bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic Resonance Imaging of the Rheumatic Foot According to the RAMRIS System Is Reliable
Authors: BAAN HENRIËTTE , BEZOOIJEN ROLAND , AVENARIUS JOHANNES K.A. , DUBBELDAM ROSEMARY , DROSSAERS-BAKKER WIEPKE K. , van de LAAR MARTIN A.F.J.
Published: March 2011

Objective.

In rheumatology, magnetic resonance imaging (MRI) is predominantly applied in the assessment and outcome measurement of rheumatoid arthritis (RA) in hands and wrists, leading to the development of the RAMRIS (RA-MRI-Scoring) system. It was initiated by the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT). The RAMRIS system has not been applied widely in the measurement of feet. We investigated the interreader and intrareader agreement of the RAMRIS scoring system in the assessment of feet in RA.

Methods.

Twenty-nine patients with RA who had radiological damage and/or arthritis underwent MRI. Two experienced readers independently read both complete sets. One reader read 6 random sets after the initial session, in order to assess the intrareader agreement. For evaluation of the intrareader and interreader reliability, quadratic-weighted κ scores were calculated per joint and lesion.

Results.

For the forefeet, interreader scores were excellent, ranging from 0.77 (bone edema) to 0.95 (bone erosion). Hindfoot interreader agreement scores were highest for erosion (0.90) and synovitis global score (0.88), but edema and synovial thickness agreement were also acceptable (0.83 and 0.86). Intrareader scores were on the whole slightly lower, but excellent.

Conclusion.

Reliability (interreader and intrareader agreement) in the assessment of the rheumatoid foot according to the RAMRIS method is excellent.
A New Approach to Clinical Care of Juvenile Idiopathic Arthritis: The Juvenile Arthritis Multidimensional Assessment Report
Authors: FILOCAMO GIOVANNI , CONSOLARO ALESSANDRO , SCHIAPPAPIETRA BENEDETTA , DALPRÀ SARA , LATTANZI BIANCA , MAGNI-MANZONI SILVIA , RUPERTO NICOLINO , PISTORIO ANGELA , PEDERZOLI SILVIA , CIVINO ADELE , GUSEINOVA DINARA , MASALA ESTER , VIOLA STEFANIA , MARTINI ALBERTO , RAVELLI ANGELO
Published: March 2011

Objective.

To develop and test a new multidimensional questionnaire for assessment of children with juvenile idiopathic arthritis (JIA) in standard clinical care.

Methods.

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) includes 15 parent or patient-centered measures or items that assess well-being, pain, functional status, health-related quality of life, morning stiffness, disease activity, disease status and course, joint disease, extraarticular symptoms, side effects of medications, therapeutic compliance, and satisfaction with illness outcome. The JAMAR is proposed for use as both a proxy-report and a patient self-report, with the suggested age range of 7–18 years for use as a self-report. From March 2007 to September 2009, the questionnaire was completed by the parents of 618 children with JIA in 1814 visits and by 332 children in 749 visits.

Results.

The JAMAR was found to be feasible and to possess face and content validity. All parents and children reported that the questionnaire was simple and easy to understand. Completion and scoring appeared to be quick, requiring < 15 minutes. There were very few missing data. Parents’ proxy-reported and children’s self-reported data were remarkably concordant. The JAMAR provided thorough information for the study patients about recent medical history and current health status. It performed similarly across different children’s ages and characterized the level of disease activity and disability well.

Conclusion.

The development of the JAMAR introduces a new approach in pediatric rheumatology practice. This new questionnaire may help enhance the quality of care of children with JIA.
Association Study of ITGAM, ITGAX, and CD58 Autoimmune Risk Loci in Systemic Sclerosis: Results from 2 Large European Caucasian Cohorts
Authors: COUSTET BAPTISTE , AGARWAL SANDEEP K. , GOURH PRAVITT , GUEDJ MICKAEL , MAYES MAUREEN D. , DIEUDE PHILIPPE , WIPFF JULIEN , AVOUAC JEROME , HACHULLA ERIC , DIOT ELISABETH , CRACOWSKI JEAN LUC , TIEV KIET , SIBILIA JEAN , MOUTHON LUC , FRANCES CAMILLE , AMOURA ZAHIR , CARPENTIER PATRICK , MEYER OLIVIER , KAHAN ANDRE , BOILEAU CATHERINE , ARNETT FRANK C. , ALLANORE YANNICK
Published: March 2011

Objective.

Accumulating evidence shows that shared autoimmunity is critical for the pathogenesis of many autoimmune diseases. Systemic sclerosis (SSc) belongs to the connective tissue disorders, and recent data have highlighted strong associations with autoimmunity genes shared with other autoimmune diseases. To determine whether novel risk loci associated with systemic lupus erythematosus or multiple sclerosis may confer susceptibility to SSc, we tested single-nucleotide polymorphisms (SNP) from ITGAM, ITGAX, and CD58 for associations.

Methods.

SNP harboring associations with autoimmune diseases, ITGAM rs9937837, ITGAX rs11574637, and CD58 rs12044852, were genotyped in 2 independent cohorts of European Caucasian ancestry: 1031 SSc patients and 1014 controls from France and 1038 SSc patients and 691 controls from the USA, providing a combined study population of 3774 individuals. ITGAM rs1143679 was additionally genotyped in the French cohort.

Results.

The 4 polymorphisms were in Hardy-Weinberg equilibrium in the 2 control populations, and allelic frequencies were similar to those expected in European Caucasian populations. Allelic and genotypic frequencies for these 3 SNP were found to be statistically similar in SSc patients and controls. Subphenotype analyses for subgroups having diffuse cutaneous subtype disease, specific autoantibodies, or fibrosing alveolitis did not reveal any difference between SSc patients and controls.

Conclusion.

