Gotowa bibliografia na temat „Corporation of Beccles Fen”

Abstract The aim of the study was to assess the concentration of selected trace elements in organic soils used as a source to obtain a unique peat extract for cosmetics production. Peat material for laboratory analysis were collected from fen peatland located in the Prosna River Valley (Borek village). Studied peatland is managed by “Torf Corporation” company as a source of material to obtain peat extract for cosmetics production. In the collected soil samples (four soil profiles) Zn, Cu and Pb concentrations were determined by using atomic absorption spectrometer SpectraAA 220 (Varian), after acid digestion. Obtained results showed that the highest concentrations of selected trace elements were recorded in the surface horizons of organic soils. This fact might be the results of Prosna river flooding or air deposition. Howevere, according to the new Polish regulations (Ordinance of the Minister for Environment 01.09.2016 - the way of conducting contamination assessment of the earth surface), the content of trace elements in the examined soils was greatly belowe the permissible limit for areas from group IV (mine lands). Thus, described soils are proper to obtain peat extract used as a component in cosmetic production.

Background:In the absence of evidence-based treatment guidelines, medication use in SLE is highly variable. Low rates of remission and lupus low disease activity state (LLDAS) suggest that suboptimal responses to standard medications, which include glucocorticoids (GC), anti-malarial (AM) drugs and immunosuppressive (IS) agents, are common. Understanding the utility of current medications will facilitate the selection of patients for advanced therapies as they emerge.Objectives:To examine medication use patterns in a large multicentre SLE cohort.Methods:We used 2013-18 data from the Asia Pacific Lupus Collaboration (APLC) cohort in which disease activity (SLEDAI-2K) and medication details were captured at every visit. LLDAS was defined as in Golderet al., 2019 (1). We examined the use of medication (med) categories (GC &/or AM &/or IS) by SLE disease activity and LLDAS at the visit level. Additionally, we performed Cox regression analyses to determine the time-to-discontinuation of meds stratified by SLE disease activity, ranked by time-adjusted mean SLEDAI-2K, and by percent-time spent in LLDAS.Results:We analysed data from 19,804 visits of 2,860 patients. We observed 8 med categories: no meds; GC, AM or IS only; GC+AM; GC+IS; AM+IS and GC+AM+IS (triple therapy). Triple therapy was the most frequent med pattern (32%); single agents were used in 21% of visits and biologicals in only 3%. Among visits where SLEDAI-2K was ≥10, triple therapy was used in 46%, with median [IQR] GC dose 10 [6, 24] mg/day; in contrast, among visits with SLEDAI-2K≤4 triple therapy was used in 28% (p<0.01). Patients in LLDAS received less combination therapy than those who were not in LLDAS.Med persistence (survival analysis) varied widely, with lowest survivals for IS. Patients with time-adjusted mean SLEDAI-2K ≥10 had lower discontinuation of GC and higher discontinuation of IS including azathioprine, leflunomide and cyclosporine (Table 1). In contrast, increased time in LLDAS was associated with reduced discontinuation of AM and azathioprine.GCAMISMPhMPhAAZAMTXCyALEFOverall med survival, days to 25% discontinuation (95%CI)1048(938, 1197)1267(1113, 1428)175(175, 182)387(252, 756)409(350, 476)525(219, 686)268(182, 350)329(190, 524)Univariable associations,HR (95% CI) p-valueDisease activity≤41.001.001.001.001.001.001.001.00>4 & <100.69 (0.56,0.84)p<0.0011.15 (0.92,1.44)0.20.92 (0.80,1.05)0.21.37 (0.78,2.42)0.31.16 (0.97,1.39)0.111.11 (0.72,1.71)0.61.26 (0.90,1.77) 0.181.88 (1.07,3.30) 0.03≥100.65 (0.35,1.21) 0.181.56 (0.94,2.59) 0.080.84 (0.45,1.57)0.61.92 (0.80,4.63)0.142.69 (1.86,3.91) p<0.0011.85 (0.92,3.71) 0.082.66 (1.36,5.21) 0.0041.62 (1.13,2.32)0.009LLDAS<50%1.001.001.001.001.001.001.001.00≥50%1.30 (1.09, 1.55)0.0030.67 (0.54, 0.84)<0.0011.22 (1.08, 1.40)0.0020.83 (0.44,1.57)0.60.83 (0.69, 1.00)0.0540.70 (0.46, 1.07)0.101.29 (0.92, 1.83)0.140.43 (1.5, 1.25)0.12Conclusion:In a large multicentre SLE cohort, most patients were receiving combination treatment. AM treatment survival was high and associated with low disease activity, GC survival was high and associated with high disease activity, while IS survival was low. Patients with high disease activity received more medication combinations but had reduced IS survival. These data suggest ongoing unmet need for improved medications for treatment of SLE.Reference:Golder, V., et al Lancet Rheum. 