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To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files, OBJECTIVE: To determine the level of agreement of disease flare severity (distinguishing severe, moderate, and mild flare and persistent disease activity) in a large paper-patient exercise involving 988 individual cases of systemic lupus erythematosus. METHODS: A total of 988 individual lupus case histories were assessed by 3 individual physicians. Complete agreement about the degree of flare (or persistent disease activity) was obtained in 451 cases (46%), and these provided the reference standard for the second part of the study. This component used 3 flare activity instruments (the British Isles Lupus Assessment Group [BILAG] 2004, Safety of Estrogens in Lupus Erythematosus National Assessment [SELENA] flare index [SFI] and the revised SELENA flare index [rSFI]). The 451 patient case histories were distributed to 18 pairs of physicians, carefully randomized in a manner designed to ensure a fair case mix and equal distribution of flare according to severity. RESULTS: The 3-physician assessment of flare matched the level of flare using the 3 indices, with 67% for BILAG 2004, 72% for SFI, and 70% for rSFI. The corresponding weighted kappa coefficients for each instrument were 0.82, 0.59, and 0.74, respectively. We undertook a detailed analysis of the discrepant cases and several factors emerged, including a tendency to score moderate flares as severe and persistent activity as flare, especially when the SFI and rSFI instruments were used. Overscoring was also driven by scoring treatment change as flare, even if there were no new or worsening clinical features. CONCLUSION: Given the complexity of assessing lupus flare, we were encouraged by the overall results reported. However, the problem of capturing lupus flare accurately is not completely solved.

Made available in DSpace on 2022-04-28T17:22:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-10-01 Janssen Research & Development, LLC Objectives. To assess efficacy, pharmacokinetics (PK) and safety of intravenous (i.v.) golimumab in patients with polyarticular-course JIA (pc-JIA). Methods. Children aged 2 to = 2months received 80 mg/m(2) golimumab at weeks 0, 4, then every 8 weeks through week 52 plus MTX weekly through week 28. The primary and major secondary endpoints were PK exposure and model-predicted steady-state area under the curve (AUC(ss)) over an 8-week dosing interval at weeks 28 and 52, respectively. JIA ACR response and safety were also assessed. Results. In total, 127 children were treated with i.v. golimumab. JIA ACR 30, 50, 70, and 90 response rates were 84%, 80%, 70% and 47%, respectively, at week 28 and were maintained through week 52. Golimumab serum concentrations and AUC(ss) were 0.40 mu g/ml and 399 mu g. day/ml at week 28. PK exposure was maintained at week 52. Steady-state trough golimumab concentrations and AUC(ss) were consistent across age categories and comparable to i.v. golimumab dosed 2mg/kg in adults with rheumatoid arthritis. Golimumab antibodies and neutralizing antibodies were detected via a highly sensitive drug-tolerant assay in 31% (39/125) and 19% (24/125) of patients, respectively. Median trough golimumab concentration was lower in antibody-positive vs antibody-negative patients. Serious infections were reported in 6% of patients, including one death due to septic shock. Conclusion. Body surface area-based dosing of i.v. golimumab was well tolerated and provided adequate PK exposure for clinical efficacy in paediatric patients with active pc-JIA. IRCCS Ist Giannina Gaslini Clin Pediat & Reumatol, PRINTO, Genoa, Italy Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH USA Univ Autonoma Chihuahua, Fac Med, Circuito Univ Campus 2, Chihuahua, Mexico Panorama Med Ctr, Cape Town, South Africa Hosp Mexico Americano, Ctr Reumatol & Autoinmunidad CREA, Guadalajara, Jalisco, Mexico Ctr Med Privado Reumatol, Rheumatol Sect, San Miguel De Tucuman, Tucuman, Argentina Randall Childrens Hosp Legacy Emanuel, Portland, OR USA Univ Calgary, Alberta Childrens Hosp, Cumming Sch Med, Dept Pediat, Calgary, AB, Canada Pontificia Univ Catolica Chile, Sch Med, Dept Pediat Infect Dis & Immunol, Santiago, Chile Hosp Pedro de Elizalde, Rheumatol Sect, Buenos Aires, DF, Argentina Univ Utah, Pediat Rheumatol, Salt Lake City, UT USA Bashkir State Med Univ Minist Healthcare Russian, Fed State Budget Educ Inst Higher Educ, Ufa, Russia Univ Cape Town, Red Cross War Mem Childrens Hosp, Cape Town, South Africa Univ Cape Town, Groote Schuur Hosp, Paediat Rheumatol, Cape Town, South Africa Clin Hosp 5, Pediat Dept, Tolyatti, Russia Univ Fed Sao Paulo, Escola Paulista Med, Pediat, Sao Paulo, Brazil Inst CAICI, Rheumatol, Rosario, Argentina Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil UNESP, Hosp Clin Botucatu Med Univ, Paediat Dept, Botucatu, SP, Brazil Hosp Infantil Mexico Dr Federico Gomez, Med Interna & Reumatol, Mexico City, DF, Mexico Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA Janssen Res & Dev LLC, Spring House, PA USA Janssen Res & Dev LLC, Raritan, NJ USA Univ Genoa, Dipartimento Neurosci Riabilitaz Oftalmol Genet &, Genoa, Italy UNESP, Hosp Clin Botucatu Med Univ, Paediat Dept, Botucatu, SP, Brazil

Made available in DSpace on 2021-06-25T11:50:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-03-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The concept of Developmental Origins of Health and Disease (DOHaD) states that exposure to malnutrition early in life increase the incidence of non-communicable chronic diseases throughout the lifespan. In this study, a reduction in serum testosterone and an increase in estrogen levels were shown in older rats born to protein malnourished dams (6% protein in the diet) during gestation and lactation. Intraprostatic levels of reduced glutathione were decreased, while tissue expression of glutathione S-transferase pi and sulfiredoxin-1 were increased in these animals. Strong immunostaining for alfametilacil CoA racemase (AMACR), vascular endothelial growth factor-A (VEGF-A), and aquaporin-1 (AQP1) was also observed. In silica analysis confirmed commonly deregulated proteins in the ventral prostate of old rats and patients with prostate cancer. In conclusion, the increase in oxidative stress associated with an imbalance of sex hormones may contribute to prostate carcinogenesis in offspring, highlighting early-life malnutrition as a key risk factor for this malignance. Sao Paulo State Univ, Inst Biosci, Dept Struct & Funct Biol, Botucatu, SP, Brazil Univ Calgary, Cumming Sch Med, Snyder Inst Chron Dis, Calgary, AB, Canada Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Biol Reprod, Mexico City, DF, Mexico Sao Paulo State Univ, Inst Biosci, Dept Struct & Funct Biol, Botucatu, SP, Brazil FAPESP: 2017/01063-7 FAPESP: 2016/08789-0 CNPq: 310663/2018-0

