafloor reference point, MYGI, located off Miyagi Prefecture, in northeast Japan, where a huge earthquake is expected to occur in the near future. A time series of horizontal coordinates of MYGI obtained from seven campaign observations for the period 2002–2005 exhibits a linear trend with a scattering rms of about 2 cm. A linear fit to the time series gives an intraplate crustal velocity of more than several centimeters per year towards the WNW, which implies strong interplate coupling around this region. The precision of each campaign solution was examined at MYGI and other seafloor reference points along the Nankai Trough through comparison of independent one-day subset solutions within the campaign. The resultant repeatability looks to be well-correlated with the temporal and spatial stability of the acoustic velocity structure in the seawater depending on the region as well as the season.

Objective Interferon alpha (IFN-α) is a key cytokine associated with systemic lupus erythematosus (SLE). IFN-α induces the expression of CD64 on monocytes (mCD64). Although enhanced mCD64 expression has been reported in patients with SLE, it has never been assessed quantitatively. The aim of this study was to investigate whether or not mCD64 expression correlates with SLE disease activity. Methods The mCD64 expression levels were assessed quantitatively in 40 patients with active or inactive SLE by using flow cytometry. The mCD64 expression levels were subsequently compared with the SLE disease activity index (SLEDAI) and levels of existing SLE activity biomarkers, such as anti-DNA antibody, complements, and so on. Results The mCD64 expression was significantly higher in active disease than in inactive disease SLE (median molecules/cell, interquartile range: 34,648, 8174–24,932 and 20,865, 6357–21,503, respectively; p Conclusion The mCD64 expression is a simple and useful biomarker for evaluating disease activity in patients with SLE.

Amorphous carbon (a-C) films have been deposited on Si(100) substrate using RF magnetron system in order to investigate the electron field emission properties. The a-C films were treated by gas plasma at room temperature. Surface morphologices and structural properties of the a-C films before and after plasma treatment were observed by scanning electron microscopy and Raman spectroscope, respectively. Structural properties and surface morphology of the a-C films were changed by plasma treatment. The emission properties can be improved by the plasma treatment according to the contents of nitrogen on the a-C films which is varied by plasma treatment time. Before the plasma treatment, the a-C films are found to have a threshold field of 14 V/m, but the a-C film treated by plasma for 30 min exhibit threshold field as low as 6.5 V/m.

This study presents a method for controlling the number density of vertically aligned carbon nanotubes (CNTs) by dc bias sputtering. The working gas was the mixture of N2 and Ne with a total flow rate of 30 sccm. It was found that the number density of aligned CNTs decreased as the content of Ne gas in the gas mixture increased. The field emission properties of aligned CNTs were measured. The lowest threshold electric field of 4.63 V/μm was obtained for the aligned CNTs with a number density of 2.4×109/cm2, which corresponds to 15 sccm of Ne gas. The result shows that there is an optimal number density of aligned CNTs for field emission since the field enhancement factor is affected by a screening factor.

Using Ar plasama and Fe-phthalocyanine, carbon nanofibers have been synthesized at a low temperature. Fe-phthalocyanine was used as a source material for this process. The carbon nanofibers were grown in random orientation with a diameter of about 100 nm and length up to 10 on Si substrate. The synthesized carbon nanofibers exhibited excellent field emission characteristics. Protrusions with a nanometer size are observed at an angle of 60with respect to the nanofiber axis. Furthermore, we found the selective growth of nanofibers on a scratched substrates.

First-principles total-energy calculations are performed for the low-temperature ordered phase of solid C60 in the wide range of lattice parameter. The intermolecular potential obtained from these calculations is successfully modeled in terms of the interaction between carbon atoms on different C60 molecules and the multipole Coulombic interaction between molecules. This model enables us to calculate structural and thermodynamic properties of both the orientationally ordered and disordered phases in a consistent manner. We find that the equation of state at finite temperature obtained for this potential is not in good agreement with experiments and the intermolecular potential is much shallower than that expected from the experimental heat of sublimation. These discrepancies are interpreted as arising from the limited capability of the density-functional calculations to appropriately incorporate the effect of electron correlations at large separation, which is responsible for the long-range behavior of th...

We have analysed retrospectively the relationship between the axial parameters of alignment of the lower limb and the recurrence of varus deformity after high tibial osteotomy. We studied 29 patients (37 knees) with a mean age at surgery of 66 years. The mean follow-up was for 7.4 years (5 to 10.5). Recurrence of varus deformity was defined as an increase in the femorotibial angle of 3° or more, compared with that obtained six months after the operation. There were four patients (four knees) with recurrence of varus deformity. They had a greater varus inclination of the distal femur than those without varus recurrence. An association between varus inclination of the distal femur and horizontal obliquity of the joint surface was observed. Excessive obliquity prevents the shift of weight-bearing to the lateral compartment, and may cause a recurrence of varus deformity after high tibial osteotomy.

The active form of human blood coagulation factor X (FXa, EC 3.4.21.6) showing N-alpha-Benzoyl-L-isoleucyl-L-glutamyl-L-glycyl-L-arginine- p-nitroanilide (S-2222) hydrolyzing activity was first detected in human semen (seminal plasma) by affinity chromatography using anti-human coagulation factor X, and this enzyme activity was inhibited by anti-human FX. This enzyme has been associated with the human coagulation factor X (FX) in human semen (seminal plasma) by Western blot analysis, and the molecular mass of mature FX was also estimated to be 59 KDa by SDS-PAGE and Western blot analysis.

Dry-thermophilic anaerobic co-digestion (DTAD) can be used to treat forage rice straw and pig manure and generate biogas as an energy source. Solid residue produced from DTAD process can be used as a fertilizer in forage rice fields, while addition of the residue could increase methane (CH4) and nitrous oxide (N2O) emissions from the soil. We evaluated the effects of adding DTAD residue and water management on CH4 and N2O emissions from a forage rice field. Three treatments were evaluated: (a) 100 kg N · ha−1 chemical fertilizer and continuous flooding (CC); (b) residue addition (300 kg N · ha−1 DTAD residue) with continuous flooding (RC); and (c) residue addition with intermittent irrigation (RI). RC and RI showed higher CH4 fluxes than CC throughout the growing period. After a midsummer drainage, RI showed higher soil Eh values and lower CH4 fluxes (mean, 7.6 mg C · m−2 · h−1) than those in RC (mean, 18.6 mg C · m−2 · h−1). Abundance of mcrA gene copy number was not different between RC and RI, suggesting CH4 flux was reduced by suppression of methanogenic activity by intermittent irrigation. Cumulative CH4 emissions during the cultivation period were 105, 509, and 306 kg C · ha−1 in CC, RC, and RI, respectively. N2O fluxes were within detection limits in all treatments. Our results, to our knowledge, are the first to show greenhouse gas emission from forage rice fields supplemented with DTAD residue and of the effectiveness of water management in CH4 mitigation.