bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing Network-Level Decision Making through the use of a Structural Capacity Index
Authors: Bryce James , Flintsch Gerardo , Katicha Samer , Diefenderfer Brian
Published: November 2013

The objective of this study was to show potential applications of a network-level structural index developed for evaluation of flexible pavements. First, several potential applications for implementation of network-level structural measures were identified, and then data from the state of Virginia were used to modify the proposed applications for the index and show examples of them. Several applications were validated with data from network-level deflection testing with the falling weight deflectometer on Interstate highways in Virginia and data from the Virginia Department of Transportation Pavement Management System. The results of the research indicate that including the structural index in the network-level decision process can facilitate a greater understanding of the behavior of the performance of a pavement. Furthermore, the index that was proposed for network-level evaluation of flexible pavements in Virginia was used to develop enhanced deterioration models for particular pavement treatments and to demonstrate the dependence of pavement performance on its structural capacity. It was shown that the functional characteristics of a pavement alone were not adequate to describe the structural condition of the pavement. Therefore, the structural condition, for example, as based on the results of deflection testing, should be considered when network-level pavement management decisions are made.
Probabilistic Characterization of Uncertain Inputs in the Life-Cycle Cost Analysis of Pavements
Authors: Swei Omar , Gregory Jeremy , Kirchain Randolph
Published: November 2013

Life-cycle cost analysis (LCCA) is an important tool for evaluating the merits of alternative investments. Inevitably, inputs for an LCCA are subject to a high level of uncertainty in both the short and long term. However, the way LCCA is currently implemented in the field treats LCCA inputs as static, deterministic values. Conducting an analysis in this way, though computationally simpler, hides the underlying uncertainty of the inputs by only considering a few possible permutations. The results of such an analysis could potentially lead a decision maker to the incorrect pavement selection. One methodology that has gained traction in the past decade is describing uncertain parameters probabilistically and allowing the analysis to consider a range of possible outcomes. Although this methodology is recommended by FHWA, practitioners still generally conduct deterministic LCCAs. One of the major reasons is that further work must be conducted to characterize uncertainty statistically for input parameters. This research attempted to build on previous work by probabilistically characterizing several input parameters for which empirical data were and were not readily available. This paper characterizes uncertainty and variability in the LCCA of pavements and then applies the methodology presented to two case studies to understand the implications of a probabilistic LCCA for the pavement selection process.
Pavement Condition States before and after Treatment
Authors: Dean Christopher M. , Baladi Gilbert Y.
Published: November 2013

When a pavement section is subjected to preservation or rehabilitation treatment, its surface condition is transformed from one set of condition states—those before treatment—to another set—those after treatment. This transformation is a function of the pavement condition before treatment, the type and timing of treatment, the project boundaries, and the quality of construction. For most pavement sections, the surface condition before and after treatment varies substantially along the section and over time. This study sponsored by FHWA analyzed the distribution of pavement surface condition and distress before and after treatment along several flexible pavement projects in the state of Louisiana. The study showed that current practices regarding the selection of pavement treatment type, treatment time, and project boundaries were independent of pavement surface condition and distress before treatment. For all pavement projects that received certain types of treatment in the past, knowledge of the relationships between the before- and after-treatment distributions of the pavement's surface condition and distress was crucial to the establishment of a future cost-effective strategy for pavement treatment. This paper shows that such relationships can be expressed by the probabilities of transforming before-treatment condition states to after-treatment condition states. These probabilities can be housed in one matrix format called the treatment transition matrix (TTM). For each treatment type, the TTM presents a snapshot of the state of the practice.
Innovative Sprinkle Treatment for Thin Durable Asphalt Overlays
Authors: Son Songsu , Al-Qadi Imad L. , Lippert David L. , Zehr Thomas G.
Published: November 2013

This paper presents techniques for improving asphalt overlays through the use of innovative surfacing technologies that employ durable local aggregates spread on a cost-effective wearing surface base mixture. A few states have used the sprinkle treatment to improve the skid resistance of pavement surfaces on top of typical asphalt pavements. Numerous approaches have been introduced to improve the performance of asphalt pavement. These improvements often add cost because they use high-quality aggregates and modified binder. Because sustainable and cost-effective pavements are being emphasized, innovative application of the sprinkle treatment has been considered. A fine-graded dense asphalt wearing surface mixture developed with the Bailey method provides a promising aggregate structure that makes it possible to ensure compactibility with relatively thinner layers of asphalt mixture. The design of the base mixture used less-expensive local aggregates, and its performance was compared in the laboratory with that of two control mixtures to evaluate durability, rut resistance, moisture susceptibility, fracture, and complex modulus. To evaluate the performance of sprinkle treatment pavements under real traffic loading, test pavements of various thicknesses were constructed in northern Illinois during October and November 2010. On-site performance tests that included noise, friction, rut depth, and texture profiles were conducted at 4-month intervals after construction. The study concluded that it is feasible to use a cost-effective alternative wearing surface that performs well.
Evaluation of the Effectiveness of Mississippi's Pavement Warranty Program
Authors: Qi Yan , Wang Feng , Gendy Amin El , Li Yibo
Published: November 2013

