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BackgroundIn genome-wide association studies (GWAS), the strong association of ABCG2 rs2231142 variant with hyperuricemia and gout was confirmed in Asian population. Additionally, the obesity, diet, lifestyle, genetics and underlying comorbidities are important risks factors predisposing to hyperuricemia and gout. The systematic reviews revealed a significant link between obesity, systemic comorbidities and hyperuricosuria for predisposition of kidney stones (nephrolithiasis). However, whether ABCG2 plays an important role in the phathogenesis of nephrolithiasis remain unclear. The interaction between genetic factors and other risk factors of nephrolithiasis is still elusive.ObjectivesIn this study, we want to explore the association between ABCG2 rs2231142 variant and the risk of nephrolithiasis in modern Taiwanese population, and clarify the role of uric acid in nephrolithiasis formation.MethodsThis retrospective case-control study was conducted using the Taiwan Biobank database. A total of 120,267 individuals of Taiwanese Han Chinese aged 30-70 years were enrolled in the study. The primary outcome was the incidence of self-reported nephrolithiasis. Odds ratio (OR) of incident nephrolithiasis was analyzed by multiple logistic regression models and the interaction between ABCG2 rs2231142 variants, serum uric acid level, on the nephrolithiasis was explored. The multifactorial confounding factors for prediction of nephrolithiasis were also re-examined in our study.ResultsFinally, we identified 8,410 participants with nephrolithiasis and the prevalence was 11.52% and 4.37% in men and women, respectively. Older age (OR=1.08, 95% CI: 1.02-1.03, ppppppp=0.002), and hyperuricemia (OR=1.06, 95% CI: 1.04-1.08, pppp=0.083). Participants with regular physical exercise is a protective factor from nephrolithiasis (OR=0.95, 95% CI:0.9-1.0, p=0.048).ConclusionOur study demonstrated the risk of nephrolithiasis is significant association with ABCG2 rs2231142 variants. This risk also increased with systemic comorbidities (hyperlipidemia, hypertension, diabetes mellitus, and hyperuricemia), and lifestyle (obesity, and smoking). Regular physical exercise is associated with protective factor for incident nephrolithiasis.Table 1.Adjusted Odds ratio of kidney stone.VariableOR95% CIp-valueAge, years1.03(1.02-1.03)Gender female1.00—— male2.21(2.08-2.36)ABCG2 rs2231142 GG1.00—— GT1.12(1.06-1.18) TT1.18(1.09-1.28)Hyperlipidemia No1.00—— Yes1.40(1.29-1.51)Hypertension No1.00—— Yes1.67(1.57-1.78)Diabetes No1.00—— Yes1.16(1.06-1.26)0.002Hyperuricemia >7.0 mg/dL No1.00—— Yes1.06(1.04-1.08)Smoking No1.00—— Yes1.15(1.09-1.22)Alcohol use No1.00—— Yes0.92(0.84-1.01)0.083Regular physical exercise No1.00—— Yes0.95(0.90-1.00)0.048Overweight, BMI ≥24 kg/m2 No1.00—— Yes1.22(1.15-1.28)OR was adjusted for all variables in table.Disclosure of InterestsNone declared

BackgroundDespite recent advances of direct-antiviral agents (DAA) for Hepatitis C virus (HCV), it is still a prevalent worldwide issue and therapeutic challenge in patients with rheumatoid arthritis (RA). HCV viral replication may respond differently to biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) of different mechanism of action. Exosomal microRNA 155 (exo-miR-155) and exo-miR-122 have been implicated in modulating the host immune response and transmit anti-HCV factors to HCV-infected hepatocytes in patients with RA. However, it remains unknown how exosomal miRNAs may respond following bDMARDs and tsDMARDs treatment in HCV-infected patients with RA.ObjectivesWe aimed to study the changes of exo-miR-155 and exo-miR-122 following bDMARDs and tsDMARDs treatment in HCV-infected RA patients.MethodsWe prospectively enrolled RA patients taking anti-tumor necrosis factor-α (TNF-α) inhibitors, rituximab and tofacitinib. The effect of bDMARDs and tsDMARDs on HCV viral replication were assessed using an HCV-tricistronic replicon cell system. Exo-miR-155 and 122 were detected by quantitative PCR.ResultsHCV RNA replication in hepatocytes were not affected by tofacitinib treatment. Exo-miR-155 and exo-miR-122 were significantly increased in RA patients with HCV infection compared with those without HCV infection. We observed a dramatically increase of exo-miR-122 and decreased of exo-miR-155 in patients taking rituximab compared with the TNF-α inhibitors, tofacitinib and conventional synthetic DMARD groups. Finally, a reduction of exo-miR-122 and increase of exo-miR-155 levels were detected following DAA therapy for HCV.ConclusionExo-miR-155 and exo-miR-122 were potential biomarkers for RA patients with HCV infection. Further studies are needed to confirm our findings.References[1]Liao TL, Hsieh SL, Chen YM, Chen HH, Liu HJ, Lee HC, Chen DY (2018) Rituximab may cause increased hepatitis C virus viremia in rheumatoid arthritis patients through declining exosomal microRNA-155. Arthritis Rheumatol 70: 1209-1219.Table 1.Demographics of HCV-infected RA patients with bDMARDs and tsDMARDsanti-TNF-α therapy n=3Rituximab n=3Tofacitinib n=3Age62.8 (54.0-71.4)59.9 (49.9-67.6)63.8 (55.5-70.9)Gender (female, %)2 (66.7)3 (100)2 (66.7)Disease duration (years)11.0 (8.8-14.0)11.3 (7.6-17.0)12.0 (8.2-13.8)RF (IU/ml)155.0 (102.2-324.4)363.5 (265.0-538.7)95.0 (75.4-152.6)Anti-CCP antibody (units)132.7 (83.0-210.8)160.7 (106.9-400.3)112.0 (88.0-211.8)DAS285.3 (4.9-6.5)5.3 (4.8-6.4)5.2 (4.7-6.5)Figure 1.Comparison of exo-miR-122 (left panel) and exo-miR-155 levels (right panel) in RA patients receiving different biologics. All experiments were performed in triplicate and data are presented as the mean ± SD. RTX, rituximab; TNFi: tumor necrosis factor inhibitor; Tofa, tofacitinib. **pDisclosure of InterestsNone declared

