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Background:\ud The interleukin-23 (IL-23)/T-helper 17 cell pathway is implicated in psoriatic arthritis pathogenesis. Guselkumab, an IL-23 inhibitor that specifically binds the IL-23 p19 subunit, significantly and safely improved psoriatic arthritis in a phase 2 study. DISCOVER-2 was a phase 3 trial to assess guselkumab in biologic-naive patients with psoriatic arthritis.\ud \ud Methods:\ud This phase 3, double-blind, placebo-controlled study was done at 118 sites in 13 countries across Asia, Europe, and North America. We enrolled biologic-naive patients with active psoriatic arthritis (at least five swollen joints, at least five tender joints, and C-reactive protein ≥0·6 mg/dL) despite standard therapies. Patients were randomly assigned (1:1:1, computer-generated permuted blocks; stratified by baseline disease-modifying antirheumatic drug use and C-reactive protein concentration) to subcutaneous injections of guselkumab 100 mg every 4 weeks; guselkumab 100 mg at weeks 0, 4, then every 8 weeks; or placebo. The primary endpoint was American College of Rheumatology 20% improvement (ACR20) response at week 24 in all patients per assigned treatment group. Safety was assessed in all patients per treatment received. This trial is registered at ClinicalTrials.gov, NCT03158285 (active, not recruiting).\ud \ud Findings:\ud From July 13, 2017, to Aug 3, 2018, 1153 patients were screened, of whom 741 were randomly assigned to receive guselkumab every 4 weeks (n=246), every 8 weeks (n=248), or placebo (n=247). One patient in the every 4 weeks group and one in the placebo group did not start treatment, and the remaining 739 patients started treatment; 716 patients continued treatment up to week 24. Significantly greater proportions of patients in the guselkumab every 4 weeks group (156 [64%] of 245 [95% CI 57–70]) and every 8 weeks group (159 [64%] of 248 [58–70]) than in the placebo group (81 [33%] of 246 [27–39]) achieved an ACR20 response at week 24 (percentage differences vs placebo 31% [95% CI 22–39] for the every 4 weeks group and 31% [23–40] for the every 8 weeks group; both p

Background and objective: To present a structured approach for assessing stakeholder perceptions and implementing the approach in guideline development. Methods: This work was carried out by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Equity and Stakeholder Engagement Project Groups through brainstorming and iterative frameworks, stakeholder engagement, pilot testing, refinement of ideas, using input from workshops, and discussions at GRADE Working Group meetings to produce this document, which constitutes a GRADE conceptual article on implementation. Results: We introduce the FACE implementation criteria, feasibility, acceptability, cost, and equity; priority; and "intent to implement" criterion. We outline the implementation importance of networks and approaches to patient and other stakeholder engagement. Implementation is often highly contextual and can benefit from stakeholder engagement and other assessments. Our FACE approach provides stakeholder questions and language to inform guideline implementation and tools. Conclusion: The FACE criteria propose a series of knowledge translation questions to guide the assessment of implementation for evidence-based guidelines. It is desirable for guideline developers to use a conceptual approach, such as FACE, to tailor implementation and inform end of guideline dissemination and knowledge translation activities. (C) 2020 Published by Elsevier Inc.