2019 1(2):e95-102Disclosure of Interests:Rangi Kandane-Rathnayake Grant/research support from: The APLC has received financial (non-restricted educational) grants from AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Janssen, EMD Serono, Eli Lilly and UCB for the LLDAS Validation Study., Worawit Louthrenoo: None declared, Shue Fen Luo: None declared, Yeong-Jian Wu Consultant of: Pfizer, Lilly, Novartis, Abbvie, Roche, Speakers bureau: Lilly, Novartis, Yi-Hsing Chen Grant/research support from: Taiwan Ministry of Science and Technology, Taiwan Department of Health, Taichung Veterans General Hospital, National Yang-Ming University, GSK, Pfizer, BMS., Consultant of: Pfizer, Novartis, Abbvie, Johnson & Johnson, BMS, Roche, Lilly, GSK, Astra& Zeneca, Sanofi, MSD, Guigai, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma, Thermo Fisher, Gilead., Paid instructor for: Pfizer, Novartis, Johnson & Johnson, Roche, Lilly, Astra& Zeneca, Sanofi, Astellas, Agnitio Science Technology, United Biopharma., Speakers bureau: Pfizer, Novartis, Abbvie, Johnson & Johnson, BMS, Roche, Lilly, GSK, Astra& Zeneca, Sanofi, MSD, Guigai, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma, Thermo Fisher, Gilead., Vera Golder: None declared, Aisha Lateef: None declared, Jiacai Cho: None declared, Sandra Navarra Speakers bureau: Astellas, Novartis, Pfizer, Johnson & Johnson, Abbvie, Leonid Zamora: None declared, Laniyati Hamijoyo Speakers bureau: Pfizer, Novartis, Tanabe, Abbot, Dexa Medica, Roche, Sargunan Sockalingam: None declared, Yuan An: None declared, Zhanguo Li: None declared, Yasuhiro Katsumata: None declared, masayoshi harigai Grant/research support from: AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., and Teijin Pharma Ltd. MH has received speaker’s fee from AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Oxford Immuotec, Pfizer Japan Inc., and Teijin Pharma Ltd. MH is a consultant for AbbVie, Boehringer-ingelheim, Kissei Pharmaceutical Co., Ltd. and Teijin Pharma., Yanjie Hao: None declared, Zhuoli Zhang: None declared, Madelynn Chan: None declared, Jun Kikuchi: None declared, Tsutomu Takeuchi Grant/research support from: Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corporation, Nippon Kayaku Co., Ltd, Takeda Pharmaceutical Company Ltd, UCB Pharma, Shionogi & Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co. Ltd., Consultant of: Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc., Eli Lilly Japan KK, Speakers bureau: AbbVie GK, Eisai Co., Ltd, Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co Ltd, Bristol-Myers Squibb Company, AYUMI Pharmaceutical Corp., Eisai Co., Ltd, Daiichi Sankyo Co., Ltd., Gilead Sciences, Inc., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Dainippon Sumitomo Co., Ltd., Fiona Goldblatt: None declared, Sean O’Neill: None declared, Chetan Karyekar Shareholder of: Johnson & Johnson, Consultant of: Janssen, Employee of: Janssen Global Services, LLC. Previously, Novartis, Bristol-Myers Squibb, and Abbott Labs., Jennifer H. Lofland Employee of: Janssen, Sang-Cheol Bae: None declared, Chak Sing Lau: None declared, Alberta Hoi: None declared, Mandana Nikpour: None declared, Eric F. Morand Grant/research support from: AstraZeneca, Consultant of: AstraZeneca, Speakers bureau: AstraZeneca