These results obtained through 2 large cohorts of SSc patients of European Caucasian ancestry do not support the implication of ITGAM, ITGAX, and CD58 genes in the genetic susceptibility of SSc, although they were recently identified as autoimmune disease risk genes.
Interaction Between Smoking and Polymorphism in the Promoter Region of the VEGFA Gene Is Associated with Ischemic Heart Disease and Myocardial Infarction in Rheumatoid Arthritis
Authors: CHEN YING , DAWES PETER T. , PACKHAM JONATHAN C. , MATTEY DEREK L.
Published: March 2011

Objective.

To determine whether variants in the vascular endothelial growth factor A (VEGFA) gene are associated with ischemic heart disease (IHD) and/or myocardial infarction (MI) in patients with rheumatoid arthritis (RA), and whether there is evidence of a gene-smoking interaction.

Methods.

PCR-RFLP assays were used to determine the genotypes of VEGFA single-nucleotide polymorphisms (SNP) including VEGFA–2578A/C (rs699947), −460C/T (rs833061), +405C/G (rs2010963), and +936C/T (rs3025039) in 418 subjects with RA. Smoking history was obtained on each patient, and IHD and MI status was recorded. Associations with IHD/MI were assessed using contingency tables and logistic regression analyses.

Results.

Strong linkage disequilibrium was detected among VEGFA–2578, −460, and +405. SNP located in the VEGFA promoter region (−2578, −460) were found to be associated with IHD and MI, whereas +405 and +936, in the 5′-untranslated region (UTR) and 3′-UTR, respectively, were not. Haplotype analysis suggested that the A/C/G haplotype was associated with increased risk of IHD (OR 2.37, 95% CI 1.22–4.62) and MI (OR 4.10, 95% CI 1.45–11.49). Smoking was also independently associated with IHD and MI, and evidence of interaction between smoking and the VEGFA promoter SNP was found. Multivariate analyses indicated that the strongest associations with IHD and MI were due to the combined effect of the VEGFA–2578 A allele and smoking (OR 3.52 and 7.11, respectively), independent of risk factors such as age, sex, diabetes, C-reactive protein, hypercholesterolemia, and hypertension.

Conclusion.

Interaction between smoking and polymorphism in the VEGFA gene is associated with IHD and MI in patients with RA.
Are Symptoms of Late Whiplash Specific? A Comparison of SCL-90-R Symptom Profiles of Patients with Late Whiplash and Patients with Chronic Pain Due to Other Types of Trauma
Authors: RADANOV BOGDAN P. , MANNION ANNE F. , BALLINARI PIETRO
Published: March 2011

Objective.

Focusing on symptoms referred to as specific for late whiplash may contribute to misconceptions in assessment, treatment, and settlements. We compared Symptom Checklist 90-Revised (SCL-90-R) symptom profiles of patients with late whiplash and patients with chronic pain due to other types of trauma.

Methods.

We compared 156 late whiplash patients (WP group) with 54 chronic pain patients who had suffered different bodily trauma (non-WP group) with regard to the following aspects of the SCL-90-R: the Positive Symptom Total (PST); the nine SCL-90-R dimensions and additional global indices, i.e., Global Severity Index (GSI) and Positive Symptom Distress (PSD); and complaints referred to as specific for late whiplash syndrome.

Results.

The mean adjusted T score for PST was in the normal range for the WP group (T = 56.1, 95% CI 54.1–58.1) and in the pathological range for the non-WP group (T = 61.1, 95% CI 57.3–64.9). Both the WP and non-WP groups showed mean T scores in the pathological range for the dimensions “Somatization,” “Obsessive-Compulsive,” and PSD. Only the non-WP group had an average score in the pathological range for the dimensions “Depression,” “Anxiety,” and “Phobic Anxiety” and for the global indices GSI and PST. Multivariable regression controlling for gender and education level was used to identify complaints “specific for late whiplash” that were significantly associated with being in the WP group rather than the non-WP group: greater headache (OR 1.54; 95% CI 1.16, 2.03; p = 0.003) and lower emotional lability (OR 0.96; 95% CI 0.93, 0.98; p = 0.003) were the only significant variables.

Conclusion.

Late whiplash is not a chronic pain condition characterized by specific symptoms, other than greater headache.
GRAPPA Trainees Symposium 2009: A Report from the GRAPPA 2009 Annual Meeting: Table 1.
Authors: COATES LAURA C. , RITCHLIN CHRISTOPHER T.
Published: March 2011

At the 2009 annual meeting of GRAPPA (Group for Assessment of Psoriasis and Psoriatic Arthritis) in Stockholm, Sweden, 15 fellows involved in research in psoriatic disease were invited to present their work at a Trainees Symposium, which was also attended by members of the GRAPPA Faculty Committee. All of the fellows held poster sessions of their work and 4 of them gave oral presentations, including identification of soluble biomarkers for psoriatic arthritis (PsA), validation of minimal disease activity criteria for PsA, disease progression using the modified Sharp score, and discussion of a new composite disease activity score for PsA. Senior GRAPPA members also instructed the fellows on other composite scoring methods and on training videos and other GRAPPA projects to date. All of the posters and presentations from the Trainees Symposium are summarized herein.
Psoriatic Arthritis Screening and Evaluation (PASE) Questionnaire and the Role of Dermatologists: A Report from the GRAPPA 2009 Annual Meeting: Table 1.
Authors: DOMINGUEZ PATRICK , HUSNI M. ELAINE , GARG AMIT , QURESHI ABRAR A.
Published: March 2011

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis, often with a variable course that ranges from slowly progressive to rapidly destructive. Delay in diagnosis and treatment may lead to an irreversible erosive arthropathy, leading further to physical disability and deformity. The Psoriatic Arthritis Screening and Evaluation (PASE) tool was developed and validated to help dermatologists screen more effectively for PsA; recently, it has been undergoing further validation. An update on the continuing experience with the PASE questionnaire, along with a discussion of why dermatologists have a critical role in screening for PsA, was a major focus of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting at Stockholm, Sweden, in June 2009.
Association of Anti-Modified Citrullinated Vimentin with Subclinical Atherosclerosis in Early Rheumatoid Arthritis Compared with Anti-Cyclic Citrullinated Peptide
Authors: El-BARBARY AMAL M. , KASSEM ELHAM M. , El-SERGANY MERVAT A.S. , ESSA SALWA A-M. , ELTOMEY MOHAMED A.
Published: March 2011

Objective.