Made available in DSpace on 2021-06-25T12:37:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-03-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Eyes High Doctoral Recruitment Scholarship Exercise intensity variations throughout a cycling time trial (TT) might be influenced by subject's functional state. Purpose The current study characterized the performance fatigability etiology, immediately after exercise cessation, and its relation to the dynamic changes in muscle O-2 saturation (SmO2) at different TT phases. Methods Twelve males performed three separated TT of different distances, in a crossover counterbalanced design, until the end of the fast-start (FS, 827 +/- 135 m), even-pace (EP, 3590 +/- 66 m), or end-spurt (ES, 4000 m) TT phases. Performance fatigability was characterized by using isometric maximal voluntary contractions (IMVC), whereas the maximal voluntary activation (VA) and contractile function of knee extensors (e.g., peak torque of potentiated twitches [TwPt]) were evaluated using electrically evoked contractions performed before and immediately after each exercise bouts. SmO2, power output (PO), and EMG were also recorded. Results Immediately after the FS phase, there were lower values for IMVC (-23%), VA (-8%), and TwPt (-43%) (all P < 0.001), but no further changes were measured after EP (IMVC, -28%; VA, -8%; TwPt, -38%). After the ES phase, IMVC (-34%) and TwPt (-59%) further decreased compared with the previous phases (P < 0.05). There were lower SmO2 and higher EMG/PO values during FS and ES compared with EP phase. Conclusion FS and EP phases had similar performance fatigability etiology, but ES showed further impairments in contractile function. This later finding might be due to the abrupt changes in SmO2 and EMG/PO because of the high exercise intensity during the ES, which elicited maximal decline in contractile function at the finish line. Univ Calgary, Fac Kinesiol, KNB 434,2500 Univ Dr NW, Calgary, AB T2N 1N4, Canada Univ Sao Paulo, Sch Phys Educ & Sport GEDAE USP, Endurance Performance Res Grp GEDAE USP, Sao Paulo, Brazil UNESP Univ Estadual Paulista, Fac Sci, Dept Phys Educ, Bauru, SP, Brazil Univ Lyon, Lab Interuniv Biol Motricite, UJM St Etienne, St Etienne, France Inst Univ France IUF, Paris, France UNESP Univ Estadual Paulista, Fac Sci, Dept Phys Educ, Bauru, SP, Brazil FAPESP: 2017/22053-0 FAPESP: 2016/26281-4 FAPESP: 2016/02683-6

Made available in DSpace on 2018-11-26T15:45:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-11-01 Alberta Livestock and Meat Agency (ALMA), Canada Natural Sciences and Engineering Research Council of Canada (NSERC) University of Calgary, Canada NSERC-CREATE Host Parasite Interactions (HPI) graduate training program Next-generation deep amplicon sequencing, or metabarcoding, has revolutionized the study of microbial communities in humans, animals and the environment. However, such approaches have yet to be applied to parasitic helminth communities. We recently described the first example of such a method - nemabiome sequencing - based on deep-amplicon sequencing of internal transcribed spacer 2 (ITS-2) rDNA, and validated its ability to quantitatively assess the species composition of cattle gastro-intestinal nematode (GIN) communities. Here, we present the first application of this approach to explore GIN species diversity and the impact of anthelmintic drug treatments. First, we investigated GIN species diversity in cow-calf beef cattle herds in several different regions, using coproculture derived L3s. A screen of 50 Canadian beef herds revealed parasite species diversity to be low overall. The majority of parasite communities were comprised of just two species; Ostertagia ostertagi and Cooperia oncophora. Cooperia punctata was present at much lower levels overall, but nevertheless comprised a substantive part of the parasite community of several herds in eastern Canada. In contrast, nemabiome sequencing revealed higher GIN species diversity in beef calves sampled from central/south-eastern USA and Sao Paulo State, Brazil. In these regions C. punctata predominated in most herds with Haemonchus placei predominating in a few cases. Ostertagia ostertagi and C. oncophora were relatively minor species in these regions in contrast to the Canadian herds. We also examined the impact of routine macrocyclic lactone pour-on treatments on GIN communities in the Canadian beef herds. Low treatment effectiveness was observed in many cases, and nemabiome sequencing revealed an overall increase in the proportion of Cooperia spp. relative to O. ostertagi post-treatment. This work demonstrates the power of nemabiome metabarcoding to provide a detailed picture of GIN parasite community structure in large sample sets and illustrates its potential use in research, diagnostics and surveillance. (C) 2017 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology. Univ Calgary, Fac Vet Med, Dept Comparat Biol & Expt Med, Calgary, AB, Canada Merck Anim Hlth, Calgary, AB, Canada Sao Paulo State Univ, Jaboticabal, SP, Brazil Univ Arkansas, Dept Anim Sci, Fayetteville, AR 72701 USA Sao Paulo State Univ, Jaboticabal, SP, Brazil Alberta Livestock and Meat Agency (ALMA), Canada: 2011R024R Alberta Livestock and Meat Agency (ALMA), Canada: 2014R027R Natural Sciences and Engineering Research Council of Canada (NSERC): RGPIN/371529-2209

Made available in DSpace on 2020-12-10T19:51:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-02-01 Natural Sciences and Engineering Research Council (NSERC) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) It is well established that hypothalamic GnRH (gonadotropin-releasing hormone) is one of the key peptides involved in the neuroendocrine control of testicular development and spermatogenesis. However, the role of GnRH as a paracrine regulator of testicular function has not been fully investigated. The present study demonstrates the presence of GnRH and its receptors in the zebrafish (Danio rerio) testis, and provides information on direct action of native GnRH isoforms (GnRH2 and GnRH3) on different stages of spermatogenesis in this model. Both GnRH2 and GnRH3 stimulated basal spermatogenesis by increasing numbers of type A(und) spermatogonia, spermatozoa, and testosterone release, and in this study GnRH2 exerted higher relative activity than GnRH3. Next, we evaluated the effects of GnRH isoforms on human chorionic gonadotropin (hCG)- and follicle-stimulating hormone (Fsh)-induced spermatogenesis. The 2 GnRH isoforms were found to have different effects on Fsh- and hCG-induced response depending on the stage of spermatogenesis and concentration of the peptides. The results provide strong support for the hypothesis that locally produced GnRH2 and GnRH3 are important components of the complex multifactorial system that regulates testicular germinal cell development and function in adult zebrafish. Univ Calgary, Dept Biol Sci, 2500 Univ Dr NW, Calgary, AB T2N 1N4, Canada Sao Paulo State Univ, Dept Morphol, Reprod & Mol Biol Grp, Botucatu, SP, Brazil Sao Paulo State Univ, Dept Morphol, Reprod & Mol Biol Grp, Botucatu, SP, Brazil Natural Sciences and Engineering Research Council (NSERC): 1021837 FAPESP: 17/15793-7 FAPESP: 18/15319-6

Made available in DSpace on 2021-06-25T12:29:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-15 Natural Sciences and Engineering Research Council (NSERC) of Canada Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Gonadotropin-inhibitory hormone (Gnih) is known to play a role in the regulation of reproduction in vertebrates by influencing gonadotmpin release and synthesis. While the endocrine actions of Gnih have been identified in several species, its paracrine/autocrine effects in the control of spermatogenesis are less defined. We have used ex vivo culture of zebrafish testis to investigate the role of gonadal zebrafish Gnih (zGnih) in the regulation of the spermatogenic process. We used FACScan cell cycle analysis, morphometric quantifications, BrdU incorporation and caspase-3 activity assays as well as measuring 11-Ketotestosterone (11-KT) level in the culture media. FACScan analysis and morphometric quantification results demonstrated direct action of zGnih on basal and gonadotropin (Lh and Fsh)-induced spermatogenesis. Treatment with zGnih (10 nM) significantly decreased the number of G0/G1 cells after 7-days of culture while no significant changes were found in the proportion area of spermatogonia cell types. Investigation of DNA synthesis using BrdU (5-Bromo-2'-Deoxyuridine) labeling showed that treatment with zGnih (10 nM) significantly decreased proliferative activity of type A spermatogonia, while increased the mitotic activity of type B spermatogonia. We also showed that treatment with zGnih (100 nM) completely eliminated 11-KT release induced by 100 ng/ml Fsh. Treatment with zGnih (10 and 100 nM) also inhibited both hCG and Fsh-induced spermatogenesis. These results, plus our previous findings, demonstrate that zGnih produced locally in the testis is a component of a complex multifactorial system that regulates testicular function in zebrafish. Univ Calgary, Dept Biol Sci, 2500 Univ Dr NW, Calgary, AB T2N 1N4, Canada Sao Paulo State Univ, Dept Morphol, Reprod & Mol Biol Grp, Botucatu, SP, Brazil Sao Paulo State Univ, Dept Morphol, Reprod & Mol Biol Grp, Botucatu, SP, Brazil Natural Sciences and Engineering Research Council (NSERC) of Canada: 1021837 FAPESP: 17/15793-7 FAPESP: 18/15319-6

