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A 74-year-old man with interstitial lung disease (ILD) underwent surgical excision of a growing retroperitoneal tumor and was diagnosed with spindle cell sarcoma. Just after the surgery, skin eruption and muscle weakness emerged. Based on his symptoms and examination findings, we diagnosed him with anti-synthetase syndrome (ASS) with positive anti-glycyl-transfer ribonucleic acid synthetase antibody (anti-EJ) as paraneoplastic syndrome. Immunosuppressive treatments kept his progressing ILD stable for 21 months, although an expanding lung metastatic lesion from primary sarcoma was detected. Measurements of myositis-specific antibodies may enable the prediction of the efficacy of immunosuppressive treatments for paraneoplastic syndrome, even if the primary disease becomes progressive., Internal Medicine, 59(16), pp.2071-2076; 2020

The contributions of the complement system have been elucidated in the process of solid organ transplantation, including kidney transplantation. However, the role of complement in liver transplantation is unknown. We sought to elucidate the time-dependent changes of peritransplantational serum complement levels and the relationships with posttransplant outcomes and other immunological biomarkers. We enrolled 82 patients who underwent living-related donor liver transplantation (LDLT). Nine patients (11%) died within 90 days after LDLT (non-survivors). The following immunomarkers were collected preoperatively and at 1, 2, and 4 week(s) after LDLT: serum C3, C4, immunoglobulin G (IgG), and peripheral blood leukocyte populations characterized by CD3, CD4, CD8, CD16, CD19, CD20, CD22, and CD56. Consequently, C3 and C4 increased time-dependently after LDLT. Preoperatively, C3 was negatively correlated with the MELD score, Child–Pugh score, CD16-positive leukocyte percentage, and the CD56-positive leukocyte percentage. Non-survivors had lower levels of C3 at 2 weeks in comparison to survivors (median [interquartile range]: 56 [49-70] mg/dL vs. 88 [71-116] mg/dL, p=0.0059). When the cutoff value of C3 at 2 weeks to distinguish non-survivors was set to 71 mg/dL, the sensitivity, specificity, and area under the ROC curve were 87.5%, 75.0%, and 0.80, respectively. A principal component analysis showed an inverse relationship between the C3 and C4 levels and the percentage of CD8-, CD16-, and CD56-positive leukocytes at 1 and 2 week(s). All non-survivors were included in the cluster that showed higher percentages of CD8-, CD16-, and CD56-positive leukocytes at 2 weeks. In conclusion, we demonstrated the relationship between complement, outcomes, and other immunomarkers in LDLT and suggested the usefulness of C3 at 2 weeks after LDLT in distinguishing the mortality.

BackgroundLupus nephritis (LN) is a major risk factor for overall morbidity and mortality in systemic lupus erythematosus (SLE).MethodsWe retrospectively analyzed cases of proliferative and membranous LN patients who underwent a renal biopsy at our hospital in 1993–2016. We analyzed the association between complete renal response (CR) rates at 12 months after induction therapy and predictive factors for CR and their association with renal flares.ResultsOf the 95 cases analyzed, we were able to track the therapeutic responses of 81 patients at 12 months after their induction therapy. The median follow-up duration after renal biopsy was 51 months (interquartile range: 16.5–154.5 months). The Cox proportional hazards model showed that, compared to not attaining CR at 12 months, the attainment of CR at 12 months was correlated with being free from renal flares. The multivariate logistic analysis revealed that the predictive factors for CR at 12 months were the anti-La/SSB antibodies (U/ml) (odds ratio (OR) 1.22, 95% confidence interval (CI) 1.01–1.63, p = 0.0220), blood urea nitrogen (BUN) (OR 0.68, 95% CI 0.44–0.90, p = 0.00048) and serum β2 microglobulin (MG) (OR 0.26, 95% CI 0.06–0.74, p = 0.00098) levels.ConclusionsAmong LN patients, being free from renal flares was associated with attaining CR at 12 months after induction therapy. Anti-La/SSB antibodies were a positive predictive factor, and BUN and serum β2MG levels were negative predictive factors of CR at 12 months.

Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Japan Organization of Occupational Health and Safety onbehalf J3D Introduction Improvements in cardiovascular imaging have contributed to the accurate diagnosis and treatment of cardiovascular diseases. In recent years, we can find a new demand from surgical departments, i.e., 3D heart models of patients for preoperative simulations. However, a 3D surgical model needs a detailed segmentation of heart structures from clinical images because these details are essential for achieving accurate polygon data of an exact 3D model. Thus, in most cases, manual segmentation is required for complicated heart shapes such as the chamber wall, valves, and papillary muscles, which causes a prolonged duration time. Purpose We aim to achieve an automated heart segmentation using a convolutional neural network (CNN) trained using deep learning techniques for the rapid creation of 3D surgical heart models of individual patients. Methods We constructed our original CNN program based on the latest artificial intelligence techniques and trained it to extract shapes of the heart from cardiac computed tomography (CT) images. The training data was 361 slices selected from CT scans of 10 patients. We used data augmentation to increase the amount and diversity of the data into 24,052 slices. The training result with the best Intersection over Union (IoU), one of the evaluation metrics used in deep learning, was saved. Finally, we used the best-trained CNN to construct 3D polygon data of two surgical cases of hypertrophic obstructive cardiomyopathy (HOCM) for preoperative assessments. Results The IoU attained 0.85 after deep learning. The time required to complete the 3D polygon data for the first HOCM case was 5 minutes for segmentation by the trained CNN and 3 hours for data correction by a human operator. Similarly, the time required for the second case was 5 minutes for segmentation without manual correction. We had to correct the segmentation for the first case because we needed an exact 3D model for the preoperative assessment (Fig. 1). According to our records of the other eight 3D heart models in the lab, the work for a 3D polygon shape from CT images needs a median 30 hours (quartiles 23-50 hours) when the procedure is fully manual and non-continuous with breaks in between. Conclusion The CNN-based segmentation aided the constructing heart shapes from cardiac CT images of preoperative patients. Although the performance, reaching IoU of 0.85, was insufficient for fully automatic segmentation, the methodology can shorten the process duration from several hours to several minutes for detailed segmentation of heart structures. We previously applied the CNN-based segmentation to the aorta, aortic stenosis valves, and atheromatous plaque in clinical images, demonstrating adequate segmentation performance. The proposed methodology can be applied as a fundamental technology of cardiovascular imaging for obtaining the actual structures of a target object as 3D coordinate values or a 3D model within a reasonable duration time. Abstract Figure 1