More and more state highway agencies have adopted pavement warranty programs in their project contracting to foster contractor innovation, enhance pavement performance, reduce agency costs, and preserve the investment in pavement construction. The Mississippi Department of Transportation (DOT) initiated its pavement warranty program in 2000. This study evaluated the effectiveness of that program on the basis of the international roughness index and data on rutting, cracking, and other typical surface distresses collected and stored in the database of the agency's pavement management system. The distribution of this pavement performance data at different lengths of service was developed for both warranted and nonwarranted projects to reveal the pavement performance characteristics under the two contracting methods. Pair-wise comparison of the distribution of the pavement performance data at different lengths of service was conducted to investigate pavement deterioration patterns over time for both warranted and nonwarranted pavements. Finally, two-sample t-tests were performed to compare the performance of warranted and nonwarranted pavements at the same length of service. The results of the study showed that the deterioration rate of the warranted pavements was slower than that of the nonwarranted pavements and that the performance of the warranted pavements was superior to that of the nonwarranted pavements at the same length of service. On the basis of the statistical analyses, it could be concluded that the pavement warranty program in Mississippi can effectively improve the pavement performance for the state.
Impact of Error in Pavement Condition Data on the Output of Network-Level Pavement Management Systems
Authors: Saliminejad Siamak , Gharaibeh Nasir G.
Published: November 2013

The quality of pavement condition data is important not only in assessing the current condition of the network but also in predicting its future condition and planning future maintenance and rehabilitation (M&R) activities. This paper provides a quantitative assessment of the impact of error magnitude and type (systematic and random) in pavement condition data on the accuracy of pavement management system (PMS) outputs (i.e., forecasted needed budget and M&R activities in a multiyear planning period). The process developed to simulate the propagation of pavement condition errors to PMS output consisted of five components: condition data generation, error perturbation, condition prediction, M&R prioritization, and output generation. This process was applied to the 2011 pavement condition data set of the Bryan District of the Texas Department of Transportation. In 2011, the roadway network of the Bryan District consisted of approximately 3,200 roadbed centerline miles. The study results show that both systematic and random errors can highly distort some PMS output parameters, even in error ranges that may be considered acceptable in practice. These effects tend to persist throughout the planning period. The findings of this study can help highway agencies optimize processes for collecting pavement condition data by focusing on error levels and types that cause the greatest impact on PMS output.
Improved Method for Evaluating the Pavement Structural Number with Falling Weight Deflectometer Deflections
Authors: Kim Moo Yeon , Kim Dae Young , Murphy Michael R.
Published: November 2013

The pavement structural number (SN) is used in various applications worldwide. One application is the structural condition index. The structural condition index was developed for the Texas Department of Transportation (DOT) to support maintenance and rehabilitation decisions at the network level and is calculated as the ratio of two SN values (effective SN/required SN). A direct method of determining the SN from falling weight deflectometer (FWD) testing has been used to evaluate the effective SN. This study sought to increase the accuracy of the structural condition index by improving the method of determining the effective SN from FWD deflection data. A new equation was developed by modifying the equation that was previously used, and new coefficients for four different flexible pavement types were used. The new equation was improved by the addition of new variables for considering the depth to a rigid layer and by the use of a large database consisting of hypothetical pavement structures and responses. This effort not only benefits the Texas DOT by allowing increased accuracy in implementing the structural condition index but also helps other agencies improve their evaluation of the SN by FWD deflection at the network level. In this study, only surface-treated pavement and asphalt concrete pavement were evaluated; portland cement concrete pavement was not addressed.
Disease Control and Safety of Belimumab Plus Standard Therapy Over 7 Years in Patients with Systemic Lupus Erythematosus
Authors: Ginzler Ellen M. , Wallace Daniel J. , Merrill Joan T. , Furie Richard A. , Stohl William , Chatham W. Winn , Weinstein Arthur , McKay James D. , McCune W. Joseph , Zhong Z. John , Freimuth William W. , Petri Michelle A. ,   The LBSL02/99 Study Group
Published: November 2013

Objective.

To evaluate the efficacy/safety of belimumab plus standard therapy in patients (n = 449) with active systemic lupus erythematosus (SLE) treated up to 7 years (n = 177 currently ongoing).

Methods.

Patients (n = 345) who completed a double-blind, placebo-controlled, 52-week study of belimumab 1, 4, or 10 mg/kg and 24-week extension of belimumab (placebo switched to 10 mg/kg; belimumab same dose or switched to 10 mg/kg) could receive belimumab 10 mg/kg in an open-label continuation study (n = 296). Disease activity was analyzed in patients with active SLE at baseline of the initial study. Biomarker and SLE medication changes were evaluated, and adverse events (AE) were monitored throughout the study.