BackgroundAzathioprine(AZA) is widely used in patients with autoimmun diseases. Thiopurine methyltransferase (TPMT) is the rate-limiting enzyme in AZA metabolization. Although several studies have investigated the association between TPMT polymorphisms and AZA-induced bone marrow suppression, the relationship of TPMT genotypes and hepatoxicity in patients taking AZA remained unclear.ObjectivesThis study aimed to investigate the correlation between TPMT polymorphisms and adverse reactions of AZA.MethodsThis retrospective case-control study enrolled patients with prior exposure to AZA at the Taichung Veterans General Hospital (TCVGH) using data extracted from the Taiwan Precision Medicine Initiative (TPMI) cohort. Drug-prescription profile, comorbidities, the occurence of leukopenia and hepatotoxicity following AZA treatment were extracted from hospital health records. Genetic variatns affecting TPMT activity were determined using SNP array. Participants were categorized into normal metabolizer (NM) and non-normal metabolizer (Non-NM) groups accordingly.ResultsFrom the 43,035 patients in the TCVGH-TPMI cohort, we identified 2,128 azathioprine users; 2.6% (57 out of 2,128) were classified as TPMT Non-NM group. After matching by age and sex, we included 50 TPMT Non-NM, including 1 poor metabolizers (PMs), 49 intermediate metabolizers (IMs), and 1,000 NM patients for further analysis. The Non-NM genotype was associated with hepatotoxicity compared with NM genotype (HR: 3.85, 95% CI: 1.83–8.10) after adjustment for gender, AZA dosage, and comorbidities(Table 1). In the Non-NM group, the 3-year cumulative incidence of hepatotoxicity was 6.6% for one year, 16.9% for two and three years, respectively, which was significantly higher than the NM group (p=0.003)(Figure 1).Table 1.Cox regression analysis of risk factors for hepatotoxicity following AZA treatmentHepatotoxicity*p valueHR95% CIAge0.990.981.010.60Male gender1.771.072.910.03TPMT non-NM genotype3.851.838.100.0004AZA dose (mg)1.001.001.010.31MedicationMTX1.621.032.570.04ComorbidityHepatitis B carrier1.180.403.480.76By Cox regression model with adjustment of all listed variables.*Development of GPT ≥ 150 U/L after AZA treatment; GPT, glutamic pyruvic Transaminase; TPMT, thiopurine S-methyltransferase; NM, normal metabolizer; AZA, azathioprine; MTX, Methotrexate; CI: confidence intervalFigure 1.Cumulative incidence of hepatotoxicityConclusionTPMT Non-NM genotype were associated with the developement of hepatotoxicity following AZA therapy. Prospective studies are needed to varify our results.References[1]Liu, Y.P., et al., Association between thiopurine S-methyltransferase polymorphisms and thiopurine-induced adverse drug reactions in patients with inflammatory bowel disease: a meta-analysis. PLoS One, 2015. 10(3): p. e0121745.Disclosure of InterestsNone declared