A new High-Temperature Superconducting ECR (HTS-ECR) ion source is under development in Research Center for Nuclear Physics (RCNP), Osaka University. This ion source will be used for production of high intensity proton, deuteron and He ion beams. The HTS-ECR magnets are composed of three solenoid coils and a set of sextupole coils made of REBCO tapes, a high-temperature superconductor. The HTS-ECR ion source is designed to operate at frequency of 2.45 GHz and 10 GHz. Performance test of the HTS coils had been carried out at 31 K and 77 K. This HTS coil technology will be applied to development of a meter-size HTS coil system of a high intensity compact AVF cyclotron. This paper introduces the basic design of the HTS-ECR ion source. The performance test results showed that REBCO solenoids remain superconducting state with a current up to 400 A. Simulation results of the magnetic field and electromagnetic field distributions in a plasma chamber fulfilled the requirements of electron cyclotron resonance conditions at 2.45 GHz and 10 GHz. Simulation result of mirror ratios and electromagnetic field amplitudes are also presented in this paper.

This multicenter phase II N-DOCC-F-C-1701 trial is being planned in order to investigate the efficacy and safety of CPT-11+S-1 +Ramucirumab (IRIS+Rmab), which is anticipated to have a stronger anti-tumor effect than IRIS+Bmab in patients with metastatic colorectal cancer (mCRC) previously treated with oxaliplatin (L-OHP) containing regimen, in consideration of the result of RAISE, FIRIS and some phase II trials of IRIS+Bevacicizumab (Bmab). The number of patients is set at 38 for the statistical analysis, assuming an expected median PFS of 5.0 months (threshold: 3.0 months). The primary endpoint of the study is the progression free survival (PFS), and the secondary endpoints are the overall response rate (ORR), overall survival (OS), adverse events (AE), quality of life (QOL) and review of nausea and vomiting. This trial is registered in the UMIN Clinical Trials Registry as UMIN000028170. We intend to start conducting the trial in September 1, 2017. If this trial meets the endpoint, IRIS+Rmab might be supported as a new optional standard regimen for mCRC.

BACKGROUND Direct support professionals (DSPs) support people with intellectual and developmental disabilities in activities of daily living. DSPs may experience both contentment and struggles with their work. As agencies grapple with their recruitment and retention, understanding DSPs' holistic work experience is important. The Professional Quality of Life (ProQOL) scale assesses multiple domains of work experiences (i.e. compassion satisfaction, burnout and secondary traumatic stress). Despite extensive use across helping professions, the ProQOL is largely absent from DSP research. METHOD This study examined the factor structure of the ProQOL with DSPs. Using secondary data from 495 DSPs, confirmatory factor analysis was conducted to determine if the original three-factor structure holds for this population. RESULTS We confirmed the factorial validity of the ProQOL with the three-factor solution. In the validation process, some modifications were suggested to the model, which also improved the scale reliability. CONCLUSIONS The current study provides initial evidence of the factorial validity of the ProQOL when used with DSPs, as well as recommendations for subsequent improvements and future research.

Background Polymyositis/dermatomyositis (PM/DM) is an autoimmune disease that is sometimes complicated with rapidly progressive interstitial lung disease (RPILD). However, serum and lung biomarkers that can predict RPILD development remain unclear. Objectives To determine potential serum and lung biomarkers that can predict RPILD development in patients with PM/DM-ILD. Methods In total, 49 patients with PM/DM-ILD were enrolled. We measured the serum levels of 41 cytokines/chemokines, ferritin and anti-MDA5 antibody, compared them between the RPILD (n = 23) and non-RPILD (n = 26) groups, and ranked them by their importance through random forest analysis. To distinguish the two groups, we determined biomarker combinations by logistic regression analysis. We also measured the bronchoalveolar lavage fluid (BALF) levels of 41 cytokines/chemokines. Using immunohistochemistry, we examined IL-15 expression in lung tissues. The IL-15 production was also investigated using A549 and BEAS-2B cells. Results The RPILD group had significantly higher IL-15, IL-1RA, IL-6, CXCL10, VCAM-1, anti-MDA5 antibody and ferritin serum levels than the non-RPILD group, but it had a significantly low CCL22 level. Meanwhile, anti-MDA5 antibody, IL-15, CXCL8, CCL22, IL-1RA and ferritin were the best combination to distinguish the two groups. IL-15 and CCL22 were also predictive marker for RPILD development in anti-MDA5 antibody-positive patients. Additionally, the RPILD group had significantly high IL-15 levels in BALF. The lung tissues expressed IL-15, which increased after cytokine stimulation in the A549 cells. Conclusion This study identified a combination of biomarkers predicting PM/DM-RPILD progression, and IL-15 is an important cytokine for predicting RPILD development and reflecting ILD severity.