Results.

Total belimumab exposure over 7 years (double-blind and open-label periods): 1746 patient-years. SLE Responder Index (SRI) response rates at Week 52 in autoantibody-positive patients: placebo, 29%; belimumab, 46% (p < 0.05). In the continuation study, 57% of auto-antibody-positive patients had an SRI response by Year 2 and 65% by Year 7; severe flares occurred in 19% with placebo and 17% with belimumab during the first year, with the annual rate declining to 2%–9% during years 2–7. Anti-dsDNA autoantibodies in patients positive for them at baseline had a progressive decline of 40%–60% from baseline over 2–7 years with belimumab. Corticosteroid use decreased over time with ≥ 50–55% reduction in median dose during years 5–7. Serious and overall annual AE rates, including infections, were generally stable or decreased during 7-year treatment.

Conclusion.

Disease control and safety profile were maintained in patients with active SLE taking belimumab plus standard therapy for up to 7 years. [ClinicalTrials.gov numbers: NCT00071487 and NCT00583362]
Higher Frequency of Peripheral Blood Interleukin 21 Positive Follicular Helper T Cells in Patients with Ankylosing Spondylitis
Authors: Xiao Fei , Zhang Hai-Yu , Liu Yi-Jun , Zhao Ding , Shan Yu-Xing , Jiang Yan-Fang
Published: November 2013

Objective.

The role of follicular Th (TFH) cells remains unclear in the pathogenesis of ankylosing spondylitis (AS). Our study examined the frequency of different subsets of circulating CXCR5+CD4+ T cells in patients with AS before and after receiving therapy.

Methods.

Percentages of peripheral blood inducible costimulator (ICOS)+, programmed death 1 (PD-1)+, and interleukin 21 (IL-21)+ CXCR5+CD4+ T cells in 26 patients with AS and 12 healthy controls (HC) were examined by flow cytometry, and the disease activity of individual patients was measured by Bath AS Disease Activity Index (BASDAI). The concentrations of serum IL-21, IgG, IgA, IgM, and C-reactive protein (CRP) were examined and the values of erythrocyte sedimentation rate (ESR) were measured. The potential association among these measures was analyzed.

Results.

In comparison with that in HC, significantly increased percentages of CXCR5+CD4+, CXCR5+CD4+PD-1+, and CXCR5+CD4+IL-21+, but not CXCR5+CD4+ICOS+ and PD-1+ICOS+CXCR5+CD4+ T cells, and elevated concentrations of serum IL-21 were detected in patients with AS (p = 0.001, p = 0.012, p < 0.001, p = 0.233, p = 0.216, p < 0.001, respectively). Treatment with meloxicam, thalidomide, and etanercept for 1 month significantly reduced percentages of IL-21+CXCR5+CD4+ T cells and concentrations of serum IL-21 (p < 0.001, p < 0.001, respectively), accompanied by significantly minimized disease activity in drug responders, but not in the drug nonresponders. Further, percentages of IL-21+CXCR5+CD4+ T cells were positively correlated with BASDAI in patients (r = 0.6, p = 0.0012) and in the drug-responders 1 month after treatment (r = 0.68, p = 0.005), while the percentages of PD-1+CXCR5+CD4+ T cells were negatively correlated with BASDAI (r = −0.58, p = 0.0018).

Conclusion.

These data suggest that IL-21+CXCR5+CD4+ T cells may be associated with development of AS and that the frequency of IL-21+CXCR5+CD4+ T cells may be a biomarker for evaluation of disease activity and drug responses in patients with AS, particularly in drug-responding patients.
Risk Markers of Juvenile Idiopathic Arthritis-associated Uveitis in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry
Authors: Angeles-Han Sheila T. , Pelajo Christina F. , Vogler Larry B. , Rouster-Stevens Kelly , Kennedy Christine , Ponder Lori , McCracken Courtney , Lopez-Benitez Jorge , Drews-Botsch Carolyn , Prahalad Sampath ,   The CARRA Registry Investigators
Published: November 2013

Objective.

To characterize the epidemiology and clinical course of children with juvenile idiopathic arthritis-associated uveitis (JIA-U) in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry and explore differences between African American (AA) and non-Hispanic white (NHW) children.

Methods.

There were 4983 children with JIA enrolled in the CARRA Registry. Of those, 3967 NHW and AA children were included in this study. Demographic and disease-related data were collected from diagnosis to enrollment. Children with JIA were compared to those with JIA-U. Children with JIA-U were also compared by race.

Results.

There were 459/3967 children (11.6%) with JIA-U in our cohort with a mean age (SD) of 11.4 years (± 4.5) at enrollment. Compared to children with JIA, they were younger at arthritis onset, more likely to be female, had < 5 joints involved, had oligoarticular JIA, and were antinuclear antibody (ANA)-positive, rheumatoid factor (RF)-negative, and anticitrullinated protein antibody-negative. Predictors of uveitis development included female sex, early age of arthritis onset, and oligoarticular JIA. Polyarticular RF-positive JIA subtype was protective. Nearly 3% of children with JIA-U were AA. However, of the 220 AA children with JIA, 6% had uveitis; in contrast, 12% of the 3721 NHW children with JIA had uveitis.