To investigate anti-modified citrullinated vimentin (anti-MCV) in early rheumatoid arthritis (RA), including correlation with disease activity and cardiovascular risk factors, compared with anti-cyclic citrullinated peptides (anti-CCP3).

Methods.

Anti-MCV and anti-CCP3 concentrations were measured in 100 patients with early RA and 100 healthy controls at baseline to determine sensitivity and specificity. Patients received methotrexate (MTX) 0.2 mg/kg/week plus prednisone 10 mg/day. Anti-MCV, anti-CCP3, rheumatoid factor (RF), Disease Activity Score for 28 joints (DAS-28), lipid profile, erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein assay (hsCRP), homeostasis model assessment for insulin resistance (HOMA-IR) index, tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and carotid intima-media thickness (cIMT) were measured before and after 12 months of treatment.

Results.

The sensitivity and specificity for anti-MCV antibody were 75% and 90%, respectively, and for anti-CCP3 antibody 71% and 96%. Serum anti-MCV and serum anti-CCP3 levels at baseline were positively correlated with hsCRP, IL-6, HOMA-IR index, serum RF levels (p < 0.001), and cIMT (p < 0.05). Serum anti-MCV was positively correlated with serum anti-CCP3 levels. There were significant positive correlations between the percentage of changes of anti-MCV levels versus changes in DAS-28, ESR, hsCRP, atherogenic ratios (TC/HDL-C and LDL-C/HDL-C), apolipoprotein A-I, IL-6, TNF-α, HOMA-IR index, and cIMT. These correlations were not found between changes in anti-CCP3 levels compared to clinical, laboratory, and radiological variables.

Conclusion.

Anti-MCV was as sensitive as anti-CCP3 in diagnosing early RA. Anti-MCV testing appears to be useful for monitoring associated subclinical atherosclerosis in early RA.
High Levels of Anti-Cyclic Citrullinated Peptide Autoantibodies Are Associated with Co-occurrence of Pulmonary Diseases with Rheumatoid Arthritis
Authors: AUBART FLEUR , CRESTANI BRUNO , NICAISE-ROLAND PASCALE , TUBACH FLORENCE , BOLLET CAROLINE , DAWIDOWICZ KAREN , QUINTIN EMILIE , HAYEM GILLES , PALAZZO ELISABETH , MEYER OLIVIER , CHOLLET-MARTIN SYLVIE , DIEUDÉ PHILIPPE
Published: March 2011

Objective.

To investigate whether levels of anti-cyclic citrullinated peptide antibodies (anti-CCP2) in patients with rheumatoid arthritis (RA) are associated with the co-occurrence of lung diseases.

Methods.

A total of 252 RA patients were included in a cross-sectional study. Pulmonary disease was confirmed by high-resolution chest computed tomography scan. Circulating anti-CCP2 were quantified using ELISA. Multivariate logistic regression was conducted to identify independent risk factors for lung disease.

Results.

Male sex (OR 3.29, 95% CI 1.59–6.80) and high anti-CCP2 levels (OR 1.49, 95% CI 1.25–1.78) were identified as independent risk factors for lung disease in the RA population.

Conclusion.

High anti-CCP2 levels are associated with lung disease in the RA population.
La búsqueda de información con fines académicos entre el alumnado universitario
Authors: Comas Rubén , Sureda Jaume , Pastor Miquel , Morey Mercé
Published: March 2011

En este trabajo se presentan los resultados de un estudio sobre la autovaloración de los conocimientos y habilidades del alumnado pregraduado de la Universidad de las Islas Baleares (UIB) para la búsqueda de información con fines académicos. También se describen diversos aspectos sobre la utilización de algunos servicios bibliotecarios así como de Internet. El estudio se basó en la aplicación de un cuestionario a un total de 1.025 universitarios seleccionados aleatoriamente. De los resultados alcanzados se desprende que el alumnado universitario se considera, por norma general, competente en el manejo de Internet para documentarse con fines académicos, pero no en el uso de las bibliotecas. Lógicamente, la frecuencia de uso de Internet también es muy superior a la de los otros recursos de búsqueda de información académica. Cabe plantear, en este sentido, la necesidad de mejorar las competencias y estrategias de documentación del alumnado basadas en el uso de las bibliotecas, recurso que no excluye el empleo de Internet, pero que a buen seguro puede mejorar la búsqueda documental en aspectos como el rigor, la fiabilidad y la potencialidad de cubrir mucho mejor las necesidades informacionales del alumnado.
Nueva etapa de la base de datos Bibliografía Histórica sobre la Ciencia y la Técnica en España
Authors: López Terrada M.ª Luz , Osca-Lluch Julia , Marti Francisco , Morales Jesús
Published: March 2011

Se describen las características y cambios experimentados en la base de datos Bibliografía Histórica sobre la Ciencia y la Técnica en España, producida por el Instituto de Historia de la Medicina y de la Ciencia López Piñero (UV-CSIC), que tiene como objetivo principal recoger la totalidad de la producción científica de historia de la ciencia y de la técnica publicada en España, así como la realizada por autores españoles, publicada tanto a nivel nacional como internacional.
Definition of buried archaeological remains with a new 3D visualization technique of a ground‐penetrating radar data set in Temple Augustus in Ankara, Turkey
Authors: Kadioglu Selma
Published: March 2011

The aim of this paper is to image particularly buried archaeological remains with a new technique for 3D display in the Temple of Augustus (Monumentum Ancyranum) relating to the Roman time, around and in Agora in the Ulus district of Ankara, Turkey. 2D ground‐penetrating radar (GPR) data were acquired on constant spaced parallel profiles in the study area. After data processing, a 3D data volume was built using a parallel 2D data set. The full data block was divided into sub‐data blocks in time. A weak amplitude range was made invisible with zero opaque by applying zero opacity to these values in the visualization. The arranged visible maximum amplitude range was enlarged or the amplitude scale was weighted with a constant coefficient, which was greater than one and smaller than two and had a decimal number, according to the time range. In this way, a transparent 3D image was obtained for determining buried remains according to the depth range. Interactive visualization was carried out by constructing sub‐blocks of the transparent 3D volume.