The complement cascade, especially the alternative pathway of complement, has been shown in basic research to be associated with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). We aimed to elucidate relationships between serum complement components and clinical characteristics in AAV. In a nationwide prospective cohort study (RemIT-JAV-RPGN), we measured the serum levels of C1q, C2, C3, C3b/iC3b, C4, C4b, C5, C5a, C9, factor B, factor D, factor H, factor I, mannose-binding lectin, and properdin in 52 patients with microscopic polyangiitis (MPA) and 39 patients with granulomatosis with polyangiitis (GPA). The properdin level of MPA and GPA was significantly lower than that of healthy donors. The properdin level was negatively correlated with the Birmingham Vasculitis Activity Score (BVAS) (ρ = −0.2148, p = 0.0409). The factor D level at 6 months was significantly positively correlated with the Vasculitis Damage Index (VDI) at 6, 12, and 24 months (ρ = 0.4207, 0.4132, and 0.3115, respectively). Patients with a higher ratio of C5a to C5 had higher neutrophil percentage and serum immunoglobulin G levels, and significantly lower creatinine levels. Cluster analysis divided the MPA and GPA patients into three subgroups. A principal component (PC) analysis aggregated 15 types of complements into alternative pathway-related PC 1 and complement classical pathway and common pathway-related PC 2. The serum levels of properdin and factor D were correlated with the BVAS and the VDI in MPA and GPA, respectively. Our analyses suggested the pathological heterogeneity of MPA and GPA from the aspect of complement components.

Background: Lupus nephritis (LN) is a major determinant of mortality in systemic lupus erythematosus (SLE).Here we evaluated the association between complete renal response (CR) and mortality in LN.Methods: We retrospectively analyzed the cases of 172 of 201 patients with LN for whom data on the therapeutic response at 6 and 12 months after induction therapy were available. The patients underwent a renal biopsy at Nagasaki University Hospital and community hospitals in Nagasaki between the years 1990 and 2016.We determined the CR rates at 6 and 12 months after induction therapy initiation and evaluated the predictive factors for CR and their relationship with mortality. We performed univariate and multivariable competing risks regression analyses to determine the factors predictive of CR. The patients' survival data were analyzed by the Kaplan?Meier method with a log-rank test.Results: The median follow-up duration after renal biopsy was 120 months (interquartile range: 60.3?191.8 months). The 5-, 10-, 15- and 20-year survival rates of our cohort were 99.3, 94.6, 92.0 and 85.4%, respectively. During follow-up, nine patients (5.2%) died from cardiovascular events, infection, malignancy and other causes.The multivariate analysis revealed that the following factors were predictive of CR. At 6 months: male gender (odds ratio (OR) 0.23, 95% confidence interval (CI) 0.08?0.65, p = 0.0028),proteinuria (g/gCr) (OR 0.83, 95% CI 0.71?0.97, p = 0.0098) and index of activity (0?24) (OR 0.84, 95% CI 0.71?0.99, p = 0.0382).At 12 months: male gender (OR 0.25, 95% CI 0.09?0.67, p = 0.0043) and index of activity (0?24) (OR 0.82, 95% CI 0.69?0.98, p = 0.0236). The Kaplan?Meier analysis showed that compared to not achieving CR at 12 months, achieving CR at 12 months was significantly correlated with the survival rate (OR 0.18, 95% CI 0.04?0.92, p = 0.0339). Conclusions: Our results suggest that the survival rate of patients with LN is associated with the achievement of CR at 12 months after induction therapy, and that male gender and a higher index of activity (0?24) are the common predictive factors for failure to achieve CR at 6 and 12 months., Lupus, 28(3), pp.295-303; 2019

Supplemental material, Supplemental Material1 for Factors predictive of long-term mortality in lupus nephritis: a multicenter retrospective study of a Japanese cohort by K Ichinose, M Kitamura, S Sato, K Fujikawa, Y Horai, N Matsuoka, M Tsuboi, F Nonaka, T Shimizu, S Fukui, M Umeda, T Koga, S Kawashiri, N Iwamoto, M Tamai, H Nakamura, T Origuchi, T Nishino and A Kawakami in Lupus

