Immune Complexes in Juvenile Idiopathic Arthritis

Abstract for invited review in Molecular Mechanisms of Immune Complex Pathophysiology thematic issue to be published in Frontiers in Immunology. Immune Complexes(IC)in Juvenile Idiopathic Arthritis (JIA) Terry L. Moore, MD, FAAP, FACR, MACR Professor of Internal Medicine,Pediatrics, and Molecular Biology and Immunology Director of Adult and Pediatric Rheumatology Saint Louis University School of Medicine Saint Louis, Missouri 631`04,USA Juvenile idiopathic arthritis (JIA) reflects a group of clinically heterogeneous, autoimmune disorders in children characterized by chronic arthritis and hallmarked by elevated levels of circulating immune complexes (CICs) and associated complement activation by-products in their sera. ICs have been detected in patients’ sera with JIA utilizing a variety of methods, including the anti-human IgM affinity column,C1q solid phase assay, polyethylene glycol precipitation, Staphylococcal Protein A separation method, anti-C1q/C3 affinity columns, and FcγRIII affinity method. As many as 75% of JIA patients have had IC detected in their sera. The CIC proteome in JIA patients has been examined to elucidate disease-associated proteins that are expressed in active disease. Evaluation of these IC s have shown the presence of multiple peptide fragments by SDS-PAGE and 2-DE. Subsequently, all isotypes of rheumatoid factor (RF), isotypes of anti-cyclic citrullinated (CCP) peptide antibodies, IgG, C1q, C4, C3, and the membrane attack complex (MAC) were detected in these IC. Complement activation and levels of IC correlate with disease activity in JIA, indicating their role in the pathophysiology of the disease. This review will summarize the existing literature and discuss the role of possible protein modification that participates in the generation of immune response. We will address the possible role of these events in the development of ectopic germinal centers that become the secondary site of plasma cell development in JIA. We will further address possible therapeutic modalities that could be instituted as a result of the information gathered by the presence of ICs in JIA

The Effect of Binaural Auditory Beats on the Anxiety and Psychological Hardiness Levels of Graduate Students

Three graduate students from a Midwestern urban university were selected from a pool of volunteers based on elevated levels of anxiety. The students were initially tested using the Self-Evaluation Questionnaire and Hardiness Scale. Students were provided with audio tapes using binaural beats. Each Self-Evaluation Questionnaire score was tracked for the purpose of determining the affect of the audio tapes on levels of anxiety and hardiness. All three students showed reduced levels of anxiety after using the tapes, with either a similar or higher level of Hardiness

Using administrative data to monitor racial/ethnic disparities and disproportionality within child welfare agencies: process and preliminary outcomes

Child welfare administrative data are increasingly used to identify racial/ethnic disproportionality and disparities at various levels of aggregation. However, child welfare agencies typically face challenges in harnessing administrative data to examine racial/ethnic disproportionality and disparities at meaningful levels of analysis due to limited resources and/or tools for reporting. This article describes the process through which a multi-state workgroup designed and developed management reports to monitor racial/ethnic disparities and disproportionality using a web-based child welfare administrative data reporting system. The article provides an overview of the process, outcome, and challenges of the group’s work with the goal of offering a starting point for discussion to others who may be seeking to monitor racial/ethnic disparities and disproportionality, regardless of their reporting system

Evidence of fibrinogen as a target of citrullination in IgM rheumatoid factor-positive polyarticular juvenile idiopathic arthritis

<p>Abstract</p> <p>Background</p> <p>Several studies have noted the significance of measuring anti-cyclic citrullinated peptide (CCP) antibodies in juvenile idiopathic arthritis (JIA) as an important indicator for destructive disease, as is the case in rheumatoid arthritis (RA). While the role of anti-CCP antibodies in RA and JIA has become better understood, the identity of the target proteins of this modification has remained elusive. In this study, we evaluated serum from patients with various subtypes of JIA to investigate the presence of anti-deiminated (citrullinated) fibrinogen and anti-citrullinated α-enolase antibodies, and their association with RF and anti-CCP antibody isotypes.</p> <p>Methods</p> <p>Sera were obtained from 96 JIA patients, 19 systemic lupus erythematosus (SLE) patients, and 10 healthy children. All sera were measured for antibodies against citrullinated and native fibrinogen and α-enolase by an enzyme linked immunosorbent assay (ELISA). In addition, all sera were assayed for anti-CCP antibody isotypes and rheumatoid factor (RF) isotypes by ELISA. The relationship between anti-citrullinated fibrinogen and anti-α-enolase antibodies and disease activity and joint damage were also investigated. All results were correlated with clinical and laboratory parameters using Spearman's rho correlation coefficient. Multiple logistic regression analysis was utilized to identify which variables were associated with joint erosions and diagnosis of JIA.</p> <p>Results</p> <p>Thirty-one JIA patients (32%) demonstrated reactivity to citrullinated fibrinogen and 9 (9%) to citrullinated α-enolase. Reactivity to citrullinated fibrinogen and α-enolase was predominantly found in IgM RF-positive polyarthritis patients. Fourteen JIA patients reacted with native α-enolase and a higher percentage of SLE patients reacted with citrullinated α-enolase when compared to JIA patients. Anti-citrullinated fibrinogen antibodies correlated with the presence of IgG anti-CCP antibodies and IgA and IgM RF. The presence of anti-citrullinated α-enolase antibodies correlated with IgA anti-CCP antibodies. IgG anti-CCP antibodies were significantly associated with joint damage and anti-citrullinated fibrinogen antibodies were strongly associated with JIA when compared to control groups. Anti-citrullinated fibrinogen antibodies demonstrated high sensitivity (81%) for IgM RF-positive polyarticular JIA. IgG anti-CCP antibodies had the highest specificity (95%) for JIA, with anti-citrullinated fibrinogen antibodies, IgA anti-CCP antibodies and IgA RF all following at 84%.</p> <p>Conclusions</p> <p>JIA patient sera exhibited strong reactivity to anti-citrullinated fibrinogen antibodies and demonstrated high sensitivity and specificity for JIA, primarily in IgM RF-positive polyarthritis patients. Fibrinogen is one of several protein targets for citrullination in JIA.</p