The interactive transparent 3D visualization was provided to identify the archaeological remains on native locations with depth in a 3D volume. Very complex and deep wall structures were visualized with any depth range inside (cella) of the Temple of Augustus and a few very narrow cubic anomalies exceeding 4 m deep were determined at the East side of the temple. An excavation could not be carried out in the cella because of the sensitivity problem of the cella walls. However, excavations in front of the East wall of the temple encouraged the new 3D image results. In addition, a lot of iron clamps connecting wall marble stones were determined on a profile gathered on the East wall.
« Verser notre sang, non celui des autres »
Authors: Castelli Elizabeth A.
Published: March 2011

Dans les jours qui ont précédé l’invasion américaine de l’Irak en 2003, quatre militants catholiques ont réalisé un acte de contestation spectaculaire dans un centre de recrutement militaire situé dans un centre commercial de l’État de New York. Par le geste symbolique de verser leur propre sang, ils ont tenté de rendre visible le sang de la guerre. La scène du drame s’est rapidement déplacée du centre de recrutement au tribunal lorsque les militants ont été accusés d’avoir ainsi perpétré une série de crimes contre l’État. Cet article analyse le débat qui s’est développé autour du statut du sang – élément sacramentel ou criminel – afin de comprendre les enjeux de la contestation et des poursuites judiciaires auxquelles elle a donné lieu.
Pourquoi saigner ?
Authors: Sanabria Emilia
Published: March 2011

Plutôt que de s’interroger sur les significations du sang, cet article examine donc la façon dont les gens connaissent, administrent et régulent l’état de leur sang. À Salvador de Bahia, au Brésil – dans un contexte où sont débattues la suppression de la menstruation et les pratiques de don du sang –, quelles logiques guident le choix de saigner ou non ? C’est le sang qui, en premier lieu, est affecté par une rupture dans l’équilibre corporel. Rénover le sang en expurgeant son excès permet de le purifier et de moduler la qualité de cette substance en permanente transformation. C’est ainsi que les idées développées à Bahia sur le sang associent avec ingéniosité les antiques notions humorales et les techniques biomédicales contemporaines.
La « vie sociale » du sang (Penang, Malaisie)
Authors: Carsten Janet
Published: March 2011

Le sang est, dans de nombreuses cultures, un symbole central de la parenté, de l’ethnicité et de la religion ; il est aussi un objet d’investigation scientifique ou médicale, tout comme une source précieuse de traitement médical. Si la distinction entre des ordres de savoirs, qui mettrait le savoir scientifique à l’écart des savoirs sur la parenté, est une idée qui semble paradigmatique de la modernité, qu’est-ce qui contribue à créer de telles frontières ? Dans quelle mesure ces séparations sont-elles strictement maintenues ? Existe-t-il des domaines dans lesquels on peut détecter une interpénétration entre un type de savoir et un autre ? Prenant appui sur une étude ethnographique de dispositifs biomédicaux en Malaisie, et sur des comparaisons plus générales, cet article explore les voies par lesquelles le sang circule entre des aires de savoir et de pratique que nous concevons comme « scientifique » ou « biomédicale », et des aires qui sont, en apparence, plus ouvertement modelées par la culture – telles la parenté, l’ethnicité et la religion.
Du don à l’industrie
Authors: Chauveau Sophie
Published: March 2011

L’histoire de la transfusion sanguine en France des années 1940 aux années 2000 est exemplaire de la transformation du statut du sang sous l’effet des découvertes scientifiques, des innovations thérapeutiques et des attentes des médecins et des malades. Parce que le sang ne peut être vendu, il incombe à l’État d’organiser la transfusion de manière à préserver le don du sang bénévole, anonyme et gratuit. Le changement technique, l’essor de nouvelles thérapeutiques, le risque sanitaire ont imposé des réformes, depuis les années 1990, qui positionnent aujourd’hui la transfusion entre l’État et le marché.
La réserve de Neot Kedumim en Israël : l’écriture d’un paysage
Authors: Friedman Sylvie
Published: March 2011

La réserve de paysages bibliques de Neot Kedumim articule les plantes et les paysages de façon à les relier aux valeurs culturelles et sociales juives. Le projet initial, calqué sur les idéaux sionistes et le contexte national de création de l’État d’Israël, a développé ces dernières années, à l’attention d’un public diasporique en manque d’investissement identitaire, une vocation à la fois touristique et mémorielle. Celle-ci conjugue des activités de plantation et l’expérimentation d’une scène naturelle qui serait à la fois un produit de l’histoire et des textes traditionnels.
La Nouvelle Droite et les Indo-Européens
Authors: François Stéphane
Published: March 2011