WOS: 000468739200001 In this paper, we introduce a method based on recommendation systems to predict the structure of Gene Regulatory Networks (GRNs) making use of data from multiple sources. Our method is based on collaborative filtering approach enhanced with multiple criteria to predict the relationships of genes, i.e., which genes regulate others. We conduct experiments on two data sets to demonstrate the applicability and sustainability of our proposal. The first data set is composed of microarray data and Transcription Factor (TF) binding data, and it is evaluated by precision, recall and the F1-measure. The second data set is the Dream4 In Silico Network Challenge data set, and it is evaluated by the measures that are used during the challenge, namely the Area Under Precision and Recall curve (AUC-PR), the Area Under the Receiver Operating Characteristic curve (AUC-ROC) and their averages. The experimental results show that applying algorithms from the recommendation systems domain on the problem of inference of GRN structures is effective. Also, we observed that combining information from multiple data sets gives better results. TUBITAK-BIDEB 2214/A program This research is supported by TUBITAK-BIDEB 2214/A program.

Cortisol is the major endocrine factor mediating the inhibitory effects of stress on vertebrate reproduction. It is well known that cortisol affects reproduction by interacting with the hypothalamic&ndash, pituitary&ndash, gonads axis, leading to downstream inhibitory and stimulatory effects on gonads. However, the mechanisms are not fully understood. In this study, we provide novel data demonstrating the stimulatory effects of cortisol on spermatogenesis using an ex vivo organ culture system. The results revealed that cortisol treatment did not modulate basal androgen production, but it influenced transcript levels of a selected number of genes involved in the zebrafish testicular function ar (androgen receptor), star (steroidogenic acute regulatory), cyp17a1 (17&alpha, hydroxylase/17,20 lyase/17,20 desmolase), cyp11a2 (cytochrome P450, family 11, subfamily A, polypeptide 2), hsd11b2 (11-beta hydroxysteroid dehydrogenase), cyp2k22 (cytochrome P450, family 2, subfamily K, polypeptide 22), fkbp5 (FKBP prolyl isomerase 5), gr&alpha, (glucocorticoid receptor alpha), and gr&beta, (glucocorticoid receptor beta) in a short-term culture. We also showed that cortisol stimulates spermatogonial proliferation and differentiation in an androgen independent manner as well as promoting meiosis and spermiogenesis by increasing the number of spermatozoa in the testes. Moreover, we demonstrated that concomitant treatment with RU 486, a potent glucocorticoid receptor (Gr) antagonist, did not affect the cortisol effects on spermatogonial differentiation but blocked the induced effects on meiosis and spermiogenesis. Supporting the Gr-mediated effects, RU 486 nullified the cortisol-induced expression of sycp3l (synaptonemal complex protein 3), a marker for the meiotic prophase that encodes a component of the synaptonemal complex. This is consistent with in silico analysis that found 10 putative GREs (glucocorticoid response elements) upstream of the zebrafish sycp3l. Finally, we also showed that gr&alpha, mRNA is expressed in Sertoli and Leydig cells, but also in several types of germ cells, including spermatogonia and spermatocytes. Altogether, this evidence indicates that cortisol exerts paracrine roles in the zebrafish testicular function and spermatogenesis, highlighting its effects on spermatogonial differentiation, meiosis, and spermiogenesis.

Gilead Sciences Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. for some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. the largest viremic populations were in Egypt, with 6358000 cases in 2008 and Brazil with 2106000 cases in 2007. the age distribution of cases differed between countries. in most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level. Arud Ctr Addict Med, CH-8005 Zurich, Switzerland Univ Leipzig, D-04109 Leipzig, Germany Odense Univ Hosp, Dept Infect Dis, DK-5000 Odense, Denmark Univ Libre Brussels, Erasme Univ Hosp, Brussels, Belgium Univ Fed Rio de Janeiro, Dept Gastroenterol, Rio de Janeiro, Brazil Hop Henri Mondor, Dept Sante Publ, F-94010 Creteil, France Hosp Santa Maria, Ctr Hosp Lisboa Norte, Dept Gastroenterol, Lisbon, Portugal Univ Toronto, Toronto Gen Hosp, Univ Hlth Network, Toronto, ON M5G 1L7, Canada Nottingham Univ Hosp NHS Trust, Nottingham, England Biomed Res Unit, Nottingham, England Inst Clin & Expt Med, Dept Hepatogastroenterol, Prague, Czech Republic Ege Univ, Izmir, Turkey Ankara Univ, TR-06100 Ankara, Turkey Osped Cantonale, Dept Gastroenterol, Bellinzona, Switzerland Univ Montreal, Dept Med, Liver Unit, Montreal, PQ H3C 3J7, Canada Adv Tech Hlth Serv Res TAISS, Madrid, Spain Hosp Valle de Hebron, CIBERehd, Barcelona, Spain Hosp Santo Antonio Capuchos, Dept Gastroenterol, Ctr Hosp Lisboa Cent, Lisbon, Portugal Hosp Puerta Hierro, Madrid, Spain Univ Fed Rio Grande do Sul, Hosp Clin, Porto Alegre, RS, Brazil Region Hosp Hovedstaden, Region Hovedstaden, Denmark Univ Fed Rio de Janeiro, Dept Clin Med, Rio de Janeiro, Brazil Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany German Liver Fdn, Hannover, Germany Univ Plymouth, Peninsula Schools Med & Dent, Plymouth PL4 8AA, Devon, England Univ New S Wales, Kirby Inst, Sydney, NSW, Australia Cairo Univ, Cairo, Egypt Orebro Univ Hosp, Dept Infect Dis, Orebro, Sweden Univ Orebro, Sch Hlth & Med Sci, SE-70182 Orebro, Sweden Ain Shams Univ, Cairo, Egypt Dokuz Eylul Univ, Izmir, Turkey Ctr Dis Anal CDA, Louisville, CO USA Karolinska Inst, Infect Dis Unit, Dept Med Huddinge, Stockholm, Sweden Exigo Consultores, Alhos Vedros, Portugal Universidade Federal de São Paulo, Div Gastroenterol, São Paulo, Brazil Universidade Federal de São Paulo, Div Infect Dis, São Paulo, Brazil Hosp Carlos III, CIBERehd, Madrid, Spain Univ Copenhagen, Copenhagen, Denmark Direccao Geral Saude, Lisbon, Portugal Univ Estadual Campinas, Fac Ciencias Med, UNICAMP,Dept Clin Med, Grp Estudo Hepatites,Disciplina Doencas Infeccios, São Paulo, Brazil Wilhelminenspital Stadt Wien, Dept Internal Med 4, Vienna, Austria Univ São Paulo, Sch Med, Div Gastroenterol & Hepatol, São Paulo, Brazil Hop Henri Mondor, Serv Hepatogastroenterol, F-94010 Creteil, France Med Univ Vienna, Dept Internal Med 3, Div Gastroenterol & Hepatol, Vienna, Austria Masaryk Univ, Univ Hosp Brno, Clin Infect Dis, Brno, Czech Republic Ankara Univ, Dept Gastroenterol, Sch Med, TR-06100 Ankara, Turkey Univ Manitoba, Dept Internal Med, Sect Hepatol, Winnipeg, MB, Canada Hlth Sci Ctr, Viral Hepatitis Invest Unit, Winnipeg, MB, Canada European Liver Patients Assoc, St Truiden, Belgium Istanbul Univ, Istanbul, Turkey Univ British Columbia, British Columbia Ctr Dis Control, Vancouver, BC V5Z 1M9, Canada Aalborg Univ Hosp, Dept Med Gastroenterol, Aalborg, Denmark Aalborg Univ Hosp, Sect Mol Diagnost, Aalborg, Denmark Katholieke Univ Leuven, Univ Hosp Leuven, Louvain, Belgium Univ Western Ontario, Div Gastroenterol, London, ON, Canada Univ Dusseldorf, Dusseldorf, Germany Univ São Paulo, Sch Med, São Paulo, Brazil Univ Zurich Hosp, Swiss HPB Hepatopancreatobiliary Ctr, CH-8091 Zurich, Switzerland Univ Zurich Hosp, Dept Gastroenterol & Hepatol, CH-8091 Zurich, Switzerland Univ Calgary, Liver Unit, Div Gastroenterol & Hepatol, Calgary, AB, Canada Univ Hosp, Div Gastroenterol & Hepatol, Geneva, Switzerland Univ Hosp, Div Clin Pathol, Geneva, Switzerland Natl Inst Publ Hlth, Natl Reference Lab Hepatitis, Prague, Czech Republic Univ Southhampton, Southampton, England Dalhousie Univ, Dept Med, Halifax, NS, Canada Dalhousie Univ, Dept Surg, Halifax, NS B3H 4H2, Canada Capital Dist Hlth Author, Serv Hepatol, Queen Elizabeth II Hlth Sci Ctr, Halifax, NS, Canada Univ British Columbia, Dept Gastroenterol, Vancouver, BC V5Z 1M9, Canada Assembleia Republ, Lisbon, Portugal Alfred Hosp, Melbourne, Vic, Australia Monash Univ, Melbourne, Vic 3004, Australia UCL, UCL Inst Liver & Digest Hlth, Div Med, London, England Ctr Hosp Porto, Dept Infect Dis, Oporto, Portugal JW Goethe Univ Hosp, Frankfurt, Germany Cantonal Hosp St Gallen, Div Gastroenterol & Hepatol, St Gallen, Switzerland Egyptian Liver Res Inst & Hosp ELRIAH, Dakahliah, Egypt Monash Hlth, Melbourne, Vic, Australia Catholic Univ Louvain, Clin Univ St Luc, Brussels, Belgium Med Univ Graz, Dept Internal Med, Div Gastroenterol & Hepatol, Graz, Austria St Vincents Hosp, Dept Gastroenterol, Melbourne, Vic, Australia Univ Melbourne, Melbourne, Vic, Australia Charles Univ Prague, Dept Internal Med, Fac Med 1, Prague, Czech Republic Cent Mil Hosp, Prague, Czech Republic Deutsch Leberhilfe eV, Cologne, Germany Ghent Univ Hosp, Ghent, Belgium Univ Ghent, B-9000 Ghent, Belgium Hasselt Univ, Dept Hlth Econ & Patient Safety, Diepenbeek, Belgium Med Univ Innsbruck, A-6020 Innsbruck, Austria Natl Liver Inst, Menoufia, Egypt Copenhagen Univ Hosp, Hvidovre, Denmark Univ New S Wales, St George Hosp Clin Sch Med, Sydney, NSW, Australia Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia Univ Antwerp, B-2020 Antwerp, Belgium Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden Karolinska Univ Hosp, Dept Gastroenterol & Hepatol Infect Dis, Stockholm, Sweden Universidade Federal de São Paulo, Div Gastroenterol, São Paulo, Brazil Universidade Federal de São Paulo, Div Infect Dis, São Paulo, Brazil Web of Science