Earthworms are an important soil taxon as ecosystem engineers, providing a variety of crucial ecosystem functions and services. Little is known about their diversity and distribution at large spatial scales, despite the availability of considerable amounts of local-scale data. Earthworm diversity data, obtained from the primary literature or provided directly by authors, were collated with information on site locations, including coordinates, habitat cover, and soil properties. Datasets were required, at a minimum, to include abundance or biomass of earthworms at a site. Where possible, site-level species lists were included, as well as the abundance and biomass of individual species and ecological groups. This global dataset contains 10,840 sites, with 184 species, from 60 countries and all continents except Antarctica. The data were obtained from 182 published articles, published between 1973 and 2017, and 17 unpublished datasets. Amalgamating data into a single global database will assist researchers in investigating and answering a wide variety of pressing questions, for example, jointly assessing aboveground and belowground biodiversity distributions and drivers of biodiversity change., H.R.P.P., B.K-R., and the sWorm workshops were supported by the sDiv [Synthesis Centre of the German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig (DFG FZT 118)]. H.R.P.P., O.F. and N.E. acknowledge funding by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 677232 to NE). K.S.R. and W.H.v.d.P. were supported by ERC-ADV grant 323020 to W.H.v.d.P. Also supported by iDiv (DFG FZT118) Flexpool proposal 34600850 (C.A.G. and N.E.); the Academy of Finland (285882) and the Natural Sciences and Engineering Research Council of Canada (postdoctoral fellowship and RGPIN-2019-05758) (E.K.C.); German Federal Ministry of Education and Research (01LO0901A) (D.J.R.); ERC-AdG 694368 (M.R.); the TULIP Laboratory of Excellence (ANR-10-LABX-41) (M.L); and the BBSRC David Phillips Fellowship to F.T.d.V. (BB/L02456X/1). In addition, data collection was funded by the Russian Foundation for Basic Research (12-04-01538-а, 12-04-01734-a, 14-44-03666-r_center_a, 15-29-02724-ofi_m, 16-04-01878-a 19-05-00245, 19-04-00-609-a); Tarbiat Modares University; Aurora Organic Dairy; UGC(NERO) (F. 1-6/Acctt./NERO/2007-08/1485); Natural Sciences and Engineering Research Council (RGPIN-2017-05391); Slovak Research and Development Agency (APVV-0098-12); Science for Global Development through Wageningen University; Norman Borlaug LEAP Programme and International Atomic Energy Agency (IAEA); São Paulo Research Foundation - FAPESP (12/22510-8); Oklahoma Agricultural Experiment Station; INIA - Spanish Agency (SUM 2006-00012-00-0); Royal Canadian Geographical Society; Environmental Protection Agency (Ireland) (2005-S-LS-8); University of Hawai’i at Mānoa (HAW01127H; HAW01123M); European Union FP7 (FunDivEurope, 265171; ROUTES 265156); U.S. Department of the Navy, Commander Pacific Fleet (W9126G-13-2-0047); Science and Engineering Research Board (SB/SO/AS-030/2013) Department of Science and Technology, New Delhi, India; Strategic Environmental Research and Development Program (SERDP) of the U.S. Department of Defense (RC-1542); Maranhão State Research Foundation (FAPEMA 03135/13, 02471/17); Coordination for the Improvement of Higher Education Personnel (CAPES 3281/2013); Ministry of Education, Youth and Sports of the Czech Republic (LTT17033); Colorado Wheat Research Foundation; Zone Atelier Alpes, French National Research Agency (ANR-11-BSV7-020-01, ANR-09-STRA-02-01, ANR 06 BIODIV 009-01); Austrian Science Fund (P16027, T441); Landwirtschaftliche Rentenbank Frankfurt am Main; Welsh Government and the European Agricultural Fund for Rural Development (Project Ref. A AAB 62 03 qA731606); SÉPAQ, Ministry of Agriculture and Forestry of Finland; Science Foundation Ireland (EEB0061); University of Toronto (Faculty of Forestry); National Science and Engineering Research Council of Canada; Haliburton Forest & Wildlife Reserve; NKU College of Arts & Sciences Grant; Österreichische Forschungsförderungsgesellschaft (837393 and 837426); Mountain Agriculture Research Unit of the University of Innsbruck; Higher Education Commission of Pakistan; Kerala Forest Research Institute, Peechi, Kerala; UNEP/GEF/TSBF-CIAT Project on Conservation and Sustainable Management of Belowground Biodiversity; Ministry of Agriculture and Forestry of Finland; Complutense University of Madrid/European Union FP7 project BioBio (FPU UCM 613520); GRDC; AWI; LWRRDC; DRDC; CONICET (National Scientific and Technical Research Council) and FONCyT (National Agency of Scientific and Technological Promotion) (PICT, PAE, PIP), Universidad Nacional de Luján y FONCyT (PICT 2293 (2006)); Fonds de recherche sur la nature et les technologies du Québec (131894); Deutsche Forschungsgemeinschaft (SCHR1000/3-1, SCHR1000/6-1, 6-2 (FOR 1598), WO 670/7-1, WO 670/7-2, & SCHA 1719/1-2), CONACYT (FONDOS MIXTOS TABASCO/PROYECTO11316); NSF (DGE-0549245, DGE-0549245, DEB-BE-0909452, NSF1241932, LTER Program DEB-97–14835); Institute for Environmental Science and Policy at the University of Illinois at Chicago; Dean’s Scholar Program at UIC; Garden Club of America Zone VI Fellowship in Urban Forestry from the Casey Tree Endowment Fund; J.E. Weaver Competitive Grant from the Nebraska Chapter of The Nature Conservancy; The College of Liberal Arts and Sciences at Depaul University; Elmore Hadley Award for Research in Ecology and Evolution from the UIC Dept. of Biological Sciences, Spanish CICYT (AMB96-1161; REN2000-0783/GLO; REN2003-05553/GLO; REN2003-03989/GLO; CGL2007-60661/BOS); Yokohama National University; MEXT KAKENHI (25220104); Japan Society for the Promotion of Science KAKENHI (25281053, 17KT0074, 25252026); ADEME (0775C0035); Ministry of Science, Innovation and Universities of Spain (CGL2017-86926-P); Syngenta Philippines; UPSTREAM; LTSER (Val Mazia/Matschertal); Marie Sklodowska Curie Postdoctoral Fellowship (747607); National Science & Technology Base Resource Survey Project of China (2018FY100306); McKnight Foundation (14–168); Program of Fundamental Researches of Presidium of Russian Academy of Sciences (AААА-A18–118021490070–5); Brazilian National Council for Scientific and Technological Development (CNPq 310690/2017–0, 404191/2019–3, 307486/2013–3); French Ministry of Foreign and European Affairs; Bavarian Ministry for Food, Agriculture and Forestry (Project No B62); INRA AIDY project; MIUR PRIN 2008; Idaho Agricultural Experiment Station; Estonian Science Foundation; Ontario Ministry of the Environment, Canada; Russian Science Foundation (16-17-10284); National Natural Science Foundation of China (41371270); Australian Research Council (FT120100463); USDA Forest Service-IITF.