La question indo-européenne passionne l’extrême droite occidentale depuis l’après-guerre, et passionne en particulier la Nouvelle Droite. Les différentes tendances de celle-ci n’entendaient pas l’abandonner malgré le discrédit et la suspicion qu’ont connus ces études à la suite de l’avènement de l’Allemagne nazie et de ses études raciologiques. Dès lors, il importait surtout pour ces extrêmes droites d’élaborer de nouveaux discours reprenant leurs vieilles thèses, telles celles élaborées par Hans F. K. Günther. Nous verrons comment celles-ci ont renouvelé leurs références afin d’échapper aux accusations de racisme et de nordicisme.
B Cells as a Therapeutic Target for IFN-β in Relapsing–Remitting Multiple Sclerosis
Authors: Ramgolam Vinod S. , Sha Yonggang , Marcus Karen L. , Choudhary Neelima , Troiani Luigi , Chopra Manisha , Markovic-Plese Silva
Published: March 2011

IFN-β-1b is a first-line immunomodulatory therapy for relapsing–remitting multiple sclerosis (RR MS). However, its effects on B cells have not been characterized. In vitro studies of B cells derived from RR MS patients revealed that IFN-β-1b decreases B cells’ stimulatory capacity, as detected by inhibition of the Ag-specific T cell proliferative response upon Ag presentation by IFN-β-1b–treated B cells. Our study has identified that IFN-β-1b inhibited B cells’ stimulatory capacity in RR MS patients and healthy controls through the suppression of CD40 and CD80 expression, whereas the MHC class I and II expression was not changed. IFN-β-1b in vitro treatment inhibited B cell secretion of IL-1β and IL-23 and induced IL-12 and IL-27. Supernatants transferred from IFN-β-1b–treated B cells inhibited Th17 cell differentiation, as they suppressed gene expression of the retinoic acid-related orphan nuclear hormone receptor C and IL-17A and secretion of IL-17A. In addition, IFN-β-1b induced B cells’ IL-10 secretion, which may mediate their regulatory effect. Studies of B cells derived from RR MS patients treated with recombinant s.c. injected IFN-β-1b revealed that they induced a significantly lower proliferative response in allogenic MLR than the B cells from untreated patients. Further confirming the IFN-β-1b in vitro-induced changes in B cell cytokine secretion, B cells derived from the IFN-β-1b–treated patients secreted significantly lower levels of IL-1β and IL-23 and higher levels of IL-12 and IL-27 in comparison with the B cells derived from untreated patients. We conclude that IFN-β-1b exerts its therapeutic effects in part by targeting B cells’ functions that contribute to the autoimmune pathogenesis of RR MS.
Angiopoietin 2 Stimulates TIE2-Expressing Monocytes To Suppress T Cell Activation and To Promote Regulatory T Cell Expansion
Authors: Coffelt Seth B. , Chen Yung-Yi , Muthana Munitta , Welford Abigail F. , Tal Andrea O. , Scholz Alexander , Plate Karl H. , Reiss Yvonne , Murdoch Craig , De Palma Michele , Lewis Claire E.
Published: March 2011

Angiopoietin 2 (ANGPT2) is a proangiogenic cytokine whose expression is often upregulated by endothelial cells in tumors. Expression of its receptor, TIE2, defines a highly proangiogenic subpopulation of myeloid cells in circulation and tumors called TIE2-expressing monocytes/macrophages (TEMs). Genetic depletion of TEMs markedly reduces tumor angiogenesis in various tumor models, emphasizing their essential role in driving tumor progression. Previously, we demonstrated that ANGPT2 augments the expression of various proangiogenic genes, the potent immunosuppressive cytokine, IL-10, and a chemokine for regulatory T cells (Tregs), CCL17 by TEMs in vitro. We now show that TEMs also express higher levels of IL-10 than TIE2− macrophages in tumors and that ANGPT2-stimulated release of IL-10 by TEMs suppresses T cell proliferation, increases the ratio of CD4+ T cells to CD8+ T cells, and promotes the expansion of CD4+CD25highFOXP3+ Tregs. Furthermore, syngeneic murine tumors expressing high levels of ANGPT2 contained not only high numbers of TEMs but also increased numbers of Tregs, whereas genetic depletion of tumor TEMs resulted in a marked reduction in the frequency of Tregs in tumors. Taken together, our data suggest that ANGPT2-stimulated TEMs represent a novel, potent immunosuppressive force in tumors.
Common Lymphatic Endothelial and Vascular Endothelial Receptor-1 Mediates the Transmigration of Regulatory T Cells across Human Hepatic Sinusoidal Endothelium
Authors: Shetty Shishir , Weston Christopher J. , Oo Ye H. , Westerlund Nina , Stamataki Zania , Youster Janine , Hubscher Stefan G. , Salmi Marko , Jalkanen Sirpa , Lalor Patricia F. , Adams David H.
Published: March 2011

The common lymphatic endothelial and vascular endothelial receptor (CLEVER-1; also known as FEEL-1 and stabilin-1) is a recycling and intracellular trafficking receptor with multifunctional properties. In this study, we demonstrate increased endothelial expression of CLEVER-1/stabilin-1 at sites of leukocyte recruitment to the inflamed human liver including sinusoids, septal vessels, and lymphoid follicles in inflammatory liver disease and tumor-associated vessels in hepatocellular carcinoma. We used primary cultures of human hepatic sinusoidal endothelial cells (HSEC) to demonstrate that CLEVER-1/stabilin-1 expression is enhanced by hepatocyte growth factor but not by classical proinflammatory cytokines. We then showed that CLEVER-1/stabilin-1 supports T cell transendothelial migration across HSEC under conditions of flow with strong preferential activity for CD4 FoxP3+ regulatory T cells (Tregs). CLEVER-1/stabilin-1 inhibition reduced Treg transendothelial migration by 40% and when combined with blockade of ICAM-1 and vascular adhesion protein-1 (VAP-1) reduced it by >80%. Confocal microscopy demonstrated that 60% of transmigrating Tregs underwent transcellular migration through HSEC via ICAM-1– and VAP-1–rich transcellular pores in close association with CLEVER-1/stabilin-1. Thus, CLEVER-1/stabilin-1 and VAP-1 may provide an organ-specific signal for Treg recruitment to the inflamed liver and to hepatocellular carcinoma.
Identification of a New Phenotype of Tolerogenic Human Dendritic Cells Induced by Fungal Proteases from Aspergillus oryzae
Authors: Zimmer Aline , Luce Sonia , Gaignier Fanny , Nony Emmanuel , Naveau Marie , Biola-Vidamment Armelle , Pallardy Marc , Van Overtvelt Laurence , Mascarell Laurent , Moingeon Philippe
Published: March 2011