Gilead Sciences The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. the largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical. Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-30625 Hannover, Germany German Liver Fdn, Hannover, Germany Orebro Univ Hosp, Dept Infect Dis, Orebro, Sweden Univ Orebro, Sch Hlth & Med Sci, SE-70182 Orebro, Sweden Hosp Valle de Hebron, CIBERehd, Barcelona, Spain UCL, Div Med, UCL Inst Liver & Digest Hlth, London, England Inst Clin & Expt Med, Dept Hepatogastroenterol, Prague, Czech Republic Cairo Univ, Cairo, Egypt Ankara Univ, TR-06100 Ankara, Turkey Ghent Univ Hosp, Ghent, Belgium Wilhelminenspital Stadt Wien, Dept Internal Med 4, Vienna, Austria Ege Univ, Izmir, Turkey Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden Karolinska Univ Hosp, Dept Gastroenterol & Hepatol Infect Dis, Stockholm, Sweden Univ Leipzig, D-04109 Leipzig, Germany Osped Cantonale, Dept Gastroenterol, Bellinzona, Switzerland Univ Montreal, Dept Med, Liver Unit, Montreal, PQ H3C 3J7, Canada Adv Tech Hlth Serv Res TAISS, Madrid, Spain Fed Univ State Rio de Janeiro, Dept Gastroenterol, Rio de Janeiro, Brazil Arud Ctr Addict Med, Zurich, Switzerland Hosp Santo Antonio Capuchos, Ctr Hosp Lisboa Cent, Dept Gastroenterol, Lisbon, Portugal Hosp Puerta Hierro, Madrid, Spain Univ Fed Rio Grande do Sul, Hosp Clin, Porto Alegre, RS, Brazil Odense Univ Hosp, Dept Infect Dis, DK-5000 Odense, Denmark Region Hosp Hovedstaden, Region Hovedstaden, Denmark Univ Fed Rio de Janeiro, Dept Clin Med, Rio de Janeiro, Brazil Univ Plymouth, Peninsula Sch Med & Dent, Plymouth PL4 8AA, Devon, England Univ New S Wales, Kirby Inst, Sydney, NSW, Australia Ain Shams Univ, Cairo, Egypt Dokuz Eylul Univ, Izmir, Turkey Ctr Dis Anal CDA, Louisville, CO USA Karolinska Inst, Dept Med Huddinge, Karolinska Univ Hosp, Infect Dis Unit, Stockholm, Sweden Exigo Consultores, Alhos Vedros, Portugal Universidade Federal de São Paulo, Div Gastroenterol, São Paulo, Brazil Universidade Federal de São Paulo, Div Infect Dis, São Paulo, Brazil Hosp Carlos III, CIBERehd, Madrid, Spain Univ Copenhagen, Copenhagen, Denmark Direccao Geral Saude, Lisbon, Portugal Univ Estadual Campinas, Fac Ciencias Med, Disciplina Doencas Infecciosas, Grp Estudo Hepatites,Dept Clin Med, São Paulo, Brazil Univ São Paulo, Sch Med, Div Gastroenterol & Hepatol, São Paulo, Brazil Hop Henri Mondor, Serv Hepatogastroenterol, F-94010 Creteil, France Med Univ Vienna, Div Gastroenterol & Hepatol, Dept Internal Med 3, Vienna, Austria Masaryk Univ, Clin Infect Dis, Univ Hosp Brno, Brno, Czech Republic Ankara Univ, Dept Gastroenterol, Sch Med, TR-06100 Ankara, Turkey Univ Manitoba, Dept Internal Med, Sect Hepatol, Winnipeg, MB, Canada Hlth Sci Ctr, Viral Hepatitis Invest Unit, Winnipeg, MB, Canada European Liver Patients Assoc, St Truiden, Belgium Istanbul Univ, Istanbul, Turkey Univ British Columbia, British Columbia Ctr Dis Control, Vancouver, BC V5Z 1M9, Canada Aalborg Univ Hosp, Dept Med Gastroenterol, Aalborg, Denmark Aalborg Univ Hosp, Sect Mol Diagnost, Aalborg, Denmark Katholieke Univ Leuven, Univ Hosp Leuven, Louvain, Belgium Univ Western Ontario, Div Gastroenterol, London, ON, Canada Univ Dusseldorf, Dusseldorf, Germany Univ São Paulo, Sch Med, São Paulo, Brazil Univ Libre Brussels, Erasme Univ Hosp, Brussels, Belgium Univ Zurich Hosp, Swiss HPB Hepatopancreatobiliary Ctr, CH-8091 Zurich, Switzerland Univ Zurich Hosp, Dept Gastroenterol & Hepatol, CH-8091 Zurich, Switzerland Univ Calgary, Div Gastroenterol & Hepatol, Liver Unit, Calgary, AB, Canada Natl Inst Publ Hlth, Natl Reference Lab Hepatitis, Prague, Czech Republic Univ Southhampton, Southampton, England Dalhousie Univ & Hepatol Serv, Queen Elizabeth II Hlth Sci Ctr, Capital Dist Hlth Author, Dept Med, Halifax, NS, Canada Dalhousie Univ & Hepatol Serv, Queen Elizabeth II Hlth Sci Ctr, Capital Dist Hlth Author, Dept Surg, Halifax, NS, Canada Univ British Columbia, Dept Gastroenterol, Vancouver, BC V5Z 1M9, Canada Assembleia Republ, Lisbon, Portugal Alfred Hosp, Melbourne, Vic, Australia Monash Univ, Melbourne, Vic 3004, Australia Hop Henri Mondor, Dept Sante Publ, F-94010 Creteil, France Nottingham Univ Hosp NHS Trust, Nottingham, England Biomed Res Unit, Nottingham, England Ctr Hosp Porto, Dept Infect Dis, Oporto, Portugal JW Goethe Univ Hosp, Frankfurt, Germany Cantonal Hosp St Gallen, Div Gastroenterol & Hepatol, St Gallen, Switzerland Univ Toronto, Toronto Gen Hosp, Univ Hlth Network, Toronto, ON M5G 1L7, Canada Egyptian Liver Res Inst & Hosp ELRIAH, Dakahliah, Egypt Catholic Univ Louvain, Clin Univ St Luc, Brussels, Belgium Med Univ Graz, Div Gastroenterol & Hepatol, Dept Internal Med, Graz, Austria St Vincents Hosp, Dept Gastroenterol, Melbourne, Vic, Australia Univ Melbourne, Melbourne, Vic, Australia Charles Univ Prague, Dept Internal Med, Fac Med 1, Prague, Czech Republic Cent Mil Hosp, Prague, Czech Republic Univ Antwerp, B-2020 Antwerp, Belgium Deutsch Leberhilfe eV, Cologne, Germany Univ Ghent, Dept Hlth Econ & Patient Safety, B-9000 Ghent, Belgium Hasselt Univ, Diepenbeek, Belgium Med Univ Innsbruck, A-6020 Innsbruck, Austria Natl Liver Inst, Menoufia, Egypt Copenhagen Univ Hosp, Hvidovre, Denmark Univ New S Wales, St George Hosp Clin Sch Med, Sydney, NSW, Australia Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia Univ Hosp, Div Gastroenterol & Hepatol, Geneva, Switzerland Univ Hosp, Div Clin Pathol, Geneva, Switzerland Monash Hlth, Melbourne, Vic, Australia Division of Gastroenterology, Federal University of São Paulo, São Paulo, Brazil Division of Infectious Disease, Federal University of São Paulo, São Paulo, Brazil Web of Science