Background Magnetic resonance imaging (MRI) and ultrasound (US) are both useful modality to monitor disease status of RA whereas combination analysis of disease course by both modalities are quite few. Objectives To clarify the predictors of radiographic progression in patients with RA examined by both MRI and US. Methods Thirty-three patients with active RA, managed with a treat-to-target strategy and checked disease activity score every three months along with examination of both MRI and US, were enrolled from June 2010 to June 2016 and observed for 12 months. US of wrist and finger joints was examined every three months, MRI and radiograph were done every six months. US were evaluated by synovitis score of semi-quantitative manner by gray-scale (GS) and power Doppler (PD) proposed from EULAR. In MRI, synovitis, bone oedema and bone erosion were assessed by the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system (RAMRIS). Radiographic bone erosion and joint space narrowing (JSN) were scored by Genant-modified Sharp Score (GSS). Radiographic progression was defined as delta radiographic score >0.5. Multivariate analysis was employed to clarify independent predictors for radiographic progression at 12 month. Results Thirteen patients were treated with methotrexate monotherapy and eighteen were received combination of methotrexate and biologics. Three were given biologic monotherapy. Median of age was 57.0 years and that of disease duration was 9 months. Female was 84.8%, positive rate of RF was 87.1% and that of ACPA was 79.3%. DAS28-CRP was 4.20, total GS score 6.0, total PD score 4.0, MRI synovitis score 6.0, MRI bone oedema score 3.0, MRI bone erosion score 3.0, and GSS score 1.0 at baseline. Radiographic progression was found in 12 patients. Multivariate analysis revealed that high MRI bone oedema score at baseline, high MRI bone oedema score and PD ≧ grade 2 articular synovitis at any joints at 6 month were associated with radiographic progression at 12 months. Clinical indices of DAS28-CRP at any point did not predict radiographic progression compared with MRI or US. Conclusions During treat-to-target strategy, the presence of MRI bone oedema as well as PD ≧ grade 2 articular synovitis are found to be important to predict radiographic outcome in active RA patients. These imaging indices may be more sensitive to monitor radiographic progression as compared with clinical indices. Disclosure of Interest None declared

Background We previously reported that the presence of autoantibodies, magnetic resonance imaging (MRI) bone oedema, ultrasound (US) power Doppler (PD) x grade 2 articular synovitis are indispensable markers to predict the development of RA from undifferentiated arthritis whereas combination analysis used by the above variables, focusing on very early phase of arthritis, remains to be done in our cohort. Objectives To investigate and re-confirm the diagnostic performance of autoantibodies, MRI findings and US findings toward early RA from NAGASAKI EARLY ARTHRITIS COHORT. Methods One hundred and three patients, suffering arthralgia less than 6 months and examined by both MRI and US of wrist and finger joints, were selected from NAGASAKI EARLY ARTHRITIS COHORT dating from September 2009 to August 2017. US were evaluated by synovitis score of semi-quantitative manner by gray-scale (GS) and power Doppler (PD) proposed from EULAR. In MRI, synovitis, bone oedema and bone erosion were assessed by the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system (RAMRIS). After univariate analysis, multivariate analysis was employed to clarify the diagnostic predictors of early RA. Results Median of age was 60 years and that of symptomatic duration was 2 months. Female was 68.9%, positive rate of RF was 64.7% and that of ACPA was 47.1%. Total GS score was 4.0, total PD score 2.0, MRI synovitis score 3.0, MRI bone oedema score 0, MRI bone erosion score 0. Seventy patients were diagnosed as early RA during follow-up periods. A univariate analysis showed ACPA, CRP, MMP-3, fulfilment of 2010 ACR/EULAR criteria, MRI synovitis score, MRI bone oedema score, total GS score, total PD score and PD x grade 2 articular synovitis were associated with early RA. Multivariate analysis revealed ACPA and PD x grade 2 articular synovitis at any joints were independent predictors toward diagnosis of early RA. Conclusions Our present study re-confirms the importance of ACPA, PD x grade 2 articular synovitis and MRI bone oedema, especially the former two, to predict the development of early RA from undifferentiated arthritis patients. Disclosure of Interest None declared

Background In IgG4 related disease (IgG4-RD), hypocomplementemia is known to be seen. Complement pathways consist of three pathways, classical, alternative, and lectin pathways. Although IgG1 and IgG3 have ability to activate complement, IgG4 is known to be ineffective at activating complement. Objectives We attempted to elucidate which complement pathway is mainly associated with IgG4-RD. Methods Levels of complement elements and complement-associated elements, C1q, C2, C3, C3b/iC3b, C4, C4b, C5, C5a, C9, Factor D, Factor I, mannose-binding lectin (MBL), Factor B, Factor H, and properdin in preserved sera of patients with IgG4-RD at diagnosis and at remission were measured using multiplex bead-based assay. We compared complement levels at diagnosis of IgG4RD patients with those of sex-matched healthy donors. Results This study included 28 IgG4-RD patients and sex-matched 28 healthy donors. The median age at diagnosis and healthy donors’ age were 65 [interquartile range (IQR): 55–70] and 64 (IQR:56–73), respectively. Patients with IgG4-RD at diagnosis had significantly higher levels of C5 and C5a [33347 ng/mL vs. 30375 ng/mL (median), p=0.0293, 16417 pg/mL vs. 7083 pg/mL, p Conclusions The classical complement pathway may be associated with IgG4-RD rather than the alternative pathway and the lectin pathway based on results except for Factor D. Disclosure of Interest None declared

Background Our previous nation-wide survey showed the clinical manifestations and prevalence of Japanese Familial Mediterranean Fever (FMF) patients. However, the clinical differences between young-onset FMF (YOFMF), adult-onset FMF (AOFMF), and late-onset FMF (LOFMF) have not been yet clarified. Objectives We sought to compare between the clinical profile of patients with AOFMF, LOFMF and YOFMF and to determine the clinical characteristics of them. Methods We enrolled consecutively 395 patients in 2006–2017. Mutation detection in exons 1, 2, 3, and 10 of the MEFV gene was performed. We defined YOFMF, AOFMF and LOFMF as the onset of FMF MEFV gene among these three groups. Results The median age at the onset of YOFMF, AOFMF and LOFMF were 12.5, 28 and 51 years old respectively. A family history of FMF and a mutation in exon 10 of the MEFV gene were significantly more frequent in groups with younger onset ([YOFMF 28%, AOFMF 17%, LOFMF 12%; p Conclusions Our results suggest that older onset FMF had a lower percentage of mutations in exon10 of the MEFV gene and predominantly presented arthritis and muscle pain during the attacks. It is thus important to distinguish them from other inflammatory diseases such as gout, adult Still’s disease, and infectious arthritis. Disclosure of Interest None declared