We characterized a new pathway to induce tolerogenic dendritic cells (DCs) following treatment of human monocyte-derived DCs with proteases from the fungus Aspergillus oryzae (ASP). ASP-treated DCs (ASP-DCs) exhibit a CD80−CD83−CD86−Ig-like transcript (ILT)2−ILT3−ILT4+ phenotype, do not secrete cytokines or chemokines, and express tolerogenic markers such as glucocorticoid-induced leucine zipper, NO synthetase-2, retinaldehyde dehydrogenase-1 or retinaldehyde dehydrogenase-2. When cocultured with naive CD4+ T cells, ASP-DCs induce an anergic state that can be reversed by IL-2. Generated T cells mediate a suppressive activity in third-party experiments that is not mediated by soluble factors. A comparison between dexamethasone-treated DCs used as a reference for regulatory T cell-inducing DCs and ASP-DCs reveals two distinct phenotypes. In contrast to dexamethasone, ASP treatment induces glucocorticoid-induced leucine zipper independently of glucocorticoid receptor engagement and leads to NF-κB p65 degradation. Abrogation of protease activities in ASP using specific inhibitors reveals that aspartic acid-containing proteases are key inducers of regulatory genes, whereas serine, cysteine, and metalloproteases contribute to NF-κB p65 degradation. Collectively, those features correspond to a previously unreported anergizing phenotype for human DCs. Such regulatory mechanisms may allow fungi to downregulate host immune responses and provide clues for new approaches to treat proinflammatory disorders.
Simian Immunodeficiency Virus Infection in the Brain and Lung Leads to Differential Type I IFN Signaling during Acute Infection
Authors: Alammar Luna , Gama Lucio , Clements Janice E.
Published: March 2011

Using an accelerated and consistent SIV pigtailed macaque model of HIV-associated neurologic disorders, we have demonstrated that virus enters the brain during acute infection. However, neurologic symptoms do not manifest until late stages of infection, suggesting that immunological mechanisms exist within the CNS that control viral replication and associated inflammation. We have shown that IFN-β, a type I IFN central to viral innate immunity, is a major cytokine present in the brain during acute infection and is responsible for limiting virus infection and inflammatory cytokine expression. However, the induction and role of IFN-α in the CNS during acute SIV infection has never been examined in this model. In the classical model of IFN signaling, IFN-β signals through the IFN-α/β receptor, leading to expression of IFN-α. Surprisingly, although IFN-β is upregulated during acute SIV infection, we found that IFN-α is downregulated. We demonstrate that this downregulation is coupled with a suppression of signaling molecules downstream of the IFN receptor, namely tyrosine kinase 2, STAT1, and IFN regulatory factor 7, as indicated by either lack of protein phosphorylation, lack of nuclear accumulation, or transcriptional and/or translational repression. In contrast to brain, IFN-α is upregulated in lung and accompanied by activation of tyrosine kinase 2 and STAT1. These data provide a novel observation that during acute SIV infection in the brain, there is differential signaling through the IFN-α/β receptor that fails to activate expression of IFN-α in the brain.
Actions and Invariants of Residually Finite Groups: Asymptotic Methods
Authors: Glauberman George , Gaboriau Damien , Grunewald Fritz
Published: March 2011

The workshop brought together experts in finite group theory, _L_2-cohomology, measured group theory, the theory of lattices in Lie groups, probability and topology. The common object of interest was residually finite groups, that each field investigates from a different angle.
Nonlinear Waves and Dispersive Equations
Authors: Kenig Carlos E. , Koch Herbert , Tataru Daniel
Published: March 2011

The aim of the workshop was to discuss current developments in nonlinear waves and dispersive equations from a PDE based view. The talks centered around rough initial data, long time and global existence, perturbations of special solutions, and applications.
Topologie
Authors: Schick Thomas , Teichner Peter , Wahl Nathalie , Weiss Michael
Published: March 2011

This conference is one of the few occasions where researchers from many different areas in algebraic and geometric topology are able to meet and exchange ideas. Accordingly, the program covered a wide range of new developments in such fields as geometric group theory, rigidity of group actions, knot theory, and stable and unstable homotopy theory. More specifically, we discussed progress on problems such as the Farrell-Jones conjecture, the Levine conjecture in grope cobordism of knots and Rosenberg’s conjecture about homotopy invariance of negative algebraic K-theory, to mention just a few subjects with a name attached. One of the highlights was a series of four talks on the solution of Arf-Kervaire invariant problem by Mike Hill and Doug Ravenel, reporting on their joint work with Mike Hopkins.
Seroprevalence of West Nile Virus in Wild Birds in Far Eastern Russia Using a Focus Reduction Neutralization Test
Authors: Murata Ryo , Hashiguchi Kazuaki , Yoshii Kentaro , Kariwa Hiroaki , Nakajima Kensuke , Ivanov Leonid I. , Leonova Galina N. , Takashima Ikuo
Published: March 2011