Made available in DSpace on 2015-03-18T15:55:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-11-25Bitstream added on 2015-03-18T16:28:34Z : No. of bitstreams: 1 WOS000346520700001.pdf: 205186 bytes, checksum: c29e39dcb1d87ab0b78ebf2affc7a14b (MD5) Background: Rheumatic diseases in children are associated with significant morbidity and poor health-related quality of life (HRQOL). There is no health-related quality of life (HRQOL) scale available specifically for children with less common rheumatic diseases. These diseases share several features with systemic lupus erythematosus (SLE) such as their chronic episodic nature, multi-systemic involvement, and the need for immunosuppressive medications. HRQOL scale developed for pediatric SLE will likely be applicable to children with systemic inflammatory diseases.Findings: We adapted Simple Measure of Impact of Lupus Erythematosus in Youngsters (SMILEY (c)) to Simple Measure of Impact of Illness in Youngsters (SMILY (c)-Illness) and had it reviewed by pediatric rheumatologists for its appropriateness and cultural suitability. We tested SMILY (c)-Illness in patients with inflammatory rheumatic diseases and then translated it into 28 languages. Nineteen children (79% female, n= 15) and 17 parents participated. The mean age was 12 +/- 4 years, with median disease duration of 21 months (1-172 months). We translated SMILY (c)-Illness into the following 28 languages: Danish, Dutch, French (France), English (UK), German (Germany), German (Austria), German (Switzerland), Hebrew, Italian, Portuguese (Brazil), Slovene, Spanish (USA and Puerto Rico), Spanish (Spain), Spanish (Argentina), Spanish (Mexico), Spanish (Venezuela), Turkish, Afrikaans, Arabic (Saudi Arabia), Arabic (Egypt), Czech, Greek, Hindi, Hungarian, Japanese, Romanian, Serbian and Xhosa.Conclusion: SMILY (c)-Illness is a brief, easy to administer and score HRQOL scale for children with systemic rheumatic diseases. It is suitable for use across different age groups and literacy levels. SMILY (c)-Illness with its available translations may be used as useful adjuncts to clinical practice and research. Rutgers State Univ, Robert Wood Johnson Med Sch, New Brunswick, NJ 08903 USA Rutgers State Univ, Child Hlth Inst New Jersey, New Brunswick, NJ 08901 USA Hosp Special Surg, New York, NY 10021 USA Univ Michigan, Ann Arbor, MI 48109 USA Red Cross War Mem Childrens Hosp, Cape Town, South Africa Ain Shams Univ, Pediat Allergy Immunol & Rheumatol Unit, Cairo, Egypt Ain Shams Univ, Pediat Rheumatol Pediat Allergy Immunol & Rheum, Cairo, Egypt King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia Charles Univ Prague, Prague, Czech Republic Gen Univ Hosp, Prague, Czech Republic Univ Hosp Motol, Dept Pediat, Prague, Czech Republic Aarhus Univ, Hosp Skejby, Aarhus, Denmark Rigshosp, Juliane Marie Ctr, DK-2100 Copenhagen, Denmark Univ Med Ctr, Dept Pediat Immunol, Utrecht, Netherlands Wilhelmina Childrens Hosp, Utrecht, Netherlands Great Ormond St Hosp Sick Children, Children NHS Fdn Trust, Renal Unit, London, England Lyon Univ, Hosp Civils Lyon, Rheumatol & Dermatol Dept, Lyon, France Med Univ Innsbruck, A-6020 Innsbruck, Austria Prim Univ Doz, Bregenz, Austria Hamburg Ctr Pediat & Adolescence Rheumatol, Hamburg, Germany Asklepios Clin Sankt, Augustin, Germany Univ Zurich, Childrens Hosp, Zurich, Switzerland Aristotle Univ Thessaloniki, Pediat Immunol & Rheumatol Referral Ctr, GR-54006 Thessaloniki, Greece Israel Meir Hosp, Kefar Sava, Israel Sanjay Gandhi Postgrad Inst Med Sci, Lucknow, Uttar Pradesh, India Semmelweis Univ, H-1085 Budapest, Hungary Anna Meyer Hosp, Florence, Italy Univ Siena, Res Ctr System Autoimmune & Autoinflammatory Dis, I-53100 Siena, Italy Univ Florence, Florence, Italy Osped Pediat Bambino Gesu, IRCCS, Pediat Rheumatol Unit, Rome, Italy Univ Genoa Pediat II Reumatol, Ist G Gaslini EULAR, Ctr Excellence Rheumatol, Genoa, Italy Univ Cattolica Sacro Cuore, Inst Pediat, Rome, Italy Univ Padua, Dept Pediat, Pediat Rheumatol Unit, Padua, Italy Yokohama City Univ, Sch Med, Yokohama, Kanagawa 232, Japan Univ Estadual Paulista, UNESP, Botucatu, SP, Brazil Univ Fed Sao Paulo, Dept Pediat, Sao Paulo, Brazil Univ Estadual Campinas, Dept Med, Campinas, SP, Brazil Univ Fed Rio de Janeiro, Dept Pediat, Rio De Janeiro, Brazil Univ Estado do, Adolescent Hlth Care Unit, Div Pediat Rheumatol, Rio De Janeiro, Brazil Univ Sao Paulo, Fac Med, Childrens Inst, Dept Pediat,Pediat Rheumatol Unit, Sao Paulo, Brazil Childrens Inst, Pediat Rheumatol Unit, Sao Paulo, Brazil Clin Pediat I, Cluj Napoca, Romania Inst Rheumatol, Belgrade, Serbia Univ Childrens Hosp, Univ Med Ctr Ljubljana, Ljubljana, Slovenia Head Rheumatol Hosp Pedro Elizalde, Buenos Aires, DF, Argentina Hosp Gen Mexico City, Mexico City, DF, Mexico Hosp Infantil Mexico Fed Gomez, Mexico City, DF, Mexico Hosp San Juan Dios, Barcelona, Spain Hosp Univ Valle Hebron, Barcelona, Spain Mt Sinai Med Ctr, New York, NY 10029 USA Mt Sinai Med Ctr, Miami Beach, FL 33140 USA Complejo Hosp Univ Ruiz & Paez, Bolivar, Venezuela Hacettepe Univ, Dept Pediat, Ankara, Turkey Istanbul Univ, Cerrahpasa Med Sch, Istanbul, Turkey FMF Arthrit Vasculitis & Orphan Dis Res Ctr, Inst Hlth Sci, Ankara, Turkey Univ Calgary, Dept Pediat, Alberta Childrens Hosp, Res Inst, Calgary, AB T2N 1N4, Canada Univ Estadual Paulista, UNESP, Botucatu, SP, Brazil