BackgroundThe lupus low disease activity state (LLDAS) treat-to-target definition sets a ceiling for acceptable disease and treatment burden in SLE. Definition of Remission in SLE (DORIS) is a more stringent state, but as it is concentric with LLDAS many patients in LLDAS also meet the DORIS remission definition. Studies in cohorts with a majority of patients in remission poorly separate LLDAS and remission, leading to debate about the independent effects of LLDAS on SLE outcomes.ObjectivesWe examined whether being in LLDAS but not remission provided protection against adverse outcomes of flare, irreversible organ damage accrual and mortality in patients with SLE.MethodsData from a 13-country longitudinal SLE cohort (ACR/SLICC criteria), collected prospectively between 2013 and 2020, were analysed. Organ damage and flare were captured using SLICC Damage Index and SELENA-SLEDAI Flare Index, respectively. LLDAS was defined as Golderet al., 2019 [1] (SLEDAI<4, no new activity, PGA<1, prednisolone (PNL)<7.5 mg/d, antimalarials (AM) and immunosuppressants (IS) allowed). Remission was defined as Vollenhovenet al, 2021 [2] (clinical SLEDAI=0, PGA <0.5, PNL<5 mg/d, AM/IS allowed).Results3,811 patients with ≥ 2 visits followed over a median of 2.8 years [IQR: 1.0 to 5.3] were studied. 80 (2.1%) patients died; 717 (21%) accrued organ damage, and 2,142 (56%) experienced mild-moderate or severe flare during the study period. 55% (n=2,099) attained LLDAS but not remission (LLDAS+REM-) at least once, with a median (IQR) cumulative percent-time spent in LLDAS+REM- of 21.5% [9.8, 42.9]. Overall, 63% attained both LLDAS and remission (LLDAS+REM+) with median (IQR) cumulative time 45% [22, 71]; 18% attained LLDAS+REM-., and 19% of patients never attained LLDAS or REM.Compared to patients who never attained LLDAS or remission (LLDAS-REM-), LLDAS+REM- attainment at any time during the study observation period provided significant protection against subsequent flare and damage accrual, and protection against mortality with borderline statistical significance, after adjusting for potential confounding factors (Table 1). Similarly, ≥50% of cumulative observed time in LLDAS+REM- provided significant protection against flare and damage accrual but not mortality, possibly due to lack of power (Table 1). Protective effects of LLDAS+REM+ were also confirmed.Table 1.Longitudinal associations of LLDAS+REM- attainment with flare, organ damage accrual and mortalityFlaretDamage accrualtMortalitytHR1(95%CI)p-valueHR2(95%CI)p-valueHR3(95%CI)p-valueNot in LLDAS or REMt-11.001.001.00LLDAS+REM-t-10.66 (0.60, 073)p<0.00010.63 (0.52, 0.77)p<0.00010.14 (0.02, 1.07)p=0.059LLDAS+REM+t-10.57 (0.52, 0.61)p<0.00010.46 (0.39, 0.54)p<0.00010.22 (0.08, 0.65)P=0.006<50%T in LLDAS+REM-t-11.001.001.00≥50%T in LLDAS+REM-t-10.71 (0.62, 0.81)p<0.00010.72 (0.56, 0.92)p=0.0100.39 (0.14, 1.10)p=0.08<50%T in LLDAS+REM+t-11.001.001.00≥50%T in LLDAS+REM+t-10.62 (0.56, 0.67)P<0.00010.64 (0.53, 0.76)P<0.00010.53 (0.19, 1.43)p=0.21Hazard ratios adjusted for1age and national gross domestic product (GDP);2age, GDP and baseline organ damage, and3GDP and SDI score. T=time.ConclusionAttainment of LLDAS provides significant protection against flare and organ damage accrual even when excluding patients who are also meet the definition of remission. LLDAS is an independent predictor of improved outcomes in SLE.References[1]Golder V, Kandane-Rathnayake R, Huq M, Nim H, Louthrenoo W, Luo SF, et al. Lupus low disease activity state as a treatment endpoint for systemic lupus erythematosus: a prospective validation study. The Lancet Rheumatology. 2019; 1(2):e95–e102.[2]van Vollenhoven RF, Bertsias G, Doria A, Isenberg D, Morand E, Petri MA, et al. 2021 DORIS definition of remission in SLE: final recommendations from an international task force. Lupus science & medicine. 2021 Nov; 8[1].AcknowledgementsWe acknowledge the unrestricted project grants received from AstraZeneca, BMS, Eli Lilly, GSK, Janssen, Merck Serono, and UCB to support data collection and project management contributing to this work.Disclosure of InterestsRangi Kandane-Rathnayake: None declared, Vera Golder: None declared, Worawit Louthrenoo: None declared, Yi-Hsing Chen: None declared, Jiacai Cho: None declared, Aisha Lateef: None declared, Laniyati Hamijoyo: None declared, Shue Fen Luo: None declared, Yeong-Jian Jan Wu: None declared, Sandra Navarra Consultant of: Biogen, Boehringer Ingelheim, Astra Zeneca, Grant/research support from: Jannsen, Novartis, Pfizer, Glaxo Smith Kline, Pfizer, Leonid Zamora: None declared, Zhanguo Li Consultant of: Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB Pharma, Grant/research support from: Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB Pharma, Sargunan Sockalingam Consultant of: Pfizer, AstraZeneca, ZP Therapeutics, Grant/research support from: Pfizer, AstraZeneca, ZP Therapeutics, Yasuhiro Katsumata Grant/research support from: GlaxoSmithKline K.K. AstraZeneca K.K. Sanofi K.K. Pfizer Japan Inc., Janssen Pharmaceutical K.K., Chugai Pharmaceutical Co., Ltd., Asahi Kasei Pharma, Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, Masayoshi Harigai Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc.,Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd, Consultant of: AbbVie, Boehringer-ingelheim, Bristol Myers Squibb Co., Kissei Pharmaceutical Co.,Ltd. and Teijin Pharma, Grant/research support from: AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc.,Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekiui Medical, Shionogi & Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Yanjie Hao: None declared, Zhuoli Zhang: None declared, BMDB Basnayake: None declared, Madelynn Chan: None declared, Jun Kikuchi: None declared, Tsutomu Takeuchi Consultant of: AbbVie, Chugai, Mitsubishi-Tanabe, Grant/research support from: AbbVie, Mitsubishi-Tanabe, Eli Lilly Japan, Shereen Oon: None declared, Sang-Cheol Bae: None declared, Sean O’Neill: None declared, Fiona Goldblatt: None declared, Kristine Ng Consultant of: AbbVie, Annie Law: None declared, Nicola Tugnet: None declared, Sunil Kumar: None declared, Michael Tee: None declared, Cherica Tee: None declared, Yoshiya Tanaka Speakers bureau: Behringer-Ingelheim, Eli Lilly, Abbvie, Gilead, AstraZeneca, Bristol-Myers, Chugai, Daiichi-Sankyo, Eisai, Pfizer, Mitsubishi-Tanabe, GlaxoSmithKline, Grant/research support from: Asahi-Kasei, Abbvie, Chugai, Eisai, Takeda, Daiichi-Sankyo, Behringer-Ingelheim, C.S. Lau Speakers bureau: AstraZeneca UK Ltd, Consultant of: AstraZeneca Pharmaceuticals LP, Mandana Nikpour Speakers bureau: Actelion, GSK, Janssen, Pfizer, UCB, Paid instructor for: UCB, Consultant of: Boehringer Ingelheim, Certa Therapeutics, Eli Lilly, GSK, Janssen, Pfizer, UCB, Grant/research support from: Actelion, Astra Zeneca, BMS, GSK, Janssen, UCB, Alberta Hoi Speakers bureau: UCB, Janssen, Sandoz, Eli Lilly, Consultant of: Abbvie, GSK, Grant/research support from: AstraZeneca, GSK, BMS, Janssen, and Merck Serono, Eric F. Morand Speakers bureau: AstraZeneca, EMD Serono, Gilead, Consultant of: AstraZeneca, BristolMyersSquibb, Biogen, Eli Lilly, EMD Serono, Novartis, Grant/research support from: AbbVie, Amgen, AstraZeneca, BristolMyersSquibb, Biogen, Eli Lilly, EMD Serono, Genentech, GSK, Janssen, UCB.

BackgroundSome studies demonstrated that withdrawal of low-dose glucocorticoids in clinically quiescent systemic lupus erythematosus (SLE) patients increased the risk of flare [1]. An international survey of 130 clinicians showed that persistent abnormal serology led to a reluctance to reduce or discontinue medications [2].ObjectivesTo assess the risk of flare and damage accrual after tapering glucocorticoids in serologically active clinically quiescent (SACQ) patients with SLE. Association of other medications with flare in SACQ patients was also analyzed.MethodsWe used data from the Asia Pacific Lupus Collaboration cohort, prospectively collected from SLE patients (ACR/SLICC criteria) observed for at least 2 visits between 2013 and 2020. Disease activity and medication details were captured at enrolment and at routine visits. SACQ was defined at any visit as the state with serological activity (increased anti-dsDNA or hypocomplementemia) but without clinical activity as measured by SLEDAI-2K. Patients treated with 0 to 7.5 mg/day of prednisolone at a SACQ visit were analyzed after stratification according to the initial dosages of prednisolone. Cox proportional hazard models were used to assess the time-dependent relationship between decreasing prednisolone in SACQ patients and disease flares captured with the SELENA flare index at each subsequent visit, as well as subsequent damage accrual (≥1-point increase in SLICC/ACR damage index [SDI]). Each patient was observed for up to 2 years or until each outcome event occurred.ResultsFrom a total of 4,106 patients, 1,850 patients with SACQ and 8,905 visits were analyzed: 742, 271, and 180 patients experienced overall flare, severe flare, and increase in SDI, respectively. Tapering prednisolone was not associated with subsequent overall or severe flare: Each