West Nile (WN) virus has been spreading geographically to non-endemic areas in various parts of the world. However, little is known about the extent of WN virus infection in Russia. Japanese encephalitis (JE) virus, which is closely related to WN virus, is prevalent throughout East Asia. We evaluated the effectiveness of a focus reduction neutralization test in young chicks inoculated with JE and WN viruses, and conducted a survey of WN infection among wild birds in Far Eastern Russia. Following single virus infection, only neutralizing antibodies specific to the homologous virus were detected in chicks. The neutralization test was then applied to serum samples from 145 wild birds for WN and JE virus. Twenty-one samples were positive for neutralizing antibodies to WN. These results suggest that WN virus is prevalent among wild birds in the Far Eastern region of Russia.
Low Anticoagulant Heparin Disrupts Plasmodium falciparum Rosettes in Fresh Clinical Isolates
Authors: Leitgeb Anna M. , Blomqvist Karin , Cho-Ngwa Fidelis , Samje Moses , Nde Peter , Titanji Vincent , Wahlgren Mats
Published: March 2011

The binding of Plasmodium falciparum parasitized erythrocytes to uninfected erythrocytes (rosetting) is associated with severe malaria. The glycosaminoglycan heparan sulfate is an important receptor for rosetting. The related glycosaminoglycan heparin was previously used in treatment of severe malaria, although abandoned because of the occurrence of severe bleedings. Instead, low anticoagulant heparin (LAH) has been suggested for treatment. LAH has successfully been evaluated in safety studies and found to disrupt rosettes and cytoadherence in vitro and in vivo in animal models, but the effect of LAH on fresh parasite isolates has not been studied. Herein, we report that two different LAHs (DFX232 and Sevuparin) disrupt rosettes in the majority of fresh isolates from Cameroonian children with malaria. The rosette disruption effect was more pronounced in isolates from complicated cases than from mild cases. The data support LAH as adjunct therapy in severe malaria.
Cross-Species Surveillance of Leptospira in Domestic and Peri-Domestic Animals in Mahalla City, Gharbeya Governorate, Egypt
Authors: Felt Stephen A. , Wasfy Momtaz O. , El-Tras Wael F. , Samir Ahmed , Rahaman Bassem Abdel , Boshra Marie , Parker Tina M. , Hatem Mahmoud Essam , El-Bassiouny Ahmed Ahmed , Murray Clinton K. , Pimentel Guillermo
Published: March 2011

A survey of 179 animals (black rats, dogs, sheep, buffaloes, cattle, donkeys, weasels, and cats) for Leptospira infection was conducted in Mahalla City (Lower Egypt). Blood, urine, and kidney were collected and tested by culture, microscopic agglutination test (MAT), and/or polymerase chain reaction (PCR). Among rats, 26% were positive by PCR, including 7% that were also positive by culture for L. interrogans serovars Grippotyphosa, Pyrogenes, and Icterohaemorrhagiae. L. borpetersenii serovar Polonica was isolated for the first time in Egypt in three rats. MAT titers ≥ 1:800 were observed in 11% of rats and 12% of dogs. L. interrogans serovar Grippotyphosa was detected in one cat. Sheep and donkeys were negative for leptospirosis by all methods. Buffaloes and cattle were seropositive in 20% and 44% of animals, respectively. Data indicate that several pathogenic serovars are circulating in the animals, which may pose exposure risks and account for high rates of acute febrile illness.
Urogenital Schistosomiasis in Women of Reproductive Age in Tanzania's Lake Victoria Region
Authors: Downs Jennifer A. , Mguta Charles , Kaatano Godfrey M. , Mitchell Katrina B. , Bang Heejung , Simplice Harusha , Kalluvya Samuel E. , Changalucha John M. , Johnson Warren D. , Fitzgerald Daniel W.
Published: March 2011

We conducted a community-based study of 457 women aged 18–50 years living in eight rural villages in northwest Tanzania. The prevalence of female urogenital schistosomiasis (FUS) was 5% overall but ranged from 0% to 11%. FUS was associated with human immunodeficiency virus (HIV) infection (odds ratio [OR] = 4.0, 95% confidence interval [CI] = 1.2–13.5) and younger age (OR = 5.5 and 95% CI = 1.2–26.3 for ages < 25 years and OR = 8.2 and 95% CI = 1.7–38.4 for ages 25–29 years compared with age > 35 years). Overall HIV prevalence was 5.9% but was 17% among women with FUS. We observed significant geographical clustering of schistosomiasis: northern villages near Lake Victoria had more Schistosoma mansoni infections (P < 0.0001), and southern villages farther from the lake had more S. haematobium (P = 0.002). Our data support the postulate that FUS may be a risk factor for HIV infection and may contribute to the extremely high rates of HIV among young women in sub-Saharan Africa.
New Flagellin Gene for Salmonella enterica serovar Typhi from the East Indonesian Archipelago
Authors: Hatta Mochammad , Sultan Andi R. , Pastoor Rob , Smits Henk L.
Published: March 2011

Phase variation is a property unique of some Salmonella enterica serovar Typhi strains from Indonesia. Salmonella Typhi isolates from Indonesia have been described that in addition to the phase 1 Hd flagellin gene contain a second flagellin gene named z66. S. Typhi isolates from Indonesia with a mutant Hd gene named Hj have also been described. Here, we have identified another flagellin gene of S. Typhi, named Ind, showing a closest homology with the flagellin gene of Serratia marcescens. The Ind gene was detected in 21.8% of the S. Typhi isolates from the East Indonesian archipelago, all of which contained the Hd gene. The Hj gene was not detected. The z66 gene was present in 15.4% of the isolates. The presence of these “foreign” flagellin genes could be associated with an increased risk for developing severe disease.
Diode laser-based cavity ring-down instrument for NO3, N2O5, NO, NO2 and O3 from aircraft
Authors: Wagner N. L. , Dubé W. P. , Washenfelder R. A. , Young C. J. , Pollack I. B. , Ryerson T. B. , Brown S. S.
Published: March 2011