BackgroundSeveral studies have demonstrated immunogenicity after COVID-19 vaccination in patients with autoimmune rheumatic diseases (AIRD) [1], but the differences between mRNA-based and vector vaccines and the cellular responses to COVID-19 vaccines according to distinct immunogenicity in AIRD patients are still unclear.ObjectivesTo investigate the differences in efficacy and safety between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna) in patients with AIRD, and to explore the cell-cell interactions between high and low anti-SARS-CoV-2 IgG levels in patients with rheumatic arthritis (RA) by single-cell RNA sequencing (scRNA-seq).MethodsFrom September 16 to November 15, 2021, we consecutively enrolled 243 participants aged ≥20 years with AIRD who received COVID-19 vaccination, of whom 113 were immunized with AZD1222 and 130 with mRNA-1273. The level of serum IgG antibodies to the SARS-CoV-2 receptor-binding domain on the spike protein S1 subunit was quantified by electrochemiluminescence immunoassay at 4-6 weeks after vaccination. Moreover, peripheral blood mononuclear cells were isolated from two RA patient with high anti-SARS-CoV-2 IgG level and four RA patients with low level for scRNA-seq and cell-cell communication signal was analyzed by CellChat.ResultsThe anti-SARS-CoV-2 IgG seropositivity rate was 78.8% (89/113) for AZD1222 and 83.1% (108/130) for mRNA-1273. The level of anti-SARS-CoV-2 IgG was higher in patients who received mRNA-1273 than in those who received AZD1222 (β: 30.15, 95% CI: 11.67-48.63, p=0.002) (Table 1). Prednisolone-equivalent dose >5 mg/day and methotrexate (MTX) use in AIRD patients, and non-anti-tumor necrosis factor (TNF)-α biologics and Janus kinase (JAK) inhibitor use in RA patients were associated with inferior immunogenicity. ScRNA-seq revealed CD16-monocytes were predominant in RA patients with high anti-SARS-CoV2-IgG antibody level, and enriched pathways related to antigen presentation via major histocompatibility complex class II (MHC class II) were found (Figure 1). HLA-DRA and CD4 interaction was vigorous among all identified MHC-II pathway and was enhanced in high anti-SARS-CoV2-IgG antibody group.Table 1.Multivariate analysis of anti-SARS-CoV-2 IgG level in patients with rheumatic diseases following COVID-19 vaccinesMultivariate analysisβ95% CIp valueMedicationsGlucocorticoidsNot usedReference≤5 mg/day−22.48(−56.33,11.37)0.192>5 mg/day−23.45(−43.54,-3.36)0.022Methotrexate−24.89(−45.70,-4.08)0.019Targeted therapiesTargeted therapies group Not usedReference TNF inhibitor−15.78(−41.33,9.76)0.224 Non-TNF bDMARD−25.27(−55.47,4.93)0.100 JAK inhibitor−17.08(−47.23,13.07)0.265VaccineChAdOx1 nCoV-19/AZD1222ReferencemRNA-127330.15(11.67,48.63)0.002TNF: tumor necrosis factor, bDMARDs: biologic disease-modifying antirheumatic drugs, JAK: Janus kinase.Figure 1.The comprehensive cell atlas of PBMC of RA patients with high and low anti-SARS-CoV2-IgG antibodies. A) UMAP visualization of PBMC cells from RA patients. B) The proportion of cell types between high and low antibody groups. C) Volcano plot of CD16-monocyte showed differential expressed genes. D) Pathway analysis between high and low antibody groups; PRBC: peripheral blood mononuclear cell, RA: rheumatoid arthritis, NK cell: natural killer cell, pDC: plasmacytoid dendritic cell, CLP: common lymphoid progenitor.ConclusionmRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity in patients with AIRD. Enriched pathways related to antigen presentation via MHC class II in CD16-monocytes might be associated with higher anti-SARS-CoV2-IgG level in RA patients and further study is warranted.References[1]Geisen UM, Berner DK, Tran F, et al. Immunogenicity and safety of anti-SARS-CoV-2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort. Ann Rheum Dis. 2021;80:1306-1311.AcknowledgementsThe authors thank the Biostatistics Task Force of Taichung Veterans General Hospital for their assistance with the statistical analysis in this study.Disclosure of InterestsNone declared

BackgroundSystemic lupus erythematosus (SLE) is a chronic, autoimmune disease of an unknown etiology with a broad spectrum of organ manifestations, and patients with SLE have limited treatment options to NSAIDS, glucocorticoids, hydroxychloroquine and immunosuppressants. There is a lack of real-world evidence related to treatment patterns of SLE patients in Taiwan.ObjectivesTo describe the real-world patient demographics, clinical characteristics, and treatment patterns of patients with SLE in Taiwan.MethodsA retrospective observational study using Taiwan’s National Health Insurance Research Database (NHIRD) from 1/1/2014 to 12/31/2019 was undertaken. Patients holding catastrophic illness certificates for SLE in 2015-2017 were identified. Enrolled patients aged ≥ 18 years were then divided into three groups (mild, moderate, and severe) based on the highest severity patients experienced in the one year following the enrollment date using a published claims-based algorithm (Garris et al 2013) that incorporates the Systemic Lupus Erythematosus Disease Activity Index, Systemic Lupus Activity Measure, British Isles Lupus Assessment Group Index and expert clinical opinion, and indexed upon the first date of entering the severity group. Baseline patient characteristics and treatment patterns during the follow-up period were measured. The types of treatment considered were NSAIDs, glucocorticoids, hydroxychloroquine and immunosuppressants.ResultsA total of 20,181 patients with catastrophic illness certificates for SLE were included in this study. The mean age of all SLE patients was 46.5 years and patients were mostly female (89.1%). The mean Charlson Comorbidity Index (CCI) score of all SLE patients was 1.5 (SD 1.3). Of these patients, 29.3% (n=5,918) had mild SLE activity, 60.7% (n=12,253) moderate and 10.0% (n=2,010) severe. During the one-year follow-up period, moderate to severe patients had numerically higher utilization rate of all types of treatment compared with mild patients (Table 1). Of all oral glucocorticoid users,27.8% of severe patients used high-dose glucocorticoids (> 15 mg/day) compared to Table 1.SLE treatment utilization during the 1-year follow-up periodTotal (n=20,181)`Mild (n=5,918)Moderate (n=12,253)Severe (n=2,010)n%n%n%n%NSAID7,21235.71,40523.74,98340.782441.0Glucocorticoid14,01969.52,01534.110,29784.01,70784.9Hydroxychloroquine13,27865.82,86748.58,97073.21,44171.7Immunosuppressant7,63037.800.06,31951.61,31165.2Methotrexate8984.500.07866.41125.6Azathioprine5,64228.000.04,84339.579939.8Leflunomide1320.700.01171.0150.8Cyclosporin8544.200.07155.81396.9Mycophenolate9594.800.07746.31859.2Cyclophosphamide7903.900.0170.177338.5ConclusionThe complexity and intensity of therapeutic approaches in SLE were associated with increased disease severity and patients were often resistant to treatment. These findings reflect the disease burden in SLE patients and suggest there is a substantial unmet need in the SLE treatment paradigm for moderate to severe SLE patients.References[1]Garris C, et al. J Med Econ. 2013;16:667–677.Disclosure of InterestsYu Sheng Chang: None declared, Wen-Nan Huang: None declared, Chao-Hsiun Tang: None declared, Khai Ng Shareholder of: I am a minor shareholder of Eli Lilly & Company, Employee of: I am an employee of Eli Lilly & Company, Po-Ya Chuang Consultant of: I am a paid consultant for Eli Lilly &Company, Wesley Furnback Consultant of: I am a paid consultant for Eli Lilly & Company, Bruce Wang Consultant of: I am a paid consultant for Eli Lilly & Company, Ching-Yun Wei Shareholder of: I am a minor shareholder of Eli Lilly & Company, Employee of: I am an employee of Eli Lilly & Company, Bradley Wang Shareholder of: I am a minor shareholder of Eli Lilly & Company, Employee of: I am an employee of Eli Lilly & Company, Tamas Treuer Shareholder of: I am a minor shareholder of Eli Lilly & Company, Employee of: I am an employee of Eli Lilly & Company