Objective. Evaluate enthesitis, physical function, and health-related quality of life (HRQOL) among patients with psoriatic arthritis (PsA) who are naive to anti-tumor necrosis factor agents. Methods. In PSUMMIT 1 and 2, patients with PsA were randomized to placebo or ustekinumab 45 mg or 90 mg. Enthesitis was assessed at weeks 0 and 24 (Maastricht Ankylosing Spondylitis Enthesitis Score). Assessments included Health Assessment Questionnaire-Disability Index (HAQ-DI), Medical Outcomes Study Short Form-36 (SF-36) physical component summary/mental component summary (PCS/MCS), and American College of Rheumatology 20 (ACR20). Results. At Week 24, 21 had worsened enthesitis, 158 had improved enthesitis, and 412 had unchanged enthesitis. Improved enthesitis was associated with improvements in HAQ-DI and SF-36 MCS. Results were similar for ACR20 responders and nonresponders. Conclusion. Improvement in enthesitis at Week 24 was associated with improvements in physical function/HRQOL regardless of ACR20 response.

ZnO nanoparticles are immobilized on the chitosan matrix by an in situ sol–gel conversion of precursor molecules in a single step. Three different composites are prepared by varying the concentration of sodium hydroxide with same quantity of chitosan and zinc acetate dihydrate. The composites were characterized by FTIR, UV–visible spectra, and XRD. The observed decrease in the band width corresponding to OH and NH 2 group in the composites is ascribed to the reduction of hydrogen bond due to the presence of ZnO nanoparticles. The direct evidence of the immobilization of nano ZnO particles in the matrix was identified by SEM. The average particle size values obtained for the nanoparticles, using Debye–Scherrer equation from XRD, is in the range 10–18 nm. Optical studies proved that all the three composites studied have the same band gap energy (3.28 eV) in agreement with the reported values. We observed that the composites possess excellent antimicrobial activity against Gram negative bacteria Escherichia coli ( E. coli ) and Gram positive bacteria Staphylococcus aureus ( S. aureus ) than chitosan. Based on the above studies, the biocompatible, eco-friendly and low-cost composite powder could be applied in various fields as an antimicrobial agent.

Introduction The European Centre for Disease Prevention and Control is developing evidence-based guidance for voluntary screening, treatment and vaccine prevention of infectious diseases for newly arriving migrants to the European Union/European Economic Area. The objective of this systematic review protocol is to guide the identification, appraisal and synthesis of the best available evidence on prevention and assessment of the following priority infectious diseases: tuberculosis, HIV, hepatitis B, hepatitis C, measles, mumps, rubella, diphtheria, tetanus, pertussis, poliomyelitis (polio), Haemophilus influenza disease, strongyloidiasis and schistosomiasis. Methods and analysis The search strategy will identify evidence from existing systematic reviews and then update the effectiveness and cost-effectiveness evidence using prospective trials, economic evaluations and/or recently published systematic reviews. Interdisciplinary teams have designed logic models to help define study inclusion and exclusion criteria, guiding the search strategy and identifying relevant outcomes. We will assess the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Ethics and dissemination There are no ethical or safety issues. We anticipate disseminating the findings through open-access publications, conference abstracts and presentations. We plan to publish technical syntheses as GRADEpro evidence summaries and the systematic reviews as part of a special edition open-access publication on refugee health. We are following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols reporting guideline. This protocol is registered in PROSPERO: CRD42016045798.