unit decrease in prednisolone dosage (1 mg/day) resulted in adjusted HRs 1.02 (95%CI, 0.99–1.05) and 0.98 (95%CI, 0.96–1.00) for overall and severe flare, respectively, in the group with initial prednisolone dosages of 0–7.5 mg/day. However, among SACQ patients, antimalarial use was significantly associated with reduced overall and severe flare in the groups with initial prednisolone of 0–7.5 or 0–5 mg/day. In addition, immunosuppressive use was significantly associated with reduced severe flare but not overall flare in these groups. Decreasing the dosage of prednisolone was significantly negatively associated with damage accrual in the groups with initial prednisolone dosages of 0–7.5 mg/day (adjusted HR [95%CI], 0.97 [0.96–0.99]) and 5–7.5 mg/day (adjusted HR [95%CI], 0.96 [0.94–0.99]) but not 0–5 mg/day (adjusted HR [95%CI], 0.98 [0.95–1.01]).Table 1.Summary results of association between decreasing the prednisolone dosages and disease flares or damage accrual in SLE patients with SACQInitial prednisolone dosage (mg/day)Overall disease flareSevere disease flareIncrease in SDI0 ≤ prednisolone ≤7.51.02 (0.99–1.05),p= 0.270.98 (0.96–1.00),p= 0.110.97 (0.96–0.99),p< 0.010 ≤ prednisolone ≤51.02 (0.98–1.06),p= 0.410.98 (0.96–1.01),p= 0.280.98 (0.95–1.01),p= 0.145 < prednisolone ≤7.51.01 (0.96–1.06),p= 0.840.98 (0.92–1.03),p= 0.410.97 (0.96–0.99),p< 0.01* HRs (95% CIs) per unit decrease in prednisolone dosages (1 mg/day) were calculated using Cox proportional hazard models and adjusted by initial prednisolone dosage, antimalarial, immunosuppressive, disease duration, SLEDAI-2K, age at visit, gender, and ethnicity.ConclusionTapering prednisolone was not significantly associated with subsequent flare in SLE patients who were SACQ. Antimalarial and immunosuppressive use were associated with reduced risk of flares in SACQ patients. Tapering prednisolone was associated with reduced risk of damage accrual in SACQ patients treated with more than 5 mg/day of prednisolone. These findings suggest glucocorticoid tapering is safe and protective in SLE patients in SACQ.References[1]Rheumatology (Oxford). 2021;60:5517[2]Lupus Sci Med. 2017;4:e000173AcknowledgementsWe acknowledge the unrestricted project grants received from AstraZeneca, BMS, Eli Lilly, GSK, Janssen, Merck Serono, and UCB to support data collection and project management contributing to this work.Disclosure of InterestsYasuhiro Katsumata Speakers bureau: GlaxoSmithKline K.K., AstraZeneca K.K., Sanofi K.K., Pfizer Japan Inc., Janssen Pharmaceutical K.K., Chugai Pharmaceutical Co., Ltd.Asahi Kasei Pharma, Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, Eisuke Inoue Speakers bureau: Bristol-Myers Squibb K.K., Eisai Co., Ltd., Consultant of: Nippontect Systems co., Ltd., Masayoshi Harigai Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc.,Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., Consultant of: AbbVie, Boehringer-ingelheim, Bristol Myers Squibb Co., Kissei Pharmaceutical Co.,Ltd. Teijin Pharma, Grant/research support from: AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc.,Eisai Co., Ltd., Kissei.Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekiui Medical, Shionogi & Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin.Pharma Ltd., Rangi Kandane-Rathnayake: None declared, Worawit Louthrenoo: None declared, Alberta Hoi Speakers bureau: UCB, Janssen, Sandoz, Eli Lilly, Consultant of: Abbvie, GSK, Grant/research support from: AstraZeneca, GSK, BMS, Janssen, Merck Serono, Vera Golder: None declared, C.S. Lau Speakers bureau: AstraZeneca UK Ltd., Consultant of: AstraZeneca Pharmaceuticals LP, Jiacai Cho: None declared, Aisha Lateef: None declared, Yi-Hsing Chen: None declared, Shue Fen Luo: None declared, Yeong-Jian Jan Wu: None declared, Laniyati Hamijoyo: None declared, Zhanguo Li Consultant of: Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB Pharma, Grant/research support from: Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB Pharma, Sargunan Sockalingam Consultant of: Pfizer, AstraZeneca, ZP Therapeutics, Grant/research support from: Pfizer, AstraZeneca, ZP Therapeutics, Sandra Navarra Consultant of: Biogen, Boehringer Ingelheim, Astra Zeneca, Grant/research support from: Jannsen, Novartis, Pfizer, Glaxo Smith