Supplemental Material for Combination immunosuppressant therapy and lupus nephritis outcome: a hospital-based study Y.M.C. and W.T.H. contributed equally to this work. by Y M Chen, W T Hung, Y W Liao, C Y Hsu, T Y Hsieh, H H Chen, C W Hsieh, C T Lin, K L Lai, K T Tang, C W Tseng, W N Huang and Y H Chen in Lupus

Background Baricitinib (BARI) is an oral selective Janus kinase (JAK 1/2)1 inhibitor approved in the EU, Japan, and other countries for treatment (tx) of moderately to severely active rheumatoid arthritis (RA) in adults. RA therapies may increase risk of tuberculosis (TB).2 The use of isoniazid (INH) plays a vital role to control TB. However, INH may result in hepatic adverse events (AEs)3. Limited data exist on hepatic safety in TB patients (pts) with RA treated with JAK inhibitors and INH. Objectives To evaluate the hepatic safety in pts with RA, who were receiving INH for latent TB (LTBI) in BARI phase 3 trials. Methods This is a descriptive post-hoc analysis of three phase 3 studies: RA-BEAM, RA-BUILD, and RA-BEACON. All pts were screened for LTBI prior to randomisation. Pts with untreated LTBI and without documentation of prior completed tx, received INH at least for 4 weeks (wk) prior to randomisation and during the clinical trial period. Changes in ALT levels (≥1X,≥3X,≥5X, and ≥10X of ULN) from baseline up to 24 wk were analysed by tx groups (BARI 4 mg, BARI 2 mg, adalimumab [ADA], and placebo [PBO]). Results In total, 2516 pts were included in this analysis. Of these, 891 pts were treated with BARI 4 mg, 403 with BARI 2 mg, 330 with ADA, and 892 with PBO. Background csDMARDs, mainly methotrexate (MTX) were continued. Overall, 246 pts reported LTBI at screening across all tx groups. Of these, 169 with confirmed lab data received INH as LTBI tx. At wk 24, ALT≥1X was reported in 24 (41.4%) pts receiving BARI 4-mg+INH. None of the pts in BARI 4-mg+INH reported ALT level of ≥3X,≥5X, and ≥10X ULN. For BARI 2-mg+INH, ALT≥1X reported in 9 (33.3%) pts, ALT≥3X in 2 (7.4%), ALT≥5X in 1 (3.7%), and ALT≥10X in 1 (3.7%) of the pts. Among pts treated with ADA +INH, ALT≥1X was reported in 12 (44.4%), ALT≥3X in 2 (7.4%), ALT≥5X in 1 (3.7%), and ALT≥10X in none of pts. Among pts treated with PBO+INH, ALT≥1X was reported in 21 (36.8%), ALT≥3X and ALT≥5X levels were reported in 2 (3.5%, for both) of the pts. None of the pts reported ALT≥10X. One pt receiving INH in RA-BEAM PBO arm had temporary interruption of tx due to abnormal hepatic lab results. No study tx interruption or discontinuation was reported in INH users in BARI or ADA groups due to abnormal hepatic lab results. Conclusions The percentage of pts with ≥1X ULN ALT was numerically higher in INH group vs no INH and was consistent across PBO, BARI and ADA tx groups. The data do not suggest an increased hepatic safety risk in pts treated with BARI who were receiving concomitant INH. References [1] Dougados M, et al. Ann Rheum Dis. Jan 2017;76(1):88–95. [2] Lim CH, et al. PLoS One. 2017;12(6):e0178035. [3] Vanhoof J, et al. Ann Rheum Dis. Dec 2003;62(12):1241–1242. Disclosure of Interest T.-Y. Hsieh: None declared, W.-N. Huang: None declared, H.-P. Tony Consultant for: Abbvie, AstraZeneca, Chugai, Janssen Cilag, Eli Lilly and Company, Novartis, Roche, Sandoz Hexal, A. Balsa Grant/research support from: Pfizer, AbbVie, UCB, Roche, Novartis, Consultant for: Pfizer, Novartis, AbbVie, MSD, UCB, Roche, BMS, Novartis, Celltrion, Nordic, K. Winthrop Grant/research support from: Pfizer, BMS, Consultant for: Pfizer, UCB, Abbvie, Eli Lilly and Company, Amgen, BMS, M. Harigai Grant/research support from: BristolMyers Squibb K.K., Eisai Co., Ltd., Ono Pharmaceuticals, and Takeda Pharmaceutical Co., Ltd., Consultant for: Eli Lilly and Company, C. Dickson Employee of: Eli Lilly and Company, W.-S. Wu Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, I. de la Torre Employee of: Eli Lilly and Company, R. Liao Employee of: Eli Lilly and Company, L. Chen Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, S. Kumar Employee of: Eli Lilly and Company, B. Combe Grant/research support from: Pfizer, UCB, Consultant for: Abbvie, BMS, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Speakers bureau: BMS, Janssen, Lilly, MSD, Pfizer, Roche-Chugai, UCB