Gilead Sciences The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. in addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing. Ctr Dis Anal, Louisville, CO 80027 USA Natl Liver Inst, Menoufia, Egypt JW Goethe Univ Hosp, Frankfurt, Germany Univ Calgary, Liver Unit, Div Gastroenterol & Hepatol, Calgary, AB, Canada Ankara Univ, Dept Gastroenterol, Sch Med, TR-06100 Ankara, Turkey Hosp Santo Antonio Capuchos, Dept Gastroenterol, Ctr Hosp Lisboa Cent, Lisbon, Portugal Med Univ Innsbruck, A-6020 Innsbruck, Austria Univ São Paulo, Sch Med, São Paulo, Brazil Hop Henri Mondor, Serv Hepatogastroenterol, F-94010 Creteil, France Adv Tech Hlth Serv Res TAISS, Madrid, Spain Ege Univ, Izmir, Turkey Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden Karolinska Univ Hosp, Dept Gastroenterol & Hepatol Infect Dis, Stockholm, Sweden Ankara Univ, TR-06100 Ankara, Turkey Univ Leipzig, D-04109 Leipzig, Germany Osped Cantonale, Dept Gastroenterol, Bellinzona, Switzerland Univ Montreal, Dept Med, Liver Unit, Montreal, PQ H3C 3J7, Canada Fed Univ State Rio de Janeiro, Dept Gastroenterol, Rio de Janeiro, Brazil Arud Ctr Addict Med, Zurich, Switzerland Hosp Valle de Hebron, CIBERehd, Barcelona, Spain Hosp Puerta Hierro, Madrid, Spain Univ Fed Rio Grande do Sul, Hosp Clin, Porto Alegre, RS, Brazil Odense Univ Hosp, Dept Infect Dis, DK-5000 Odense, Denmark Reg Hosp Hovedstaden, Copenhagen, Denmark Univ Fed Rio de Janeiro, Dept Clin Med, Rio de Janeiro, Brazil Univ Plymouth, Peninsula Sch Med & Dent, Plymouth PL4 8AA, Devon, England Univ New S Wales, Kirby Inst, Sydney, NSW, Australia Cairo Univ, Cairo, Egypt Orebro Univ Hosp, Dept Infect Dis, Orebro, Sweden Univ Orebro, Sch Hlth & Med Sci, SE-70182 Orebro, Sweden Ain Shams Univ, Cairo, Egypt Dokuz Eylul Univ, Izmir, Turkey Karolinska Inst, Karolinska Univ Hosp, Dept Med Huddinge, Infect Dis Unit, Stockholm, Sweden Exigo Consultores, Alhos Vedros, Portugal Universidade Federal de São Paulo, Div Gastroenterol, São Paulo, Brazil Universidade Federal de São Paulo, Div Infect Dis, São Paulo, Brazil Inst Clin & Expt Med, Dept Hepatogastroenterol, Prague, Czech Republic Hosp Carlos III, CIBERehd, Madrid, Spain Univ Copenhagen, Copenhagen, Denmark Direccao Geral Saude, Lisbon, Portugal Univ Estadual Campinas, Disciplina Doencas Infecciosas, Dept Clin Med, Grp Estudo Hepatites,Fac Ciencias Med,UNICAMP, São Paulo, Brazil Wilhelminenspital Stadt Wien, Dept Internal Med 4, Vienna, Austria Univ São Paulo, Sch Med, Div Gastroenterol & Hepatol, São Paulo, Brazil Med Univ Vienna, Div Gastroenterol & Hepatol, Dept Internal Med 3, Vienna, Austria Masaryk Univ, Univ Hosp Brno, Clin Infect Dis, Brno, Czech Republic Univ Manitoba, Dept Internal Med, Sect Hepatol, Winnipeg, MB, Canada Hlth Sci Ctr, Viral Hepatitis Invest Unit, Winnipeg, MB, Canada European Liver Patients Assoc, St Truiden, Belgium Istanbul Univ, Istanbul, Turkey Univ British Columbia, British Columbia Ctr Dis Control, Vancouver, BC V5Z 1M9, Canada Aalborg Univ Hosp, Dept Med Gastroenterol, Aalborg, Denmark Aalborg Univ Hosp, Sect Mol Diagnost, Aalborg, Denmark Katholieke Univ Leuven, Univ Hosp Leuven, Louvain, Belgium Hosp Santa Maria, Dept Gastroenterol, Ctr Hosp Lisboa Norte, Lisbon, Portugal Univ Western Ontario, Div Gastroenterol, London, ON, Canada Univ Dusseldorf, Dusseldorf, Germany Univ Libre Brussels, Erasme Univ Hosp, Brussels, Belgium Univ Hosp, Div Gastroenterol & Hepatol, Geneva, Switzerland Univ Hosp, Div Clin Pathol, Geneva, Switzerland Natl Inst Publ Hlth, Natl Reference Lab Hepatitis, Prague, Czech Republic Univ Southhampton, Southampton, England Dalhousie Univ & Hepatol Serv, Capital Dist Hlth Author, Queen Elizabeth II Hlth Sci Ctr, Dept Med, Halifax, NS, Canada Dalhousie Univ & Hepatol Serv, Capital Dist Hlth Author, Queen Elizabeth II Hlth Sci Ctr, Dept Surg, Halifax, NS, Canada Univ British Columbia, Dept Gastroenterol, Vancouver, BC V5Z 1M9, Canada Assembleia Republ, Lisbon, Portugal Alfred Hosp, Melbourne, Vic, Australia Monash Univ, Melbourne, Vic 3004, Australia UCL, Div Med, UCL Inst Liver & Digest Hlth, London, England Hop Henri Mondor, Dept Sante Publ, F-94010 Creteil, France Nottingham Univ Hosp NHS Trust, Nottingham, England Biomed Res Unit, Nottingham, England Ctr Hosp Porto, Dept Infect Dis, Oporto, Portugal Cantonal Hosp St Gallen, Div Gastroenterol & Hepatol, St Gallen, Switzerland Univ Toronto, Toronto Gen Hosp, Univ Hlth Network, Toronto, ON M5G 1L7, Canada Egyptian Liver Res Inst & Hosp, Dakahliah, Egypt Monash Hlth, Melbourne, Vic, Australia Catholic Univ Louvain, Clin Univ St Luc, Brussels, Belgium Med Univ Graz, Div Gastroenterol & Hepatol, Dept Internal Med, Graz, Austria St Vincents Hosp, Dept Gastroenterol, Melbourne, Vic, Australia Univ Melbourne, Melbourne, Vic, Australia Charles Univ Prague, Dept Internal Med, Fac Med 1, Prague, Czech Republic Cent Mil Hosp, Prague, Czech Republic Univ Antwerp, B-2020 Antwerp, Belgium Deutsch Leberhilfe eV, Cologne, Germany Ghent Univ Hosp, Ghent, Belgium Univ Ghent, Belgium Hasselt Univ, Dept Hlth Econ & Patient Safety, Diepenbeek, Belgium Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany Copenhagen Univ Hosp, Hvidovre, Denmark Univ New S Wales, St George Hosp Clin Sch Med, Sydney, NSW, Australia Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia Univ Zurich Hosp, Swiss HPB Hepatopancreatobiliary Ctr, CH-8091 Zurich, Switzerland Univ Zurich Hosp, Dept Gastroenterol & Hepatol, CH-8091 Zurich, Switzerland Universidade Federal de São Paulo, Div Gastroenterol, São Paulo, Brazil Universidade Federal de São Paulo, Div Infect Dis, São Paulo, Brazil Web of Science