Conclusion.

In the CARRA registry, the prevalence of JIA-U in AA and NHW children is 11.6%. We confirmed known uveitis risk markers (ANA positivity, younger age at arthritis onset, and oligoarticular JIA). We describe a decreased likelihood of uveitis in AA children and recommend further exploration of race as a risk factor in a larger population of AA children.
Effectiveness and Safety of Tocilizumab: Postmarketing Surveillance of 7901 Patients with Rheumatoid Arthritis in Japan
Authors: Koike Takao , Harigai Masayoshi , Inokuma Shigeko , Ishiguro Naoki , Ryu Junnosuke , Takeuchi Tsutomu , Takei Syuji , Tanaka Yoshiya , Sano Yoko , Yaguramaki Hitomi , Yamanaka Hisashi
Published: November 2013

Objective.

An all-patient postmarketing surveillance program was conducted to evaluate the safety and effectiveness of tocilizumab (TCZ) for rheumatoid arthritis (RA) in the real-world clinical setting in Japan.

Methods.

Patients received 8 mg/kg TCZ every 4 weeks and were observed for 28 weeks. Data were collected on patient characteristics, and drug safety and effectiveness.

Results.

A total of 7901 patients were enrolled. Percentages of total and serious adverse events (AE) were 43.9% and 9.6%, respectively. The most common serious AE were infections (3.8%). Logistic regression analysis identified the following risk factors for the development of serious infection: age ≥ 65 years, disease duration ≥ 10 years, previous or concurrent respiratory disease, and concomitant corticosteroid dose > 5 mg/day (prednisolone equivalent). The incidence rate of serious infections in patients with ≥ 3 risk factors was 11.2%, compared with 1.2% for patients without risk factors. The Week 28 rates of 28-joint Disease Activity Score–erythrocyte sedimentation rate remission, Boolean remission, and European League Against Rheumatism (EULAR) Good Response were 47.6%, 15.1%, and 59.4%, respectively. Contributing factors for effectiveness were body weight ≥ 40 kg, less advanced RA, no previous biologics, no concomitant corticosteroids or nonsteroidal antiinflammatory drugs, and low disease activity at baseline. From the benefit-risk balance analysis, patients with a high probability of remission and a low probability of developing serious infection were most likely to have less advanced RA and to have not received biologics previously.

Conclusion.

These data confirm the safety and effectiveness of TCZ in patients with RA in the real-world clinical setting in Japan and identify factors that contribute to the successful use of TCZ for RA.
Chronic Widespread Pain in Patients with Rheumatoid Arthritis and the Relation Between Pain and Disease Activity Measures over the First 5 Years
Authors: Andersson Maria L.E. , Svensson Björn , Bergman Stefan
Published: November 2013

Objective.

To study the prevalence of chronic widespread pain (ChWP), chronic regional pain (ChRP), and fibromyalgia in patients with early rheumatoid arthritis (RA) followed for 5 years after inclusion, and to study the effect of pain on measures of disease activity and function.

Methods.

A questionnaire was sent to 1910 patients participating in the Better Anti-Rheumatic Pharmacotherapy study. The responders (73%) were divided into 3 groups according to the reported pain duration and distribution — patients having no chronic pain (NChP), ChWP, and ChRP. Outcome measures were the 28-joint Disease Activity Score (DAS28), the Health Assessment Questionnaire (HAQ), and C-reactive protein (CRP).

Results.

Thirty-four percent of respondents reported ChWP, 46% ChRP, and 20% NChP. Patients reporting ChWP were more often women and had more pain and tender joints at inclusion. From 6 months to 5 years of followup, mean DAS28, visual analog scale (VAS) pain, VAS global health, and HAQ were significantly higher in the ChWP group than in the other groups. However, all groups showed a similar pattern in swollen joint count, erythrocyte sedimentation rate (ESR), and CRP. From 12 months the ChWP group was treated with prednisolone to a greater extent than the ChRP group, and it had a rate of treatment with disease-modifying antirheumatic drugs similar to that of the ChRP group.

Conclusion.

ChWP is a common feature in RA, more associated with high values for variables related to pain such as the DAS28 and HAQ than to indicators of ongoing inflammation such as swollen joint count, ESR, and CRP. Patients with ChWP should be identified so that adequate treatment also of the noninflammatory pain may be instituted.
Clinical Investigation of Nontuberculous Mycobacterial Lung Disease in Japanese Patients with Rheumatoid Arthritis Receiving Biologic Therapy
Authors: Yamakawa Hideaki , Takayanagi Noboru , Ishiguro Takashi , Kanauchi Tetsu , Hoshi Toshiko , Sugita Yutaka
Published: November 2013

Objective.