Abstract. This article presents a diode laser based, cavity ring-down spectrometer for simultaneous in situ measurements of four nitrogen oxide species, NO3, N2O5, NO, NO2, as well as O3, designed for deployment on aircraft. The instrument measures NO3 and NO2 by optical extinction at 662 nm and 405 nm, respectively; N2O5 is measured by thermal conversion to NO3, while NO and O3 are measured by chemical conversion to NO2. The instrument has several advantages over previous instruments developed by our group for measurement of NO2, NO3 and N2O5 alone, based on a pulsed Nd:YAG and dye laser. First, the use of continuous wave diode lasers reduces the requirements for power and weight and eliminates hazardous materials. Second, detection of NO2 at 405 nm is more sensitive than our previously reported 532 nm instrument, and does not have a measurable interference from O3. Third, the instrument includes chemical conversion of NO and O3 to NO2 to provide measurements of total NOx (= NO + NO2) and Ox (= NO2 + O3) on two separate channels; mixing ratios of NO and O3 are determined by subtraction of NO2. Finally, all five species are calibrated against a single standard based on 254 nm O3 absorption to provide high accuracy. Disadvantages include an increased sensitivity to water vapor on the 662 nm NO3 and N2O5 channels and a modest reduction in sensitivity for these species compared to the pulsed laser instrument. The measurement precision for both NO3 and N2O5 is below 1 pptv (2σ, 1 s) and for NO, NO2 and O3 is 170, 46, and 56 pptv (2σ, 1 s) respectively. The NO and NO2 measurements are less precise than research-grade chemiluminescence instruments. However, the combination of these five species in a single instrument, calibrated to a single analytical standard, provides a complete and accurate picture of nighttime nitrogen oxide chemistry. The instrument performance is demonstrated using data acquired during a recent field campaign in California.
On the biogeochemical signature of the Lena River from its headwaters to the Arctic Ocean
Authors: Semiletov I. P. , Pipko I. I. , Shakhova N. E. , Dudarev O. V. , Pugach S. P. , Charkin A. N. , McRoy C. P. , Kosmach D. , Gustafsson O.
Published: March 2011

Abstract. The Lena River integrates biogeochemical signals from its vast drainage basin and its signal reaches far out over the Arctic Ocean. Transformation of riverine organic carbon into mineral carbon, and mineral carbon into the organic form in the Lena River watershed, can be considered a quasi-equilibrated processes. Increasing the Lena discharge causes opposite effects on total organic (TOC) and inorganic (TCO2) carbon: TOC concentration increases, while TCO2 concentration decreases. Significant inter-annual variability in mean values of TCO2, TOC, and their sum (TC) has been found. This variability is determined by changes in land hydrology which cause differences in the Lena River discharge, because a negative correlation may be found between TC in September and mean discharge in August (a time shift of about one month is required for water to travel from Yakutsk to the Laptev Sea). Total carbon entering the sea with the Lena discharge is estimated to be almost 10 Tg C y−1. The annual Lena River discharge of particulate organic carbon (POC) may be equal to 0.38 Tg (moderate to high estimate). If we instead accept Lisytsin's (1994) statement concerning the precipitation of 85–95% of total particulate matter (PM) (and POC) on the marginal "filter", then only about 0.03–0.04 Tg of POC reaches the Laptev Sea from the Lena River. The Lena's POC export would then be two orders of magnitude less than the annual input of eroded terrestrial carbon onto the shelf of the Laptev and East Siberian seas, which is about 4 Tg. The Lena River is characterized by relatively high concentrations of primary greenhouse gases: CO2 and dissolved CH4. During all seasons the river is supersaturated in CO2 compared to the atmosphere: up to 1.5–2 fold in summer, and 4–5 fold in winter. This results in a narrow zone of significant CO2 supersaturation in the adjacent coastal sea. Spots of dissolved CH4 in the Lena delta channels may reach 100 nM, but the CH4 concentration decreases to 5–20 nM towards the sea, which suggests only a minor role of riverborne export of CH4 for the East Siberian Arctic Shelf (ESAS) CH4 budget in coastal waters. Instead, the seabed appears to be the source that provides most of the CH4 to the Arctic Ocean.
Plant communities as drivers of soil respiration: pathways, mechanisms, and significance for global change
Authors: Metcalfe D. B. , Fisher R. A. , Wardle D. A.
Published: March 2011

Abstract. Understanding the impacts of plant community characteristics on soil carbon dioxide efflux (R) is a key prerequisite for accurate prediction of the future carbon balance of terrestrial ecosystems under climate change. In this review, we synthesize relevant information from a wide spectrum of sources to evaluate the current state of knowledge about plant community effects on R, examine how this information is incorporated into global climate models, and highlight priorities for future research. Plant species consistently exhibit cohesive suites of traits, linked to contrasting life history strategies, which exert a variety of impacts on R. As such, we propose that plant community shifts towards dominance by fast growing plants with nutrient rich litter could provide a major, though often neglected, positive feedback to climate change. Within vegetation types, belowground carbon flux will mainly be controlled by photosynthesis, while amongst vegetation types this flux will be more dependent upon the specific characteristics of the plant life form. We also make the case that community composition, rather than diversity, is usually the dominant control on ecosystem processes in natural systems. Individual species impacts on R may be largest where the species accounts for most of the biomass in the ecosystem, has very distinct traits to the rest of the community, or modulates the occurrence of major natural disturbances. We show that climate-vegetation models incorporate a number of pathways whereby plants can affect R, but that simplifications regarding allocation schemes and drivers of litter decomposition may limit model accuracy. This situation could, however, be relatively easily improved with targeted experimental and field studies. Finally, we identify key gaps in knowledge and recommend them as priorities for future work. These include the patterns of photosynthate partitioning amongst belowground components, ecosystem level effects of individual plant traits, and the importance of trophic interactions and species invasions or extinctions for ecosystem processes. A final, overarching challenge is how to link these observations and drivers across spatio-temporal scales to predict regional or global changes in R over long time periods. A more unified approach to understanding R, which integrates information about plant traits and community dynamics, will be essential for better understanding, simulating and predicting feedbacks to R across terrestrial ecosystems and the earth-climate system.