Background The precise cytokine networks in the serum of individuals with adult onset still disease (AOSD) that are associated with its pathogenesis have been unknown. Serum levels of interleukin (IL)−1β, IL-6 and IL-18 have been reported as useful serum biomarkers for diagnosis and disease evaluation among AOSD patients,1 2 but these cytokines are also elevated in other inflammatory diseases including severe infection. Objectives We attempted to identify specific biomarkers to distinguish AOSD from sepsis. Methods We measured serum levels of 45 cytokines in 66 AOSD patients, 17 sepsis patients and 133 age-matched controls by multi-suspension cytokine array. Japan College of Rheumatology-certified rheumatologists diagnosed with AOSD based on the Yamaguchi criteria. Cytokines were ranked by their importance by a multivariate classification algorithm. We performed a logistic regression analysis to determine specific biomarkers for discriminating AOSD from sepsis patients. To identify specific molecular networks, we performed a cluster analysis of each cytokine. Results Serum fibroblast growth factor 2 (FGF-2), vascular endothelial growth factor (VEGF), granulocyte-colony stimulating factor (G-CSF), and IL-18 levels were significantly elevated in the AOSD group versus the sepsis group. Multivariate classification algorithms followed by a logistic regression analysis revealed that the measurement FGF-2 distinguished AOSD patients from sepsis patients with the highest accuracy (cut-off value=28.5 pg/mL, sensitivity 100%, specificity 88.2%, accuracy 96.7%). Conclusions We have demonstrated that FGF-2 can be the best biomarker for differential diagnosis between AOSD and sepsis based on the measurement of multiple cytokines. Although the differential diagnosis between rheumatic diseases and infectious conditions is a great challenge in clinical practice, these findings help to improve the diagnostic performance of AOSD in daily practice. References [1] Clin Exp Rheumatol. 1996Nov–Dec;14(6):653–5. [2] Rheumatology (Oxford)2016Dec;55(12):2237–2247. Disclosure of Interest None declared

Background In antineutrophil cytoplasm autoantibody (ANCA)-associated vasculitis (AAV), involvement of complements, especially alternative pathway of complement, has been reported in researches using mouse models. In human, while some studies have identified levels of C3 as a renal prognostic factor, entire complement factors in alternative pathway have not been evaluated. Objectives To evaluate complement profiles of AAV patients at diagnosis and at 6 months after treatments (Month 6). Methods In total, 91 incident cases of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) based on the European Medicines Agency algorithm were enrolled. They are a part of participants of the Japanese nationwide, prospective, inception cohort study from 22 tertiary Japanese institutions (RemIT-JAV-RPGN). Multiplex complement bead assays to measure levels of C1q, C2, C3, C3b/iC3b, C4, C4b, C5, C5a, C9, Factor D, Factor I, MBL, factor B, factor H, and properdin were performed using preserved sera at diagnosis and at Month 6. We compared complement levels at diagnosis of AAV patients with those of age- and sex-matched healthy donors, and compared those of the AAV patients at diagnosis and Month 6. Results Seventy-two of 91 patients had serum both at baseline and Month 6. Compared with healthy donors, GPA patients had significantly higher levels of C2, C5a, and Factor B, and significantly lower levels of C3b/iC3b, C4b, and properdin. MPA patients had significantly higher levels of C2 and Factor D, and significantly lower levels of C3b/iC3b, C4, C5, Factor H, and properdin (table 1). At baseline, GPA had significantly higher levels of C4, Factor B and Factor H, and had significantly lower levels of C4b and Factor D compared to MPA. There are no significant differences in levels of C3, C5, Factor D, MBL, and properdin using Wilcoxon signed-rank test between at diagnosis and Month 6 both in GPA and MPA. Factor I significantly decreased at Month 6 only in GPA. Other complement factors significantly decreased at Month 6 both in GPA and MPA. GPA, granulomatosis with polyangiitis; MPA, microscopic polyangiitis; HD, health donor. Conclusions We found some differences in complement factors among GPA, MPA, and healthy donors. There were no differences of levels of C3, C5, Factor D, and properdin, which suggested involvements of alternative pathway, both in GPA and MPA between at diagnosis and Month 6. Disclosure of Interest None declared

Differential cross sections and photon-beam asymmetries for the γ[over →]p→π^{-}Δ^{++}(1232) reaction have been measured for 0.7

Differential cross sections and photon-beam asymmetries for the γ[over →]p→π^{-}Δ^{++}(1232) reaction have been measured for 0.7cosθ_{π}^{c.m.}1 and E_{γ}=1.5-2.95 GeV at SPring-8/LEPS. The first-ever high statistics cross-section data are obtained in this kinematical region, and the asymmetry data for 1.5E_{γ}(GeV)2.8 are obtained for the first time. This reaction has a unique feature for studying the production mechanisms of a pure uu[over ¯] quark pair in the final state from the proton. Although there is no distinct peak structure in the cross sections, a non-negligible excess over the theoretical predictions is observed at E_{γ}=1.5-1.8 GeV. The asymmetries are found to be negative in most of the present kinematical regions, suggesting the dominance of π exchange in the t channel. The negative asymmetries at forward meson production angles are different from the asymmetries previously measured for the photoproduction reactions producing a dd[over ¯] or an ss[over ¯] quark pair in the final state. Advanced theoretical models introducing nucleon resonances and additional unnatural-parity exchanges are needed to reproduce the present data.