To review patients with rheumatoid arthritis (RA) receiving biologic therapy following a diagnosis of nontuberculous mycobacterial (NTM) lung disease and to evaluate disease deterioration according to clinical and radiological features and anti-NTM therapy.

Methods.

We retrospectively analyzed medical records of 11 human immunodeficiency virus-negative patients with RA (median age, 64 years) receiving biologic therapy following diagnosis of NTM lung disease.

Results.

NTM species includedMycobacterium aviumcomplex in 9 patients (81.8%) andM. gordonaein 2 (18.2%). Underlying respiratory disease was present in 6 patients (54.5%), and most (81.8%) had radiographic features of nodular/bronchiectatic disease. Extent of NTM disease was 1–2 pulmonary lobes in 6 patients (54.5%), 3–4 lobes in 5 patients (45.5%), and 5–6 lobes in none. The results of radiological evaluations were unchanged or improved in 7 patients (63.6%) and worsened in 4 (36.4%). Radiological outcome was worse in patients with poor RA control despite their receiving biologic therapies for RA. Two of 3 patients receiving anti-NTM therapy as initial management for NTM improved, and 1 worsened. Three of 4 patients with worsened radiological outcome had high erythrocyte sedimentation rate (> 50 mm/h).

Conclusion.

Radiological deterioration was not observed in the majority of patients with RA receiving biologic therapy with NTM lung disease, and radiological outcome of pulmonary NTM was favorable in some patients undergoing anti-NTM therapy. Further studies focusing on disease deterioration according to biologic therapy received during NTM followup are warranted to determine appropriate treatment of RA patients with NTM lung disease.
Treatment of Refractory Takayasu Arteritis with Tocilizumab: 7 Italian Patients from a Single Referral Center
Authors: Tombetti Enrico , Franchini Stefano , Papa Maurizio , Sabbadini Maria Grazia , Baldissera Elena
Published: November 2013

Objective.

The aim of our study was to evaluate the safety and the efficacy of tocilizumab (TCZ) for refractory Takayasu arteritis (TA).

Methods.

We retrospectively assessed the outcome of blocking interleukin (IL)-6 with TCZ in 7 consecutive patients with refractory TA using a combination of clinical and imaging assessment.

Results.

During a median followup visit at 14 months, 4 patients taking TCZ [including 2 nonresponders to tumor necrosis factor (TNF) inhibitors] achieved clinical response, suggesting a nonredundant role for IL-6 in TA. Inflammatory markers normalized in all patients treated with TCZ. However, vascular progression occurred in 4 patients, suggesting the involvement of other inflammatory pathways and confirming the limitations of erythrocyte sedimentation rate and C-reactive protein for disease activity assessment while taking TCZ. Three patients experienced adverse events and 2 suspended TCZ.

Conclusion.

TCZ may be effective in a subset of patients with refractory TA, even in cases of unresponsiveness to TNF inhibitors. Inflammatory markers are not valid markers of TA activity on TCZ. Further studies are needed to confirm these preliminary observations.
Correlation of Radiographic Progression with the Cumulative Activity of Synovitis Estimated by Power Doppler Ultrasound in Rheumatoid Arthritis: Difference Between Patients Treated with Methotrexate and Those Treated with Biological Agents
Authors: Ikeda Kei , Nakagomi Daiki , Sanayama Yoshie , Yamagata Mieko , Okubo Ayako , Iwamoto Taro , Kawashima Hirotoshi , Takahashi Kentaro , Nakajima Hiroshi
Published: November 2013

Objective.

Our prospective study aimed to demonstrate that the cumulative synovial power Doppler (PD) ultrasound scores correlate with radiographic progression better than conventional measures in patients with rheumatoid arthritis (RA). We also investigated the difference between antirheumatic agents.

Methods.

Sixty-nine patients with RA who had recently received either methotrexate (MTX; n = 23), tumor necrosis factor (TNF) antagonists (n = 28), or tocilizumab (TCZ; n = 18) were enrolled. Patients underwent clinical, laboratory, and ultrasonographic assessment at baseline, 12 weeks, and 24 weeks. Radiographic damage was evaluated using van der Heijde modified total Sharp score (TSS) at baseline and 24 weeks.

Results.

Fifty-seven patients continued the same treatment regimen for 24 weeks and completed the study, and 21 patients (36.8%) showed radiographic progression during the study period. In all patients, ΔTSS significantly correlated both with cumulative 28-joint Disease Activity Score–C-reactive protein (DAS28-CRP; ρ = 0.342, p = 0.009) and cumulative total PD scores (ρ = 0.357, p = 0.006). In MTX-treated patients, cumulative total PD scores significantly correlated with ΔTSS (ρ = 0.679, p = 0.004), whereas cumulative DAS28-CRP did not (ρ = 0.487, p = 0.056). However, cumulative total PD scores did not correlate with ΔTSS in TNF antagonist–treated or TCZ-treated patients.