To access publisher's full text version of this article click on the hyperlink at the bottom of the page Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped using the Immunochip. We identified 12 genome-wide significant associations outside the human leukocyte antigen (HLA) complex, 9 of which were new, increasing the number of known PSC risk loci to 16. Despite comorbidity with inflammatory bowel disease (IBD) in 72% of the cases, 6 of the 12 loci showed significantly stronger association with PSC than with IBD, suggesting overlapping yet distinct genetic architectures for these two diseases. We incorporated association statistics from 7 diseases clinically occurring with PSC in the analysis and found suggestive evidence for 33 additional pleiotropic PSC risk loci. Together with network analyses, these findings add to the genetic risk map of PSC and expand on the relationship between PSC and other immune-mediated diseases. Norwegian PSC Research Center German Ministry of Education and Research through the National Genome Research Network 01GS0809-GP7 Deutsche Forschungsgemeinschaft FR 2821/2-1 Integrated Research and Treatment Center-Transplantation 01EO0802 PopGen Biobank Wellcome Trust 098051 info:eu-repo/grantAgreement/EC/FP7/262055

German Federal Ministry of Education and Research A significant knowledge gap exists concerning the geographical distribution of nontuberculous mycobacteria (NTM) isolation worldwide.To provide a snapshot of NTM species distribution, global partners in the NTM-Network European Trials Group (NET) framework (www.ntm-net.org), a branch of the Tuberculosis Network European Trials Group (TB-NET), provided identification results of the total number of patients in 2008 in whom NTM were isolated from pulmonary samples. From these data, we visualised the relative distribution of the different NTM found per continent and per country.We received species identification data for 20182 patients, from 62 laboratories in 30 countries across six continents. 91 different NTM species were isolated. Mycobacterium avium complex (MAC) bacteria predominated in most countries, followed by M. gordonae and M. xenopi. Important differences in geographical distribution of MAC species as well as M. xenopi, M. kansasii and rapid-growing mycobacteria were observed.This snapshot demonstrates that the species distribution among NTM isolates from pulmonary specimens in the year 2008 differed by continent and differed by country within these continents. These differences in species distribution may partly determine the frequency and manifestations of pulmonary NTM disease in each geographical location. Radboud Univ Nijmegen, Med Ctr, Dept Pulm Dis, NL-6500 HB Nijmegen, Netherlands Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, NL-6500 HB Nijmegen, Netherlands Amiens Teaching Hosp, Dept Resp Dis, Amiens, France Karolinska Inst, Dept Clin Microbiol, Stockholm, Sweden Hop Purpan, Lab Cent Microbiol, Toulouse, France CHU Nantes, Inst Biol, Serv Bacteriol Hyg, F-44035 Nantes 01, France Natl Hlth Lab Serv, Braamfontein, South Africa Univ Hosp Getafe, Dept Microbiol, Getafe, Spain Aurum Inst Hlth Res, Johannesburg, South Africa Adolfo Lutz Inst, Secao Bacteriol, Setor Micobacterias, São Paulo, Brazil Hosp Clin San Carlos, Dept Clin Microbiol, Madrid, Spain Hosp Univ Puerta de Hierro, Dept Microbiol, Madrid, Spain Natl Jewish Hlth, Div Mycobacterial & Resp Infect, Denver, CO USA Hosp Univ Princesa, Dept Microbiol, Madrid, Spain UK Hlth Protect Agcy, Natl Mycobacterium Reference Lab, London, England IIS Fdn Jimenez Diaz, Dept Clin Microbiology, Madrid, Spain Sci Inst Publ Hlth, Natl Reference Ctr TB & Mycobacteria, Brussels, Belgium Statens Serum Inst, Int Reference Lab Mycobacteriol, DK-2300 Copenhagen, Denmark St James Hosp, Dublin 8, Ireland Univ Dublin Trinity Coll, Dublin 2, Ireland Hosp Ramon & Cajal, E-28034 Madrid, Spain Hosp Univ Principe Asturias, Madrid, Spain Asklepios Facbkliniken, Supranat Reference Lab, Inst Microbiol & Lab Med, Gauting, Germany Natl Taiwan Univ Hosp, Dept Lab Med, Taipei, Taiwan Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan Austrian Agcy Hlth & Food Safety, Vienna, Austria Univ Warsaw, Fac Biol, Inst Microbiol, Dept Appl Microbiol, Warsaw, Poland Ontario Minist Hlth & Long Term Care, Publ Hlth Labs Branch, Toronto, ON, Canada Univ Zagreb Med Sch, Univ Hosp Ctr, Dept Resp Dis, Zagreb, Croatia Univ Witwatersrand, Clin HIV Res Unit, Johannesburg, South Africa St Jamess Hosp Dublin, Dublin, Ireland Sungkyunkwan Univ Sch Med, Samsung Med Ctr, Dept Med, Div Pulm & Crit Care Med, Seoul, South Korea Univ Hosp Freiburg, Ctr Infect Dis & Travel Med, Freiburg, Germany Universidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, Disciplina Microbiol, São Paulo, Brazil Adm Reg Saude Lisboa & Vale Tejo, Dept Publ Hlth, Publ Hlth Lab Mycobacteriol TB, Lisbon, Portugal Norwegian Inst Publ Hlth, Div Infect Dis Control, Oslo, Norway Univ Toronto, Univ Hlth Network, Joint Div Respirol, Toronto, ON, Canada Univ Toronto, Mt Sinai Hosp, Dept Med, Toronto, ON M5G 1X5, Canada Univ Victor Segalen Bordeaux, Lab Bacteriol, Bordeaux, France Guys & St Thomas NHS Fdn Trust, Dept Resp Med, London, England Koranyi Natl Inst TB & Pulmonol, Budapest, Hungary Hosp Dr Antonio Cetrangolo, Programa Control TB Prov Buenos Aires, Lab Referencia, Buenos Aires, Brazil Fukujuji Hosp, Japan AntiTB Assoc, Tokyo, Japan Sotiria Chest Dis Hosp, Natl Mycobacteria Reference Lab, Athens, Greece Hosp 12 Octubre, Dept Microbiol, E-28041 Madrid, Spain Hosp Severo Ochoa, Madrid, Spain United Hosp, Reg Reference Mycobacteria Lab, Ancona, Italy Natl Inst TB Resp Dis & Chest Surg, Vysne Hagy, Slovakia Inst Pasteur Guadeloupe, Unite TB & Mycobacteries, WHO Supranat TB Reference Lab, Abymes, Guadeloupe Natl Reference Ctr Mycobacteria, Borstel, Germany Hosp Gregorio Maranon, Serv Microbiol Clin & Enfermedades Infecciosas, Madrid, Spain Gen Directorate Hlth Lisbon, Amadora, Portugal Lung Dis Ctr Venda Nova, Amadora, Portugal Univ Witwatersrand, Johannesburg, South Africa Refik Saydam Natl Publ Hlth Agcy, Natl TB Reference Lab, Ankara, Turkey Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands Koranyi Natl Inst TB & Resp Med, Budapest, Hungary Greenslopes Private Hosp, Gallipoli Med Res Ctr, Brisbane, Qld, Australia Hosp Val dHebron, Barcelona, Spain Ist Sci San Raffaele, Emerging Bacterial Pathogens Unit, I-20132 Milan, Italy Natl Jewish Hlth, Adv Diagnost Labs, Dept Mycobacteriol, Denver, CO USA Univ Calgary, Prov Lab Publ Hlth, Calgary, AB, Canada Natl Inst Hlth & Welf, Epidemiol Surveillance & Response Unit, Dept Infect Dis Surveillance & Control, Helsinki, Finland Med Univ Warsaw, Dept Internal Med Pneumol & Allergol, Warsaw, Poland Oregon Hlth & Sci Univ, Div Infect Dis Publ Hlth & Prevent Med, Portland, OR 97201 USA Univ Freiburg, Dept Internal Med Infect Dis 2, D-79106 Freiburg, Germany Universidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, Disciplina Microbiol, São Paulo, Brazil German Federal Ministry of Education and Research: BMBF 01 EO 0803 Web of Science