Supplemental material, Supplementary Figure for The efficacy of adjunct tacrolimus treatment in pregnancy outcomes in patients with systemic lupus erythematosus by K Ichinose, S Sato, Y Kitajima, Y Horai, K Fujikawa, M Umeda, S Fukui, A Nishino, T Koga, S Y Kawashiri, N Iwamoto, M Tamai, H Nakamura, T Origuchi, I Yasuhi, H Masuzaki and A Kawakami in Lupus

Supplemental material, Supplementary Table for The efficacy of adjunct tacrolimus treatment in pregnancy outcomes in patients with systemic lupus erythematosus by K Ichinose, S Sato, Y Kitajima, Y Horai, K Fujikawa, M Umeda, S Fukui, A Nishino, T Koga, S Y Kawashiri, N Iwamoto, M Tamai, H Nakamura, T Origuchi, I Yasuhi, H Masuzaki and A Kawakami in Lupus

Background Monocytes can differentiate into either proinflammatory, microbicidal M1 macrophage or anti-inflammatory M2 macrophage subtypes. In addition to macrophages, regarding monocyte subsets, M1 monocytes and M2 monocytes mirroring the M1/M2 macrophage polarization concept were suggested. Little is known regarding the relationships between osteoclastogenesis and M1/M2 monocyte subsets. Objectives We investigated the relationships among M1 monocytes, M2 monocytes, osteoclast differentiation ability and clinical characteristics in patients with rheumatoid arthritis (RA). Methods Peripheral blood mononuclear cells (PBMCs) were isolated from RA patients and healthy donors, and we then investigated the number of M1 monocytes or M2 monocytes by fluorescence-activated cell sorting. We defined positive CD14, CD68 and CCR2 monocytes as M1 monocytes, and in separate tubes, we defined positive CD14, CX3CR1 and CD163 or CD206 monocytes as M2 monocytes. We also obtained and cultured CD14-positive cells from PBMCs from RA patients and healthy donors to investigate osteoclast differentiation in vitro. We defined osteoclasts as tartrate-resistant acid phosphatase (TRAP) staining-positive cells with >3 nuclei. We counted the osteoclasts in the whole wells of a 96-well dish. Pit formation assays were performed to evaluate function of osteoclasts. Results Forty RA patients and 20 healthy donors were included. Twenty-two patients (55%) were ACPA-positive. The median M1/M2 ratio was 0.59 (0.31–1.11, IQR). There were no significant differences between the RA patients and healthy donors. There was a positive correlation between the M1/M2 ratio and the differentiated osteoclast number in vitro in RA patients (ρ=0.81, p The ACPA-positive patients had significantly higher M1/M2 ratio in vivo (p=0.028) (E) and significantly greater numbers of osteoclasts in vitro (p Multivariable regression analysis revealed that the M1/M2 ratio was the sole significant contribution factor to in vitro osteoclastogenesis (β-coefficient 16.3, p RA patients with M1/M2 ratio >1 (having relatively more M1 monocytes) had higher erythrocyte sedimentation rates (p=0.011) and C-reactive protein (p=0.032) than RA patients with M1/M2 ratio ≤1. M1-dominant monocytes in vitro produced higher concentrations of IL-6 upon stimulation with lipopolysaccharide than M2 monocytes (p=0.032). Conclusions The M1/M2 ratio is strongly correlated with the in vitro differentiation of osteoclasts in patients with RA. The RA patients with positive ACPA had higher M1/M2 ratio and higher numbers of osteoclasts. M1 and M2 monocyte subsets may become a new target of treatments for RA. Disclosure of Interest None declared

Background The hallmarks of rheumatoid arthritis (RA) is the expansive of fibroblast-like synovial cells (FLS) in affected joints, causing joint destruction. FLSs are resistant to programmed cell death resulting in aggressive, invasive phenotype like a cancer invades and the hyperplastic synovial tissue destroys cartilage and bone. Therefore inhibition of FLS proliferation and is one of the therapeutic targets of RA. MicroRNAs (miRNAs), a group of small non-coding RNAs, have been shown to regulate cell differentiation through regulation of gene expression post-transcriptionally. Recently, several studies reported anti-cancer drugs modulate miRNA expression and that have been considered as one of important mechanism of cellular action to drug1,2. Objectives To investigate the changes in microRNA expression profiles in response to MTX. Methods RA-FLS was treated with MTX with 1nM 48 hours, that could inhibit IL-6 production from RA-FLS. To investigate differentially expressed miRNAs in response to MTX, we performed miRNA array analysis. Expression of miR-887–3p in response to MTX of RA-FLS was analyzed by quantitative real-time PCR. To investigate the functional role of miR-887–3p, RA-FLS was transfected with synthetic precursor miRNA (pre-miR)/inhibitors of miRNA (anti-miR) of miR-887–3p using Lipofectamine and then gene expression microarray was performed. The cytokine/ chemokine production was screened by Multiplex cytokine/chemokine bead assays and confirmed by ELISA. Finally, we analysed migratory activities of RA-FLS by scratch assay. Results After 48 h of treatment with MTX, 7 miRNAs were up-regulated and 6 miRNAs were down-regulated as compared with that of untreated control. Among them quantitative real-time PCR with additional samples confirmed that miR-887–3p was up-regulated in response to MTX treatment of RA-FLS (1.79±0.46 -fold, p Conclusions Our result showed that MTX altered micro RNA expression profiles in RA-FLS. MiR-887–3p might be downstream effector of MTX in suppression of its cytokine production and invasive phenotype. This knowledge may also be useful for the development of novel therapeutic strategies for RA based on other treatments able to boost the cellular reservoir of miR-877–3p. References Potenza N, Mosca N, Zappavigna S et al. MicroRNA-125a-5p Is a Downstream Effector of Sorafenib in its Antiproliferative Activity Toward Human Hepatocellular Carcinoma Cells. J Cell Physiol. 2016 Dec 16. Shah MY, Pan X, Fix LN et al. 5-Fluorouracil drug alters the microRNA expression profiles in MCF-7 breast cancer cells. J Cell Physiol. 2011; 226(7):1868–1878. Disclosure of Interest None declared