Conclusion.

Our data confirm the evidence that synovial PD activity more accurately reflects active synovial inflammation (which actually causes joint destruction) than do conventional measures in patients treated with MTX. Our data also indicate that TNF antagonists can inhibit short-term radiographic progression in the presence of active synovitis.
COMP-C3b Complexes in Rheumatoid Arthritis with Severe Extraarticular Manifestations
Authors: Happonen Kaisa E. , Saxne Tore , Jacobsson Lennart , Sturfelt Gunnar , Rönnelid Johan , Mollnes Tom Eirik , Heinegård Dick , Turesson Carl , Blom Anna M.
Published: November 2013

Objective.

To investigate biomarker patterns in rheumatoid arthritis (RA) with extraarticular manifestations.

Methods.

Cartilage oligomeric matrix protein (COMP), COMP-C3b, and soluble terminal complement complexes (sTCC) were measured by ELISA.

Results.

COMP-C3b levels were higher in patients with RA than in healthy controls and lower in extraarticular RA (ExRA) than in RA controls. In patients with ExRA, sTCC levels were higher than in RA controls, and correlated inversely with serum COMP-C3b levels in the ExRA group.

Conclusion.

Patients with ExRA had lower levels of COMP-C3b. This may be a consequence of complement consumption or a lower potential for COMP from these patients to activate complement.
Ultrasound and Magnetic Resonance Imaging in the Evaluation of Psoriatic Dactylitis: Status and Perspectives
Authors: Bakewell Catherine J. , Olivieri Ignazio , Aydin Sibel Z. , Dejaco Christian , Ikeda Kei , Gutierrez Marwin , Terslev Lene , Thiele Ralf , D’Agostino Maria Antionetta , Kaeley Gurjit S.
Published: November 2013

Objective.

Dactylitis, a characteristic feature of the spondyloarthropathies, occurs in up to 48% of patients with psoriatic arthritis (PsA). No clear consensus on the underlying components and pathogenesis of dactylitis exists in the literature. We undertook a systematic review of ultrasound (US) and magnetic resonance imaging (MRI) literature to better define imaging elements that contribute to the dactylitic digit seen in PsA. Our objectives were to determine first the level of homogeneity of each imaging modality’s definition of the components of dactylitis, and second, to evaluate the metric properties of each imaging modality according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) filter.

Methods.

Searches were performed in PUBMED and EMBASE for articles pertaining to MRI, US, and dactylitis. Data regarding the reported features of dactylitis were collected and categorized, and the metrological qualities of the studies were assessed.

Results.

The most commonly described features of dactylitis were flexor tendon tenosynovitis and joint synovitis (90%). Extratendinous soft tissue thickening and extensor tendonitis were described nearly equally as being present and absent. Discrepancy exists as to whether entheses proper contribute to the etiology of dactylitis. An increasing number of studies categorize abnormalities in several tissue compartments including the soft tissue, tendon sheaths, and joints, as well as ligaments.

Conclusion.

The understanding of which tissues contribute to dactylitic inflammation has evolved. However, there is a lack of literature regarding the natural history of these abnormalities. This systematic review provides guidance in defining elementary lesions that may discriminate dactylitic digits from normal digits, leading to development of a composite measure of activity and severity of dactylitis.
Selecting Magnetic Resonance Imaging (MRI) Outcome Measures for Juvenile Idiopathic Arthritis (JIA) Clinical Trials: First Report of the MRI in JIA Special Interest Group
Authors: Hemke Robert , Doria Andrea S. , Tzaribachev Nikolay , Maas Mario , van der Heijde Désirée M.F.M , van Rossum Marion A.J.
Published: November 2013

Recent advances in magnetic resonance imaging (MRI) techniques have substantially improved the evaluation of joint pathologies in juvenile idiopathic arthritis (JIA). Because of the current availability of highly effective antirheumatic therapies and the unique and useful features of MRI, there is a growing need for an accurate and reproducible MRI assessment scoring system for JIA, such as the rheumatoid arthritis MRI Scoring (RAMRIS) for patients with rheumatoid arthritis (RA). To effectively evaluate the efficacy of treatment in clinical research trials, we need to develop and validate scoring methods to accurately measure joint outcomes, standardize imaging protocols for data acquisition and interpretation, and create imaging atlases to differentiate physiologic and pathologic joint findings in childhood and adolescence. Such a standardized, validated, JIA-MRI scoring method could be used as an outcome measure in clinical trials.
Verification of Wave Measurement Systems
Authors: Luther Mark E. , Meadows Guy , Buckley Earle , Gilbert Sherryl A. , Purcell Heidi , Tamburri Mario N.
Published: November 2013