Summary The aim of this study was to investigate the normal high-resolution manometry and impedance (HRiM) values in the supine and sitting positions in the population of Northern China, and to investigate the influence of different body positions and bolus consistency on esophageal HRiM findings. In this study, healthy volunteers in the supine position underwent esophageal HRiM examination of 10 swallows of 5 mL normal saline solution and 10 swallows of 5 mL synthetic gel of known viscosity, and in the sitting position of an additional five swallows of a synthetic gel of known viscosity. Total bolus transit time (TBTT), complete bolus transit rate (CBTR), distal contractile integral (DCI), distal esophageal amplitude (DEA), and integrated relaxation pressure (IRP) were measured. Sixty-two healthy volunteers were examined in the supine position and 45 of these performed additional swallows of the viscous gel in the sitting position. In the supine position, normal values for swallowing the liquid and viscous boli were as follows: TBTT 6.9 ± 0.9 and 8.0 ± 1.2 s (P < 0.001), CBTR 90.3 ± 14.0 and 77.9 ± 20.3% (P < 0.001), DCI 1891.5 ± 1131.9 and 1967.8 ± 1140.1 mmHg.s.cm (P = 0.227), DEA 95.3 ± 35.4 and 98.7 ± 37.5 mmHg (P = 0.148), and IRP 10.4 ± 4.9 and 9.0 ± 4.2 mmHg (P < 0.001), respectively. For swallows of the viscous boli in the sitting position, TBTT, DCI, DEA, and IRP were significantly decreased, while CBTR was unchanged (P = 0.075). Normal HRiM values of the population of Northern China were established. Esophageal transit times of viscous boli were significantly slower, more often incomplete and produced less normal peristalsis in the supine position than swallows of liquid boli. Independent reference values for different manometric systems, body positions, and population need to be established before clinical application.

The aim of this study was to investigate the normal high-resolution manometry and impedance (HRiM) values in the supine and sitting positions in the population of Northern China, and to investigate the influence of different body positions and bolus consistency on esophageal HRiM findings. In this study, healthy volunteers in the supine position underwent esophageal HRiM examination of 10 swallows of 5 mL normal saline solution and 10 swallows of 5 mL synthetic gel of known viscosity, and in the sitting position of an additional five swallows of a synthetic gel of known viscosity. Total bolus transit time (TBTT), complete bolus transit rate (CBTR), distal contractile integral (DCI), distal esophageal amplitude (DEA), and integrated relaxation pressure (IRP) were measured. Sixty-two healthy volunteers were examined in the supine position and 45 of these performed additional swallows of the viscous gel in the sitting position. In the supine position, normal values for swallowing the liquid and viscous boli were as follows: TBTT 6.9 ± 0.9 and 8.0 ± 1.2 s (P0.001), CBTR 90.3 ± 14.0 and 77.9 ± 20.3% (P0.001), DCI 1891.5 ± 1131.9 and 1967.8 ± 1140.1 mmHg.s.cm (P = 0.227), DEA 95.3 ± 35.4 and 98.7 ± 37.5 mmHg (P = 0.148), and IRP 10.4 ± 4.9 and 9.0 ± 4.2 mmHg (P0.001), respectively. For swallows of the viscous boli in the sitting position, TBTT, DCI, DEA, and IRP were significantly decreased, while CBTR was unchanged (P = 0.075). Normal HRiM values of the population of Northern China were established. Esophageal transit times of viscous boli were significantly slower, more often incomplete and produced less normal peristalsis in the supine position than swallows of liquid boli. Independent reference values for different manometric systems, body positions, and population need to be established before clinical application.

TiO2 nanotubes promoted with Pt metal were prepared and tested to be the photocatalytic dehydrogenation catalyst in neat ethanol for producing H2 gas (C2H5OH→→→C3CHO +H2). It was found that the ability to produce H2, the liquid phase product distribution and the catlyst stability of these promoted nano catalysts all depended on the Pt loading and catalyst preparation procedure. These Pt/TiO2 catalysts with TiO2 nanotubes washed with diluted H2SO4 solution produced 1, 2-diethoxy ethane (acetal) as the major liquid phase product, while over those washed with diluted HCl solution or H2O, acetaldehyde was the major liquid phase product.

Fractionation and reconstitution studies of a flour from 1B/1R wheat showed that the factor causing sticky dough was water soluble. In addition, these studies showed that enzymes and lipids in the flour were not responsible for producing sticky dough. Dialysis experiments showed that the active component was nondialyzable. Gel-filtration chromatography of the retentate fraction showed that the substance causing sticky dough contained both a carbohydrate and a UV-absorbing material. Treatment of the active fraction with base caused the fraction to lose its ability to cause stickiness. The UV-absorbing material and the carbohydrate fraction had to be covalently linked for the compound to be active. Gas chromatography-mass spectrometry and HPLC analysis showed that the UV-absorbing moiety was predominantly trans-ferulic acid, and the carbohydrate part was a glucose polymer. The glucose polymer was not degraded by α-amylase but was degraded by lichenase, suggesting that the glucose polymer was a mixe...

A LED was fabricated by first forming a porous region on a cast polycrystalline silicon substrate by anodization and then depositing a Au layer. Under forward bias, the LED was observed to have a stable yellowish white emission. Based on the measured spectra, it is proposed that the origin of the emission is due to microplasma formed in the depletion region of the heterojunction formed between the porous polysilicon layer and the polysilicon bulk. The results suggested that the cast polycrystalline substrate can be used for cheap and largearea applications in porous silicon devices.