Background Kidneys are major organs targeted by antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Clinical manifestations, laboratory data, and prognosis of AAV with renal involvement at diagnosis are not elucidated. Objectives We compared clinical features of AAV with renal involvement with patients without renal involvement. Methods We conducted an observational study of 104 patients with AAV (12 eosinophilic granulomatosis with polyangiitis, 23 granulomatosis with polyangiitis (GPA), 66 microscopic polyangiitis, 3 renal limited vasculitis) between in 2008 to 2016 in Nagasaki University Hospital. Using medical records, we analyzed the patients9 baseline variables, laboratory data, clinical symptoms, and therapeutic outcomes after treatments including episodes of relapses, initiations of dialysis, and death. Renal involvement was defined as the state with estimated glomerular filtration rate 2 or microscopic hematuria (2+ or greater) which were not caused by renal diseases except for AAV. Results Sixty-nine patients had renal involvement. Patients with renal involvement group had higher median age at diagnosis than patients without renal involvement group (75 years vs. 66 years, p 4 /μL vs. 28.7x10 4 /μL). Patients with renal involvement had higher erythrocyte sedimentation rate (78mm/h vs. 20mm/h), MPO-ANCA titers (116 U/mL vs. 58 U/mL) and urine protein levels (0.81 g/gCr vs. 0.15 g/gCr). Patients with renal involvement had lower C3 levels, but CH50 and C4 levels did not differ between in two groups. There were no differences in treatments including doses of prednisolone and use of methylprednisolone pulse and cyclophosphamide between in two groups. Multivariable regression analysis revealed that age at diagnosis is the most significant explanatory variable to renal involvement. Nineteen percent of patients with renal involvement had initiations of dialysis. Multivariable analysis demonstrated estimated glomerular filtration rate at diagnosis is the most significant explanatory variable to initiations of dialysis (p=0.010). Receiver operating characteristic curve showed the cutoff level of estimated glomerular filtration rate to distinguish initiations of dialysis was 37mL/min/1.73 m 2 (sensitivity=79%, specificity=70%, area under the curve=0.80). Assessed by a log-rank test, overall survival rate did not differ between in two groups (p=0.29). Conclusions Patients with renal involvement had higher age at diagnosis. Patients with renal involvement included fewer GPA patients. Patients with renal involvement had lower C3 levels. Estimated glomerular filtration rate at diagnosis is the most significant explanatory variable to initiations of dialysis. Disclosure of Interest None declared

This letter describes how Tripler Army Medical Center Multidisciplinary Sleep Clinic (TAMC Multi-D Sleep Clinic) was established and how it has evolved over the years. This clinic is specifically d...

The $\ensuremath{\phi}\text{\ensuremath{-}}\mathrm{\ensuremath{\Lambda}}(1520)$ interference effect in the $\ensuremath{\gamma}p\ensuremath{\rightarrow}{K}^{+}{K}^{\ensuremath{-}}p$ reaction has been measured for the first time in the energy range from 1.673 to 2.173 GeV. The relative phases between $\ensuremath{\phi}$ and $\mathrm{\ensuremath{\Lambda}}(1520)$ production amplitudes were obtained in the kinematic region where the two resonances overlap. The measurement results support strong constructive interference when ${K}^{+}{K}^{\ensuremath{-}}$ pairs are observed at forward angles but destructive interference for proton emission at forward angles. Furthermore, the observed interference effect does not account for the $\sqrt{s}=2.1\text{ }\text{ }\mathrm{GeV}$ bump structure in forward differential cross sections for $\ensuremath{\phi}$ photoproduction. This fact suggests possible exotic structures such as a hidden-strangeness pentaquark state, a new Pomeron exchange, or rescattering processes via other hyperon states.

The ϕ-Λ(1520) interference effect in the γp→K^{+}K^{-}p reaction has been measured for the first time in the energy range from 1.673 to 2.173 GeV. The relative phases between ϕ and Λ(1520) production amplitudes were obtained in the kinematic region where the two resonances overlap. The measurement results support strong constructive interference when K^{+}K^{-} pairs are observed at forward angles but destructive interference for proton emission at forward angles. Furthermore, the observed interference effect does not account for the sqrt[s]=2.1 GeV bump structure in forward differential cross sections for ϕ photoproduction. This fact suggests possible exotic structures such as a hidden-strangeness pentaquark state, a new Pomeron exchange, or rescattering processes via other hyperon states.