AbstractGiven the societal importance of reliable and accurate ocean observations, the wave monitoring community (including academic researchers, agency scientists, resource managers, and representatives from wave instrument manufacturers) came together to develop a set of
protocols for the test and evaluation of wave measurement systems in support of the 2009 National Operational Wave Observation Plan. These protocols are focused on a wide range of wave measurement instruments and their respective performance in successfully recovering the “First-5”
Fourier components of the incident wave field. Performance is determined by comparing each system’s output with a verifiable reference method over a predetermined range of wave frequencies. It is recommended that permanent wave test facilities are created on the West Coast (Monterey
Bay, CA—deep water) and the East Coast (Duck, NC—shallow water) for continued evaluations of existing and new technologies. It was recognized that no absolute standard exists for the determination of the “First-5” across all spatial domains. Therefore, it was agreed
that the Directional Waverider DWR-MkIII system was the best available reference/standard for the deep and intermediate water wave evaluations as verified by the laser array (LASAR) at the ConocoPhillips Ekofisk offshore platform complex in the North Sea. The long linear array at the U.S.
Army Corps of Engineers’ Field Research Facility could be used as the standard for shallow water wave evaluations. Finally, given the significance of wave measurements, an appropriate level of quality assurance and quality control procedures must be included as part of any test and evaluation
effort. The details of the proposed protocols for the verification of wave measurement systems are described.
The Future of Marine Propulsion: “Reading the Propulsion Crystal Ball”
Authors: Tangora Michael
Published: November 2013

AbstractThe marine industry is headed into a period of uncertainty as both environmental restrictions and rising fuel prices simultaneously converge unlike any time in its past. Yet at the same time, innovations in propulsion solutions have allowed the industry to keep pace
with demands thus far, as the demand signal continues for both efficient propulsion designs as well as lower overall emissions. The growing calls for environmental compliance, and its origins will be examined, as well as solutions that will reduce propulsion emissions. New regulations and
fuels with lower sulfur content will require reconfiguration of the propulsion plants. This paper primarily discusses both the background of the challenges that the industry will be facing as well as available solutions. Both the marine industry as well as the military will be reviewed.
Extended-Range Undersea Laser Imaging: Current Research Status and a Glimpse at Future Technologies
Authors: Dalgleish Fraser R. , Vuorenkoski Anni K. , Ouyang Bing
Published: November 2013

AbstractRecent advancements in obtaining visibility of undersea objects at extended ranges in coastal and oceanic waters are reviewed for the years 2009 to present. The paper focuses on the latest techniques that are utilized to reduce the undesirable effects of scattering, mainly due to suspended particulate within the imaging volume, leading to the loss of contrast and blurring characteristic of undersea optical images produced over long ranges. Several recent sets of experimental results obtained using both benchtop laboratory development systems as well as field-deployable prototypes of new system concepts are presented, with observed performance attributes being discussed. Simulation studies that make use of accurate radiative transfer physical models to enable design and operation of new system concepts within a turbid water environment are also presented. Finally, this paper includes a description and results from an extended-range laser system that has reached a level of packaging and automation necessary to be available as a commercial product.
Advantages of Natural Propulsive Systems
Authors: Fish Frank E.
Published: November 2013

AbstractThe screw propeller has been the mainstay of marine propulsion, but new developments in biomimetic propulsion can provide advantages in terms of speed, maneuverability, efficiency, and stealth. The diversity of aquatic animals provides designs for drag-based paddling and lift-based oscillatory hydrofoils that can be incorporated into engineered propulsive systems for enhanced performance. While the screw propeller will remain the prominent propulsive device, the choice of alternative biomimetic propulsive systems will be dependent on particular applications, where the specifications dictate improved performance criteria.
State of Technology in Autonomous Underwater Gliders
Authors: Wood Stephen L. , Mierzwa Cheryl E.
Published: November 2013

AbstractOver the last few decades, a range of instruments and vehicles have been used to monitor the oceans. One example is the use of autonomous underwater vehicles to perform ocean surveys, and within this group, autonomous underwater gliders have made their mark. Gliders
enable the scientist to make extended complex studies on topics such as the effect of metals, pesticides, and nutrients on fish abundance, reproductive success, and ability to feed or on contaminants such as chemicals or biological toxins that are transported in particulate form and may become
incorporated into living organisms (plankton, bivalves, and fish) or become deposited in bottom sediments. With these vehicles, the scientist or environmentalist can detect hazardous substances in the ocean such as chemicals from an oil spill or toxic algae such as red tide.
Synthetic Aperture Sonar Technology Review
Authors: Hansen Roy Edgar
Published: November 2013

AbstractSonar imaging has numerous applications in the underwater domain. High-resolution sonar images are useful in marine research, underwater construction work, offshore oil and gas, search for objects, and in the military sector. Common in many applications is the desire
for higher resolution, better image quality, longer range, and smaller hardware footprint. Synthetic aperture sonar (SAS) technology can improve resolution and/or range substantially compared to traditional technology. Recent developments in SAS make this technology more available now. This
paper gives a review of SAS technology and shows example of SAS applications. The paper lists the current state-of-the-art and the future trends of SAS.
Review of Deep Ocean Manned Submersible Activity in 2013
Authors: Kohnen William
Published: November 2013