Kline, Leonid Zamora: None declared, Yanjie Hao: None declared, Zhuoli Zhang: None declared, Madelynn Chan: None declared, Shereen Oon: None declared, Kristine Ng Consultant of: AbbVie, Jun Kikuchi: None declared, Tsutomu Takeuchi Consultant of: AbbVie, Chugai, Mitsubishi-Tanabe, Grant/research support from: AbbVie, Mitsubishi-Tanabe, Eli Lilly Japan, Fiona Goldblatt: None declared, Sean O’Neill: None declared, Nicola Tugnet: None declared, Annie Law: None declared, Sang-Cheol Bae: None declared, Yoshiya Tanaka Speakers bureau: Behringer-Ingelheim, Eli Lilly, Abbvie, Gilead, AstraZeneca, Bristol-Myers, Chugai, Daiichi-Sankyo, Eisai, Pfizer, Mitsubishi-Tanabe, GlaxoSmithKline, Grant/research support from: Asahi-Kasei, Abbvie, Chugai, Eisai, Takeda, Daiichi-Sankyo, Behringer-Ingelheim, Naoaki Ohkubo: None declared, Sunil Kumar: None declared, Mandana Nikpour Speakers bureau: Actelion, GSK, Janssen, Pfizer, UCB, Paid instructor for: UCB, Consultant of: Boehringer Ingelheim, Certa Therapeutics, Eli.Lilly, GSK, Janssen, Pfizer, UCB, Grant/research support from: Actelion, Astra Zeneca, BMS, GSK, Janssen, UCB, Eric F. Morand Speakers bureau: AstraZeneca, EMD Serono, Gilead, Consultant of: AstraZeneca, BristolMyersSquibb, Biogen, Eli Lilly, EMD Serono, Novartis, Grant/research support from: AbbVie, Amgen, AstraZeneca, BristolMyersSquibb, Biogen, Eli Lilly, EMD Serono, Genentech, GSK, Janssen, UCB.

BackgroundSystemic lupus erythematosus (SLE) has heterogeneous organ manifestations that occur in different combinations at an individual patient level. Current SLE clinical trial eligibility criteria and efficacy endpoints, based on legacy disease activity measures, have multiple weaknesses. Understanding the frequency with which different organ manifestations are represented in contemporary SLE cohorts is required, to allow focus on the most frequent and impactful manifestations of disease in both eligibility criteria and endpoints.ObjectivesTo report the prevalence of disease activity in individual organ domains in SLE patients, both overall and in patients meeting the most common disease activity cut-off for clinical trial eligibility (SLEDAI2K ≥6).MethodsWe used data from a multinational SLE cohort, prospectively collected between 2013 and 2020. We analysed data from 4,102 patients with criteria-defined SLE, who contributed 42,345 visits with complete SLEDAI-2K assessments. Disease activity assessed using SLEDAI-2K was categorised according to activity in 9 organ systems: central nervous system (CNS), vasculitis, musculoskeletal, renal, cutaneous, serositis, serological, haematological, and fever. Proportions of organ-specific disease activity in the overall cohort, and stratified by total SLEDAI-2K ≥6 or <6, were calculated.ResultsIn the overall cohort, 3,659 patients (89.2%) had SLEDAI-2K >0 on at least one visit (31,290 visits, 73.9%). Serological disease activity was the most prevalent in the cohort overall, affecting 75.5% of patients at least once, followed by renal (41.6%), cutaneous (36.5%), musculoskeletal (20%) and haematological (19%) activity. Infrequent active manifestations affecting <5% of patients were serositis (3.4%), vasculitis (3.4%), CNS (3.0%) and fever (3%).We further examined the prevalence of domain-specific disease activity in patient visits stratified by a SLEDAI-2K cut-off of 6 (Table 1). In patient visits with a SLEDAI-2K>6 (n = 10,031 visits, 24% of total) the most common manifestations were serological (90%) and renal (73%), followed by cutaneous (26%) and musculoskeletal (14%). Conversely, 7.3% of visits with renal, 6.7% with cutaneous, 5.8% with haematological and 1.3% with musculoskeletal activity did not have a SLEDAI-2K ≥6 (Table 1).Table 1.Frequencies and percentages of patient visits with specific organ system disease activity, stratified by total SLEDAI score cut-off of ≥6 vs <6.All visitsSLEDAI<6SLEDAI≥6n = 42,345n = 32,314n =10,031p-value*Serological25,745 (60.8%)16,740 (51.8%)9,005 (89.8%)<0.001Renal9,684 (22.9%)2,367 (7.3%)7,317 (72.9%)<0.001Cutaneous4,806 (11.3%)2,158 (6.7%)2,648 (26.4%)<0.001Haematological2,615 (6.2%)1,862 (5.8%)753 (7.5%)<0.001Musculoskeletal1,856 (4.4%)422 (1.3%)1,434 (14.3%)<0.001Serositis255 (0.6%)81 (0.3%)174 (1.7%)<0.001Vasculitis250 (0.6%)0250 (2.5%)<0.001CNS200 (0.5%)0200 (2.0%)<0.001Fever149 (0.4%)59 (0.2%)90 (0.9%)<0.001*P-values derived from Pearson’s Chi-Squared tests.ConclusionSerological, renal, cutaneous, musculoskeletal and haematological manifestations predominate in patients with active SLE in our cohort, with other organs only rarely affected. Measures of improvement in SLE trial endpoints could focus on measuring change in these systems, and omit detailed analysis of rare events. Conversely, a notable proportion of patients with active disease in commonly affected organ domains had SLEDAI-2K <6, meaning they would be excluded from clinical trials. Incorporation of organ-specific activity measures and inclusion criteria for SLE clinical trials may overcome this limitation and improve recruitment to and results of trials.AcknowledgementsWe acknowledge the unrestricted project grants received from AstraZeneca, BMS, Eli Lilly, GSK, Janssen, Merck Serono, and UCB to support data collection and project management contributing to this work.Disclosure of InterestsKathryn Connelly: None declared, Rangi Kandane-Rathnayake: None declared, Vera Golder: None declared, Worawit Louthrenoo: None declared, Yi-Hsing Chen: None declared, Jiacai Cho: None declared, Aisha Lateef: None declared, Laniyati Hamijoyo: None declared, Shue Fen Luo: None declared, Yeong-Jian Jan Wu: None declared, Sandra Navarra Consultant of: Biogen, Boehringer Ingelheim, Astra Zeneca, Grant/research support from: Janssen, Novartis, Pfizer, Glaxo Smith Kline, Pfizer, Leonid Zamora: None declared, Zhanguo Li Consultant of: Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB Pharma, Grant/research support from: Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB Pharma, Sargunan Sockalingam Consultant of: Pfizer, AstraZeneca, ZP Therapeutics, Grant/research support from: Pfizer, AstraZeneca, ZP Therapeutics, Yasuhiro Katsumata Grant/research support from: GlaxoSmithKline K.K. AstraZeneca K.K. Sanofi K.K. Pfizer Japan Inc., Janssen Pharmaceutical K.K., Chugai Pharmaceutical Co., Ltd., Asahi Kasei Pharma, Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, Masayoshi Harigai Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc.,Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd, Consultant of: AbbVie, Boehringer-ingelheim, Bristol Myers Squibb Co., Kissei Pharmaceutical Co.,Ltd. and Teijin Pharma, Grant/research support from: AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc.,Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekiui Medical, Shionogi & Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Yanjie Hao: None declared, Zhuoli Zhang: None declared, Madelynn Chan: None declared, Jun Kikuchi: None declared, Tsutomu Takeuchi Consultant of: AbbVie, Chugai, Mitsubishi-Tanabe, Grant/research support from: AbbVie, Mitsubishi-Tanabe, Eli Lilly Japan, Shereen Oon: None declared, Sang-Cheol Bae: None declared, Fiona Goldblatt: None declared, Sean O’Neill: None declared, Kristine Ng Consultant of: AbbVie, Annie Law: None declared, BMDB Basnayake: None declared, Nicola Tugnet: None declared, Sunil Kumar: None declared, Cherica Tee: None declared, Michael Tee: None declared, Yoshiya Tanaka Speakers bureau: Behringer-Ingelheim, Eli Lilly, Abbvie, Gilead, AstraZeneca, Bristol-Myers, Chugai, Daiichi-Sankyo, Eisai, Pfizer, Mitsubishi-Tanabe, GlaxoSmithKline, Grant/research support from: Asahi-Kasei, Abbvie, Chugai, Eisai, Takeda, Daiichi-Sankyo, Behringer-Ingelheim, C.S. Lau Speakers bureau: AstraZeneca UK Ltd, Consultant of: AstraZeneca Pharmaceuticals LP, Mandana Nikpour Speakers bureau: Actelion, GSK, Janssen, Pfizer, UCB, Paid instructor for: UCB, Consultant of: Actelion, Boehringer Ingelheim, Certa Therapeutics, Eli Lilly, GSK, Janssen, Pfizer, UCB, Grant/research support from: Actelion, Astra Zeneca, BMS, GSK, Janssen, UCB, Alberta Hoi Speakers bureau: UCB, Janssen, Sandoz, Eli Lilly, Consultant of: AbbVie, GSK, Grant/research support from: AstraZeneca, GSK, BMS, Janssen, and Merck Serono, Eric F. Morand Speakers bureau: AstraZeneca, EMD Serono, Gilead, Consultant of: AstraZeneca, BristolMyersSquibb, Biogen, Eli Lilly, EMD Serono, Novartis, Grant/research support from: AbbVie, Amgen, AstraZeneca, BristolMyersSquibb, Biogen, Eli Lilly, EMD Serono, Genentech, GSK, Janssen, UCB.