We have investigated the materials and photoluminescence properties of porous polysilicon films formed by chemical etching. The polysilicon samples were prepared by furnace crystallization of r.f. sputtered silicon films on a crystalline silicon substrate. The materials properties were observed by SEM, TEM, XRD and FTIR. XRD showed that the grains with (111) orientation have the highest etching rate and are probably most efficient in forming porous regions. The photoluminescence intensity depends on the annealing temperature of the sputtered Si film, and has a maximum value at a temperature around . This temperature dependence can be explained from the relative peak intensities of grains of different orientation measured by XRD. Rapid thermal oxidation of porous polysilicon films was found to degrade the photoluminescence intensity.

Although lipoprotein modification has been implicated in atherogenesis, the effect of modified forms of lipoproteins on vascular cell function has not been fully resolved. We have investigated lipoprotein-induced prostaglandin production by macrovascular endothelial cells. This study delineates early responses of endothelial cells after exposure to native and modified forms of the lipoproteins. Modification of lipoproteins by oxidation or glycation significantly affected the capacity of lipoproteins to induce prostacyclin (PGI2) production by bovine aortic endothelial cells (BAEC). Modified low-density lipoprotein (LDL) increased PGI2 production in the short term (up to 24 h), but oxidized LDL caused an inhibition of PGI2-producing capacity in longer term incubations (48-72 h). Glycated (Glc) high-density lipoprotein 3 (HDL3) caused higher production of PGI2 in the short term (4-24 h) but reached similar levels as HDL3 over time. Glycation of high-density lipoprotein 2 had no effect on the PGI2-producing capacity of the lipoprotein. Thus modification of the lipoproteins affects their potential to induce PGI2 production in endothelial cells, and this may have an influence on vascular function in disease states such as diabetes and atherosclerosis. Although the changes appear to contradict data from long-term in vivo studies, these results from in vitro studies may reflect the situation in very early lesion development. GlcLDL, while causing an increase in endothelial cell PGI2 production, may be involved in compromised endothelial function, since GlcLDL is prone to oxidation.

A series of single-phase compounds with tetragonal triple-perovskite structure is studied by Rietveld analysis. For , all of the ions enter the centre site: the site of the tetragonal phase. For , a maximum of about 1/2 of the sites are occupied by ions and the extra ions enter the site. Double plateaux are found between and (the difference between the occupancy factor of ions at the site and that of ions at the site). It is suggested that of the La - Ca - Ba - Cu - O compounds containing 50 mol% copper atoms with tetragonal triple-perovskite structure can be predicted from the correlation of versus .

We calculate the effects of weak disorder on a strongly correlated electron system, namely a version of the infinite-U Hubbard model with general charge for which a 1/N expansion can be carried out (N being the orbital degeneracy). The partition function and quasiparticle decay rate are calculated to next leading order in the 1/N expansion by summing all ladder type diffusive corrections in the impurity potential. We find that away from the critical metal-insulator filling these quantities exhibit the power law behaviour expected on the basis of general weak-interacting theories. Very close to the metal-insulator filling, however, the situation changes and new, sublinear power law components are obtained. These new power laws are a result of the diffusion pole crossing over to a q4 behaviour, which is in turn a consequence of the 'holon' like propagation of the charge fluctuations in the pure system.

Dipalmitoylphosphatidylcholine lipid molecules adsorbed on a silver electrode were found to exhibit a conformational phase transition when investigated by means of surface-enhanced Raman scattering. The observed order-to-disorder transition of the hydrocarbon chain is voltage dependent and exhibits hysteresis phenomena. It is suggested that the adsorption of lipid molecules occurs at the phosphocholine moiety and the kinetic process for the transition involves a voltage-induced conformational change of the head group.

The electrical transport properties of CoSi2 and Co(SixGe1−x)2 thin films formed by solid state interaction and co‐evaporation in the range of 4–300 K were studied. The Hall effect data indicate a hole carrier conduction in all samples. The rapid thermal annealed CoSi2 exhibits a typical metallic conduction with a residual resistivity of 3.3‐μΩ‐cm and room‐temperature (RT) resistivity of 15 μΩ cm. The co‐evaporated CoSi2 and Co(Si0.9Ge0.1)2 films after low temperature annealing up to 250 °C show a low resistivity of 70–80 μΩ cm at RT and change little down to 4 K. The hole carrier density of all the samples studied has values close to 2–3×1022 cm−3, while the carrier Hall mobility has large differences.