Made available in DSpace on 2013-09-27T14:53:48Z (GMT). No. of bitstreams: 1 WOS000273204800008.pdf: 480548 bytes, checksum: e09bb5695ebf579e0f4a64c3302fd33a (MD5) Previous issue date: 2009-01-01 Made available in DSpace on 2013-09-30T18:08:54Z (GMT). No. of bitstreams: 1 WOS000273204800008.pdf: 480548 bytes, checksum: e09bb5695ebf579e0f4a64c3302fd33a (MD5) Previous issue date: 2009-01-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:22:45Z No. of bitstreams: 1 WOS000273204800008.pdf: 480548 bytes, checksum: e09bb5695ebf579e0f4a64c3302fd33a (MD5) Made available in DSpace on 2014-05-20T13:22:45Z (GMT). No. of bitstreams: 1 WOS000273204800008.pdf: 480548 bytes, checksum: e09bb5695ebf579e0f4a64c3302fd33a (MD5) Previous issue date: 2009-01-01 In this paper, a methodology is proposed for the geometric refinement of laser scanning building roof contours using high-resolution aerial images and Markov Random Field (MRF) models. The proposed methodology takes for granted that the 3D description of each building roof reconstructed from the laser scanning data (i.e., a polyhedron) is topologically correct and that it is only necessary to improve its accuracy. Since roof ridges are accurately extracted from laser scanning data, our main objective is to use high-resolution aerial images to improve the accuracy of roof outlines. In order to meet this goal, the available roof contours are first projected onto the image-space. After that, the projected polygons and the straight lines extracted from the image are used to establish an MRF description, which is based on relations ( relative length, proximity, and orientation) between the two sets of straight lines. The energy function associated with the MRF is minimized by using a modified version of the brute force algorithm, resulting in the grouping of straight lines for each roof object. Finally, each grouping of straight lines is topologically reconstructed based on the topology of the corresponding laser scanning polygon projected onto the image-space. The preliminary results showed that the proposed methodology is promising, since most sides of the refined polygons are geometrically better than corresponding projected laser scanning straight lines. Univ Estadual Paulista, UNESP, FCT, Dept Cartog, BR-19060900 Presidente Prudente, SP, Brazil Univ Calgary, Dept Geomat Engn, Schulich Sch Engn, Calgary, AB T2N 1N4, Canada Univ Estadual Paulista, UNESP, FCT, Dept Cartog, BR-19060900 Presidente Prudente, SP, Brazil

The aim of this study was to characterize a novel human autoantibody-autoantigen system represented as cytoplasmic discrete speckles (CDS) in indirect immunofluorescence (IIF). A distinct CDS IIF pattern represented by 3-20 discrete speckles dispersed throughout the cytoplasm was identified among other cytoplasmic speckled IIF patterns. the cytoplasmic domains labelled by human anti-CDS-1 antibodies did not co-localize with endosome/lysosome markers EEA1 and LAMP-2, but showed partial co-localization with glycine-tryptophan bodies (GWB). CDS-1 sera did not react with several cellular extracts in immunoblotting and did not immunoprecipitate recombinant GW182 or EEA1 proteins. the typical CDS-1 IIF labelling pattern was abolished after delipidation of HEp-2 cells. Moreover, CDS-1 sera reacted strongly with a lipid component co-migrating with phosphatidylethanolamine (PE) in high performance thin-layer chromatography (HPTLC)-immunostaining of HEp-2 cell total lipid extracts. the CDS-1 major molecular targets were established by electrospray ionization-mass spectrometry (ESI-MS), HPTLC-immunostaining and chemiluminescent enzyme-linked immunosorbent assay as diacyl-PE species, containing preferentially a cis-C18 : 1 fatty acid chain at C-2 of the glycerol moiety, namely 1,2-cis-C18 : 1-PE and 1-C16 : 0-2-cis-C18 : 1-PE. the clinical association of CDS-1 sera included a variety of systemic and organ-specific autoimmune diseases but they were also observed in patients with no evidence of autoimmune disease. Universidade Federal de São Paulo, Div Rheumatol, Escola Paulista Med, BR-04023062 São Paulo, Brazil Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB, Canada UNIFESP, EPM, Dept Microbiol Imunol & Parasitol, São Paulo, Brazil Univ Texas, Dept Biol Sci, El Paso, TX 79968 USA Univ São Paulo, ICB, Dept Parasitol, São Paulo, Brazil Universidade Federal de São Paulo, Div Rheumatol, Escola Paulista Med, BR-04023062 São Paulo, Brazil UNIFESP, EPM, Dept Microbiol Imunol & Parasitol, São Paulo, Brazil Web of Science