ObjectiveTo identify genetic associations with severity of radiographic damage in ankylosing spondylitis (AS).MethodWe studied 1537 AS cases of European descent; all fulfilled the modified New York Criteria. Radiographic severity was assessed from digitised lateral radiographs of the cervical and lumbar spine using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). A two-phase genotyping design was used. In phase 1, 498 single nucleotide polymorphisms (SNPs) were genotyped in 688 cases; these were selected to capture >90% of the common haplotypic variation in the exons, exon-intron boundaries, and 5 kb flanking DNA in the 5' and 3' UTR of 74 genes involved in anabolic or catabolic bone pathways. In phase 2, 15 SNPs exhibiting p

OBJECTIVE: To use high-density genotyping to investigate the genetic associations of acute anterior uveitis (AAU) in patients with and those without ankylosing spondylitis (AS). METHODS: We genotyped samples from 1,711 patients with AAU (either primary or combined with AS), 2,339 AS patients without AAU, and 10,000 control subjects on an Illumina Immunochip Infinium microarray. We also used data for AS patients from previous genome-wide association studies to investigate the AS risk locus ANTXR2 for its putative effect in AAU. ANTXR2 expression in mouse eyes was investigated by real-time quantitative reverse transcription-polymerase chain reaction. RESULTS: A comparison between all patients with AAU and healthy control subjects showed strong association over HLA-B, corresponding to the HLA-B27 tag single-nucleotide polymorphism rs116488202. The association of 3 non-major histocompatibility complex loci, IL23R, the intergenic region 2p15, and ERAP1, reached genome-wide significance (P < 5 × 10(-8) ). Five loci harboring the immune-related genes IL10-IL19, IL18R1-IL1R1, IL6R, the chromosome 1q32 locus harboring KIF21B, as well as the eye-related gene EYS, were also associated, reaching a suggestive level of significance (P < 5 × 10(-6) ). Several previously confirmed AS associations demonstrated significant differences in effect size between AS patients with AAU and AS patients without AAU. ANTXR2 expression varied across eye compartments. CONCLUSION: These findings of both novel AAU-specific associations and associations shared with AS demonstrate overlapping but also distinct genetic susceptibility loci for AAU and AS. The associations in IL10 and IL18R1 are shared with inflammatory bowel disease, suggesting common etiologic pathways.

UNSW Water Research Laboratory Research Report No. 255

UNSW Water Research Laboratory Technical Report No. 2013/09

Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 × 10(-8) in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 × 10(-6) overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides.

© Australasian Coasts and Ports 2019 Conference. All rights reserved. This paper presents a detailed hydrodynamic and water quality model to simulate ecological processes in the Hunter River estuary. Following an extensive 3-year multi-disciplinary field campaign, the model was developed to assess total catchment management options. The model outcomes are linked to existing water sharing plans, pollution reduction plans and coastal reforms underway in NSW. Initially a detailed scoping study was undertaken to determine the values and requirements of the key stakeholders across the catchment. Data gaps were subsequently prioritised, and an inter-agency modelling oversight committee was formed to ensure that the modelling tools would be accepted across the region. Following these developmental stages, a field program was initiated which included: estuary wide flow gauging and water quality assessments, microbial linkages, ecotoxicological assessments, sedimentation dynamics, DNA sequencing, qPCR analyses, catchment hydrological flux measurements, nutrient mesocosm experiments, bathymetry surveys and the development of crop irrigation modules. The field data analyses resulted in a conceptual model of the eco-hydraulics of the estuary. A robust numerical model was formulated through an extensive process of external peer review. A source model was selected that ensured the broadest flexibility and ongoing usage rates. A multi-disciplinary approach was undertaken to ensure the model represents a wide range of estuarine processes. The final model is currently undergoing additional peer review, calibration/validation and simulation testing.

Systemic lupus erythematosus (SLE) is a highly prevalent autoimmune disease and coronary artery disease (CAD) is a complication of SLE which is often crucial for the patient's prognosis. It is hypothesized that apolipoprotein E (Apo E), which is involved in cholesterol metabolism, might play a role in this process.Patients with SLE registered at the University of Toronto Lupus Clinic who had DNA available for study had their Apo E genotype determined. Each case was assessed for the presence of CAD, and Apo E allele frequencies in patients with SLE were compared with data from the general population. Age at onset and disease duration of CAD were also recorded and compared between groups.DNA was stored from 152 patients, of whom 38 (25%) had CAD. There was no difference in the frequencies of the Apo E isoforms between SLE patients and the general population. Patients with the E2 allele developed CAD after a mean +/-SD of 6.0+/-1.9 yrs compared with 14.5+/-5.4 yrs in those with E3/3 (p0.01).The distribution of Apo E genotypes in SLE is not significantly different from that of the North American population. In SLE, Apo E2 was associated with a more rapid development of CAD. Therefore, Apo E2 might interact with other disease-related factors to accelerate the onset of CAD in some patients with SLE and as such might be an additional marker of risk in this population.