Background: It is important for older adults to maintain independence in activities of daily living (ADL) to have optimal quality of life. Many factors including the biological, psychological, and social factors have been linked to disability in basic ADL (BADL). Previous studies have investigated the relationship between BADL dependence and functions in older adults. However, the relationship between BADL difficulty and functions has not been well examined. Selfreported BADL difficulty reflects an individual’s awareness, and may serve the researcher better when the interest is about the disease consequences and the objective is to evaluate intervention effectiveness. Purpose:Unlikemuchof the previous research examining the BADL dependence, the purpose of the study is to investigate the relationship between BADL difficulty and cognitive and physical functions in community-dwelling older adults. Self-reported difficulty is believed to precede dependence. Identifying older adults with BADL difficulties may help clinicians to detect early functional decline. Methods: In the cross-sectional study, a convenience sample of 51 community-dwelling older adults was recruited. Interviews were conducted to collect data on self-reported difficulty in six BADLs (bathing, dressing, eating, transfer: getting in/out of bed/chairs, walking, using toilet), clock drawing tests (CLOX1&CLOX2),Mini-Mental State Exam (MMSE), and 5 physical function tests including Short Physical Performance Battery (SPPB), Berg Balance Scale (BBS), gait speed, 5 times sit-to-stand test, and Timed Up & Go Test (TUG). For each BADL task, the student’s t test and Mann–Whitney testwere use to compare differences between older adults with and without difficulty. Results: Among the six BADLs, walking, toileting and transfer are associated with poor cognitive or lower extremity physical functions. Compared to older adults who reported walking difficulty (n= 8, CLOX1= 5.71 ± 4.31, CLOX2 = 8.71 ± 2.29, BBS = 40.38 ± 7.27, SPPB = 4.25 ± 2.49, gait speed = 0.41 ± 0.15 m/sec, TUG = 26.16 ± 6.69 sec), older adults without walking difficulty performed better in cognitive and physical function tests (n = 43, CLOX1 = 9.80 ± 3.31, CLOX2 = 11.64± 2.53, BBS = 49.24± 7.03, SPPB = 7.45± 2.46, gait speed = 0.73± 0.28 m/sec, TUG = 15.90 ± 6.12 sec). Difficulty in toileting is associated with lower SPPB score (2.50 ± 0.71) and longer TUG time (30.27 ± 4.59 sec) (p < .05). Difficulty in transfer is associated with lowerMMSE (17.00± 0.00) andCLOX2 score (5.00± 0.00) (p< .05). Conclusion(s): In older adults, difficulty in walking and toileting is associated with poor lower extremity physical function. Difficulty in walking and transfer is associated with lower cognitive function. Implications: Self-reported difficulty in BADL, such as walking,may suggest the need for further cognitive and physical function screening. Screening older adults with BADL difficulty would allow clinicians to identify high-risk individuals and provide early interventions to prevent or delay onset of future BADL dependence.

To measure the voice samples of the normal aged in order to systemically study the features of the voice changes.To collect and analyze 146 voice samples of the normal aged with sonogram.The fundamental frequency of the voice of the aged decreases and rises in the male more than 80 years older. The low frequency harmonics are regulation and the intensity is strong in the formant of the aged. The difference reduces in voice between male and female. The harmonics to noise ratio tends downwards and the amplitude perturbation quotient tends upwards along with the growth of age in the aged male. The changes of the above-mentioned parameters are not significant in the aged female.The voice changes are normal physiological ones in the normal aged. The changes of the parameters are used to evaluate normal aged voice and abnormal one. The changes show that the function in the aged phonation tends to decline to a certain extent and it must be protected and be trained.

This research project examined the feasibility of a second generation high-temperature coal gas desulfurization process in which elemental sulfur is produced directly during the sorbent regeneration phase. Two concepts were evaluated experimentally. In the first, FeS was regenerated in a H2O-O2 mixture. Large fractions of the sulfur were liberated in elemental form when the H2O-O2 ratio was large. However, the mole percent of elemental sulfur in the product was always quite small (<

Previous studies on electroluminescence in porous silicon were based on crystalline wafers. In this paper, we shall report the characteristics of a LED based on porous effects in a cast polycrystalline silicon substrate. A layer of porous region was first formed on a cast polycrystalline silicon substrate by anodization, followed by the deposition of a semitransparent Au layer. Under forward bias, the LED emits stable yellowish white light (with the presence of bright spots) for currents above 20 mA/cm2. From the electroluminescence spectra measured, we suggest that the emission is due to the recombination of electron-hole pairs in a microplasma region. We propose a model where the microplasma is present in the depletion region of the heterojunction formed between the bulk polysilicon and the surface porous polysilicon. The defects and grain boundaries in a polycrystalline material facilitate the formation of such microplasma. The heterojunction model will also be used to explain the current characteristics of the LED. The effect on the LED characteristics due to indium coating on the porous substrate prior to Au deposition was studied, and the results agree with the heterojunction model. Our work shows that cast polycrystalline silicon substrates have potential for LED fabrication in cheap and large area applications.

Background Systemic lupus erythematosus (SLE) is an autoimmune disease with a wide range of clinical manifestations and most cases of SLE occur in women. There is strong evidence on the relationship between physical activity and the primary prevention of chronic health problems in women. The metabolic syndrome is defined by a clustering of atherosclerotic cardiovascular disease risk factors, characterized by central obesity, glucose intolerance, hypertension, dyslipidemia, insulin resistance (IR) and a systemic proinflammatory and procoagulating state. Objectives The aim of this study was to investigate the impact of metabolic syndrome and physical activity in clinically quiescent SLE patients, especially emphasis on the interaction of IR, bone metabolism, and inflammation. Methods Seventy five female clinically quiescent SLE patients attending outpatient clinics at Taichung Veterans General Hospital were enrolled in this study. Thirty age-matched healthy females from the local community served as controls. Metabolic syndrome was based on the National Cholesterol Education Program (NCEP/ATP III) definition. The homeostasis model assessment (HOMA) was used to evaluate the status of IR. Estimates of energy expenditures represented by total activity calorie, physical activity calorie, total activity calorie per body weight, and physical activity calorie per body weight of studied patients were assessed using the RT3 tri-axial accelerometer in a seven-day period. Bone mineral density (BMD) and body composition were measured by dual energy X-ray absorptiometry. Electrochemiluminescence immunoassay was performed to measure bone metabolism markers including C-terminal crosslinking telopeptide of type I collagen, parathyroid hormone, type I procollagen N-terminal propeptide, and osteocalcin. Serum levels of inflammatory markers were assessed using the Bio-Plex Human Cytokine 17-Plex panel in combination with the Bio-Plex Suspension Array System. Results All of the patients were non-smokers and performed regular daily activities. The high prevalence of metabolic syndrome was present in this study. About 36% of studied patients were considered IR with a value of HOMA IR greater than 2.0. Incidence rate was also significantly higher in SLE patients with IR than SLE patients without IR. SLE patients with IR tended to have higher estimates of energy expenditure compared to those in SLE patients without IR. However, there was no statistically significant difference in physical activity between patients stratified by HOMA IR. About 53% of studied patients were considered osteopenia or osteoporosis. Osteopenia or osteoporosis was more prevalent in SLE patients with IR than SLE patients without IR. However, total BMD and the BMD at the spine and femoral neck were not significantly different between SLE patients with and without IR. SLE patients regardless of IR had significantly lower circulating levels of osteocalcin than healthy subjects. With respect to inflammation, SLE patients with IR had significantly higher serum levels of monocyte chemoatractant protein-1 and macrophage inflammatory protein-1β than healthy subjects. Conclusions Although SLE patients in this study were considered clinically quiescent, a possible link between insulin resistance, bone metabolism, and inflammation exists. Disclosure of Interest None Declared