This work primarily examines the management of wet-preserved archaeological sites in England, through an exploration of value and analysis of current management approaches. The aim is to explore whether the current policy frameworks, in particular the role of preservation in situ, can provide a sustainable future for wet-preserved archaeological sites. This work further seeks to conceptualise the modelling of sustainability, preservation and management decision making in wetland archaeological sites. Looking at the last 40 year of wetland research through the work of the large-scale wetland survey projects, this work initially considers the current understanding of wet archaeological sites in England. It also examines aspects of heritage management through the legislative and policy frameworks and their legacy. This work considers the implications that legislative and policy positions have for the management of wetland archaeological sites and examines the theoretical concepts that underpin them. This includes exploring reflective management, the development of research frameworks, and scoring mechanisms for the designation of sites. It also looks at broader constructs of value through the concepts of cultural and economic values. Three existing archaeological sites, a ringwork at Borough Fen near Peterborough, a marsh fort at Sutton Common near Doncaster and a triple post-alignment near Beccles, will be presented as case studies. These sites serve as examples of how the management of sites has been approached. The results of the case study analysis are used to develop a series of conceptual models looking firstly at sustainability and preservation in situ, and, secondly at preservation, value and decision making. The study concludes that the presumption in favour of preservation in situ can be challenging for wet preserved archaeological sites. Deterioration of the preservation environment can in some cases produce a similar decline in significance. Preservation in situ may therefore not be the most appropriate option for archaeological sites in wetlands.

Many examinations concerning the fatigue life reduction for structural materials of nuclear power plants in water simulated LWR coolants had been carried out after the first paper had been recognized in Japan [1, 2]. Based on these results, the method to evaluate the fatigue damage for the materials exposed to the LWR coolant had been developed. After 1990s in Japan, the Environmental Fatigue Data Committee (EFD) of the Thermal and Nuclear Power Engineering Society (TENPES), the Project on Environmental Fatigue Testing (EFT) supported by the Japan Power Engineering and Inspection Corporation (JAPEIC) and the Japan Nuclear Energy Safety Organization (JNES) and some utility joint studies have investigated the environmental fatigue. In September 2000, the Nuclear Power Generation Safety Management Division of the Agency for Natural Resources and Energy, Ministry of International Trade and Industry issued “Guidelines for Evaluating Fatigue Initiation Life Reduction in the LWR Environment” (hereafter, called “the MITI Guidelines”) [3]. These guidelines include an equation to evaluate environmental fatigue and require electric utilities to consider the environmental effects in their Plant Life Management (PLM) activities. However, the MITI Guidelines do not provide specific and practical techniques for evaluating environmental fatigue under actual plant conditions. Accordingly, TENPES took on the task to produce one. In 2002 TENPES issued the “Guidelines on Environmental Fatigue Evaluation for LWR Component” [4, 5] (hereafter, called “the TENPES Guidelines”) based on the techniques developed by the EFD Committee. A set of Rules, called the Environmental Fatigue Evaluation Method (EFEM), was established in the Codes for Nuclear Power Generation Facilities - Environmental Fatigue Evaluation Method for Nuclear Power Plants (JSME S NF1-2006, EFEM-2006)[6], which was issued in March 2006 by reviewing the equations for the environmental fatigue life correction factor, Fen, specified in the MITI Guidelines, and the techniques for evaluating environmental fatigue specified in the TENPES Guidelines, and considering the new environmental fatigue data including JNES-SS report (August 2005) [7]. The EFEM revised version has been drafted by incorporating the updated knowledge described in JNES-SS report (April 2007) [8] and is scheduled to be issued by the end of 2009. This paper introduces the revision in it and their technical basis. Additionally, future issues are addressed to be considered in the improvement of the EFEM.