CCN Data Interpretation Under Dynamic Operation Conditions

We have developed a new numerical model for the non-steadystate operation of the Droplet Measurement Technologies (DMT) Cloud Condensation Nuclei (CCN) counter. The model simulates the Scanning Flow CCN Analysis (SFCA) instrument mode, where a wide supersaturation range is continuously scanned by cycling the flowrate over 20–120 s. Model accuracy is verified using a broad set of data which include ammonium sulfate calibration data (under conditions of low CCN concentration) and airborne measurements where either the instrument pressure was not controlled or where exceptionally high CCN loadings were observed. It is shown here for the first time that small pressure and flow fluctuations can have a disproportionately large effect on the instrument supersaturation due to localized compressive/expansive heating and cooling. The model shows that, for fast scan times, these effects can explain the observed shape of the SFCA supersaturation-flow calibration curve and transients in the outlet droplet sizes. The extent of supersaturation depletion from the presence of CCN during SFCA operation is also examined; we found that depletion effects can be neglected below 4000 cm−3 for CCN number

GNSS-based Location Determination System Architecture for railway performance assessment in presence of local effects

GNSS plays a strategic role on the introduction of the Virtual Balise functionality and the train integrity. Thanks to GNSS, it could be possible to realize cost effective solutions to increase the safety in the regional lines, where the traffic density is lower. The train position estimation is implemented taking into account that the train is constrained to lie on the track (i.e. track constraint). In this way, we can express the position in terms of the curvilinear abscissa (progressive mileage) of the track corresponding to the train position. However, the impact of local effects such as multipath, foliage attenuation and shadowing in the railway environment plays a crucial role due to the presence of infrastructures like platform roofs, side walls, tunnel entrances, buildings and so on close to the trackside. In the paper, we analyse the impact of those threats on the train GNSS-based position estimation performance. At this aim, several scenarios have been generated by using both real data acquired on a railway test-bed in Sardinia, and synthetic data generated in the lab through ad hoc multipath and foliage models. A sensitivity analysis has been conducted, varying main scenarios parameters (e.g. height of obstacles, presence of trees and shadowing). The result of the performed analysis, in terms of availability, accuracy and integrity, are here presented. mitigations implemented by the ERTMS at system level are not considered since the attention is focused on GNSS only

Twisted brane charges for non-simply connected groups

The charges of the twisted branes for strings on the group manifold SU(n)/Z_d are determined. To this end we derive explicit (and remarkably simple) formulae for the relevant NIM-rep coefficients. The charge groups of the twisted and untwisted branes are compared and found to agree for the cases we consider.Comment: 30 page

Love as a Regulative Ideal in Surrogate Decision Making

This discussion aims to give a normative theoretical basis for a “best judgment” model of surrogate decision making rooted in a regulative ideal of love. Currently, there are two basic models of surrogate decision making for incompetent patients: the “substituted judgment” model and the “best interests” model. The former draws on the value of autonomy and responds with respect; the latter draws on the value of welfare and responds with beneficence. It can be difficult to determine which of these two models is more appropriate for a given patient, and both approaches may seem inadequate for a surrogate who loves the patient. The proposed “best judgment” model effectively draws on the values incorporated in each of the traditional standards, but does so because these values are important to someone who loves a patient, since love responds to the patient as the specific person she is

Ozone loss derived from balloon-borne tracer measurements and the SLIMCAT CTM

Balloon-borne measurements of CFC-11 (on flights of the DIRAC in situ gas chromatograph and the DESCARTES grab sampler), ClO and O3 were made during the 1999/2000 winter as part of the SOLVE-THESEO 2000 campaign. Here we present the CFC-11 data from nine flights and compare them first with data from other instruments which flew during the campaign and then with the vertical distributions calculated by the SLIMCAT 3-D CTM. We calculate ozone loss inside the Arctic vortex between late January and early March using the relation between CFC-11 and O3 measured on the flights, the peak ozone loss (1200 ppbv) occurs in the 440–470 K region in early March in reasonable agreement with other published empirical estimates. There is also a good agreement between ozone losses derived from three independent balloon tracer data sets used here. The magnitude and vertical distribution of the loss derived from the measurements is in good agreement with the loss calculated from SLIMCAT over Kiruna for the same days