The traffic of vehicles from downtown to suburban areas is investigated numerically. We propose a cellular automaton to simulate the traffic of vehicles within a city regulated by traffic lights. Both traffic flow and travel time are presented and we discuss some strategies to optimize these quantities.

The oxygen tension for half saturation (P50) was determined for venous blood in thirteen patients with the adult respiratory distress syndrome undergoing intensive therapy. The mean value for P50was found to be significantly lower than the value found in ten normal control subjects (22.9 mmHg and 26.7 mmHg respectively; t = 3.03, P < 0.01).The extent of reduction in P50was not related to serum phosphate level nor was it a predictor of short-term outcome. It is unlikely that the slight left-shifted oxygen-haemoglobin dissociation curve contributes in a major way to an oxygen delivery deficiency and its cause is unexplained.

The utilization and development of nitrogen-fixing trees as resources has played an important role in establishing forests in denuded land, in producing more wood in industrial plantations, in conserving soil and water, and in improving ecosystems. A survey on the nodulation status of some tropical and subtropical woody leguminous species in Fujian Province and an investigation of the ecophysiology of symbiotic nitrogen fixation in several leguminous trees have been carried out in recent years.

A l'ordre 1/N 2 , on trouve une contribution substantielle a l'amplitude de diffusion des paires de Cooper provenant de l'echange resonnant de deux modes a son nul. Cette contribution est repulsive et peut etre identifiee avec de fortes fluctuations de spin ferromagnetiques

Egg sphingomyelin vesicles were used to assay aggregation/fusion activities of proteins from Taiwan (Naja naja atra) venom to avoid the problem of phospholipase A2 contamination during protein purification. It led to the identification of a new cardiotoxin (CTX) analogue protein (CTX V) with major aggregation/fusion, but few hemolysis, activities. On the contrary, cardiotoxin (CTX III) induced significant hemolysis of human red blood cells but exhibited few aggregation/fusion activities. To study the structure/activity relationship of these CTX-induced processes, the amino acid sequence of CTX V was determined and its aggregation/fusion activity was compared with that of CTX III by transmission electron microscopy, quasielastic laser light scattering, differential scanning calorimetry, and fluorescence spectroscopy. The results show that the CTX-induced fusion process at temperatures slightly above that of the gel to liquid-crystalline phase transition of sphingomyelin vesicles can ultimately convert small sonicated vesicles into large fused vesicles with sizes of 1-2 microns. The abilities of CTX V to induce the leakage of sphingomyelin vesicles content and to cause the fusion of vesicles are approximately 10-fold higher than those of CTX III. Based on the CTX structures determined in the present and other studies, it is suggested that the amino acid residue X within the well conserved sequence of -Cys-Pro-X-Gly-Lys-Gln-Leu-Cys- plays a role in the interaction of CTX with lipid molecules. The lipid phase transition could further enhance the protein-lipid interaction in the process leading to the fusion of vesicles.

Thermoelectric power and thermal conductivity have been measured as a function of temperature on ceramic ${\mathrm{YBa}}_{2}$${\mathrm{Cu}}_{3}$${\mathrm{O}}_{7\mathrm{\ensuremath{-}}\mathrm{\ensuremath{\delta}}}$ exposed to fast-neutron fluences of up to 6\ifmmode\times\else\texttimes\fi{}${10}^{18}$ n${\mathrm{cm}}^{\mathrm{\ensuremath{-}}2}$. Irradiation causes large changes in the magnitude and temperature variation of the thermopower and, for the highest doses, results in a complete suppression of the peak in thermal conductivity that is characteristic of the nonirradiated 1:2:3 superconducting ceramics below ${T}_{c}$. The likely physical origin of the changes are the defects created in the structure by fast neutrons that drastically limit the mean-free path of phonons and the charge carriers.

It is assumed that the material of the beam is governed by a nonlinear Maxwell model. The temperature and imperfection density and consequently the two inelastic material parameters are taken as random functions of the distance along the neutral axis. A perturbation about the initial axial stress is employed, analogous to the approach used in Cozzarelli, Wu, and Tang [“Lateral Vibration of a Nonlinear Viscoelastic Beam under Initial Axial‐Tension,” J. Sound Vibration 13 (1970)]. As in Cozzarelli and Huang [Effect of Random Material Parameters on Nonlinear Steady Creep Solutions,” Int. J. Solids Structures 7 (1971)], the problem is separated into two uncoupled problems—a “random temperature problem” and a “random imperfection problem.” Two special cases are fully analyzed: (a) the random parameters are random processes that are only slightly raudom, and (b) the random parameters are random variables that are largely random. Statistical results are obtained for the lateral velocity, bending moment, logarith...