Magnetic drug delivery system (MDDS) is the method which the magnetic seeded drug is injected into a blood vessel and then controlled and accumulated by a magnet located outside of the human body. A high accumulation efficiency of the drug to a local diseased part and reduction in side-effects to normal organs are expected by using MDDS. The most important element in MDDS is a magnetic field generator. The high temperature superconducting (HTS) bulk magnet which can generate high magnetic field and magnetic field gradient extending to a point distant from the magnet in several ten millimeters is necessary to achieve the MDDS. In this study, the computer simulation and model experiment were conducted in order to confirm the applicability of MDDS to ovary of the cow body.

Pleurotus eryngii was cultivated on sugarcane bagasse substrate to enhance the digestibility of bagasse. Effects of culture length on the digestibility and chemical composition were determined. Substrate consisting of bagasse and rice bran was incubated at 24 °C for 35 days under semi-anaerobic conditions then transferred to an incubation room at 17 °C to enable the fruit-bodies to emerge. The average yield of the fruit-bodies at the first flush was 74.3 g/culture bottle. The proportion of residual weight of dry matter in the substrate decreased by 0.242 on day 95, and further by 0.053 between days 95 and 155. The proportion of residual weight of lignin decreased by 0.350 on day 95, and further by 0.066 between days 95 and 155. The in vitro organic matter (OM) digestibility (IVOMD) of the substrate increased from 0.537 on day 0 to 0.693 on day 95. The in vitro digestibility of neutral detergent fiber excluded ash (IVNDFomD) increased from 0.480 to 0.584. The cumulative in vitro gas production (IVGP) for 48 h increased from 144 to 197 ml/g OM. Since there were no differences in IVOMD, IVNDFomD and IVGP between days 95 and 155, it was concluded that 95 days after inoculation was an appropriate culture length, at which spent bagasse substrate could be used as feed for ruminants.

Dispersed generators are being introduced to power systems to secure the electric power supply. However, a short-circuit capacity of the power system increases with the introduction of dispersed generators. As a result, there is concern that a fault current will increase further, and instantaneous voltage sag might be caused. It is proposed to apply a superconducting fault current limiter in the distribution system with dispersed generators to solve these issues. In this paper, the effect of superconducting fault current limiter in this power system is studied by the analysis with EMTP and the confirmation test is conducted with a simulator.

Objective Washing the hands using cleansers with antiseptic materials is the most popular method for hand hygiene and helps maintain health by preventing food poisoning and bacterial infections. However, repeated hand washing tends to induce eczema of the hand, such as dryness, cracking and erythema. Moreover, eczema on the hand leads to increased levels in Staphylococcus aureus (S. aureus) on the skin surface in contrast to expectations. Thus, mild hand cleansers which induce less eczema even with repeated washings are desired. Here, we evaluated the efficacy of a hand cleanser formulated with alkyl ether sulphate (AES), alkyl ether carboxylic acid (AEC) and alkyl glucoside (AG) that contains isopropyl methylphenol (IPMP) on skin symptoms and S. aureus levels. Methods Eczema of the hand and the presence of S. aureus on the skin surface were analysed prior to and following 4 weeks of usage of the hand cleanser. A soap-based hand cleanser with IPMP was used as a reference cleanser. Eczema and cutaneous conditions were evaluated by visual grading, transepidermal water loss (TEWL), stratum corneum moisture-retention ability (MRA) and skin surface pH. Results The repeated use of the soap-based hand cleanser significantly worsened the hand dryness, scaling and cracks on the tips of the fingers and significantly increased the TEWL and decreased the MRA. In contrast, usage of the test cleanser only induced a significant increase in skin dryness but did not induce skin scaling or cracking and did not increase TEWL or decrease the MRA. Corresponding to these changes in skin symptoms, the presence of S. aureus increased the following use of the reference cleanser but not the test cleanser. There was no significant difference in skin surface pH between the two cleansers. Moreover, the increase in S. aureus was significantly correlated to the worsening of skin dryness and scaling. Conclusion These results suggest that not only antimicrobial activity but also the mildness, which minimizes cutaneous effects, are important for hand cleansers to prevent the growth of S. aureus. The cleanser formulated with AES, AEC and AG containing IPMP is mild and is effective to promote hand hygiene.

Femoral vein compression by a cyst is a rare feature. The most frequent aetiology is a synovial cyst of the hip joint. Adventitial cyst of the femoral vein is a much more infrequent cause. Morphological examination (Doppler US, CT scan or MRI) can easily recognise the cystic nature of the lesion but differentiation between these two causes can be difficult to make. In case of a synovial cyst, a plane of dissection can be found between the cyst and the femoral vein. This plane does not exist in case of adventitial cyst. The histological examination is identical because both cyst formations have the same tissue origin. We report four cases of femoral vein compression caused by a cystic lesions treated at our institution.

A magnetically levitated superconducting coil device, Mini-RT, has been constructed using a high-temperature superconductor for the purpose of examining a new magnetic confinement scheme of high-beta plasmas. The floating coil is wound with Bi-2223 Ag-sheathed tapes, and it is operated in the temperature range 20-40 K. The excitation tests of the coil were carried out and the rated current was successfully achieved by overcoming many difficulties. The first magnetic levitation was realized for one hour and the plasma production was initiated.

Using the two-step metalorganic vapor phase epitaxial growth on ZrB2 substrate, we demonstrate violet and UV light-emitting diodes (LEDs). The violet LED shows extremely linear L–I characteristics and a sharp single spectrum with a peak wavelength of 410 nm. In the UV-LED on ZrB2, we confirmed that the vertical conduction through the ZrB2/AlGaN interface is superior to the conventional lateral conduction. The use of ZrB2 substrate is promising for UV light emitting devices with low operating voltage. (© 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)