AbstractThe world of manned underwater vehicles (MUV) in 2013 counts a total of 95 active submersibles used for ocean research, tourism, and commercial, leisure, and security applications. The MUV industry safety record remains pristine, with not a single incident involving
loss of life in over 40 years. The paper reviews the state and future directions for the world’s deepest ocean research submersibles. In 2012 and 2013, the world of deep research submersibles saw dramatic advances, reaching full ocean depth for the first time in more than 50 years. The
record of the world’s deepest submersible held by Japan’s Shinkai 6500, rated to 6,500 m depth, for almost 25 years was surpassed by China’s 10-year development project of the Jiaolong submersible, rated to 7,000 m. The Jiaolong successfully completed
its multiyear testing program, achieving full design depth in June 2012. This record feat was eclipsed, however, by the surprise disclosure and full ocean depth dive by James Cameron’s Deepsea Challenger, diving to a depth of 10,908 m in the Mariana Trench just months earlier.
This depth had not been reached since the historic dive of the bathyscaphe Trieste in 1960, and brings new energy for several national organizations to develop full ocean depth submersibles. There are today a total of 14 national and commercial submersibles capable of diving 1,000 m
or deeper, offering a wide range of services. This also provides a global network of rescue capability with locations in the United States, China, Japan, Russia, France, Spain, Canada, and Portugal.
Homeostasis of Human NK Cells Is Not IL-15 Dependent
Authors: Lebrec Herve , Horner Michelle J. , Gorski Kevin S. , Tsuji Wayne , Xia Dong , Pan Wei-Jian , Means Gary , Pietz Greg , Li Nianyu , Retter Marc , Shaffer Kathy , Patel Neha , Narayanan Padma K. , Butz Eric A.
Published: November 2013

IL-15 is a proinflammatory cytokine that plays an important role in the development and activation of NK cells and is a potential target for inflammatory disease therapy. Studies conducted in IL-15- and IL-15R knockout mice identified IL-15 as an important cytokine for NK cell homeostasis. Consistent with this information derived from genetically modified mice, we demonstrated that neutralizing IL-15 with a mouse anti-mouse IL-15 mAb (M96) depletes C57BL/6 mouse NK cells. An mAb directed against macaque IL-15 (Hu714MuXHu) was manufactured and demonstrated to block IL-15–induced activation of nonhuman primate (NHP) NK cells in vitro. Neutralization of macaque IL-15 by parenteral administration of Hu714MuXHu reduces (>95%) circulating NK cell counts in NHPs. A blocking mAb directed against human IL-15 (huIL-15; AMG 714) was manufactured. Unexpectedly, when human subjects were treated with the blocking anti–IL-15 Ab AMG 714 in clinical trials, no reductions in circulating NK cell counts were observed despite achieving significantly higher exposures than the levels of Hu714MuXHu needed to cause NK cell count reductions in NHPs in vivo. Both AMG 714 and Hu714MuXHu are able to block huIL-15 activity in a human T cell blast proliferation and IFN-γ production assay. Both Abs block huIL-15–mediated Stat5 activation and CD69 expression in human NK cells. Collectively, these results demonstrate that NK cell homeostasis is obligatorily dependent upon IL-15 in both mice and NHPs, but that IL-15 is dispensable for maintenance of circulating human NK cells.
The Road to Memory: An Early Rest for the Long Journey
Authors: Ho Liam Pock , Yit Pui San , Ng Lee Hui , Linn Yeh Ching , Zhao Yi , Sun Li , Ling Khoon Lin , Chai Koh Mickey Boon , Monica Shih Meng-Chun , Li Shang , Wang Xue Ying , Tien Sim Leng , Goh Yeow Tee
Published: November 2013

Central memory T lymphocytes were reported to develop after acute but not chronic infection, which prompted this feasibility study on generating long-term CD8 T cells ex vivo, by applying a culture condition that simulates an acute infection. During 35 d of culture, naive T cells (CD45RA+, CD127+, CCR7+, CD62L+, CXCR3+) first developed into effector T cells (CD45RA+/−, CD127+/−, CCR7+/−, CD62L+, CXCR3+), followed by three intermediate stages: intermediate T cells 1 (CD45RO+, CD127+/−, CCR7+, CD62L+, CXCR3+), intermediate T cells 2 (CD45RO+, CD127−, CCR7−, CD62L+, CXCR3+), and intermediate T cells 3 (CD45RO+/−, CD127+, CCR7+, CD62L−, CXCR3+) before reverting to stable CD45RA+ central memory T cells (CD45RA+, CD127+, CCR7+, CD62L+, CXCR3+). If both anti-CD3 and the inflammatory milieu persisted beyond day 10, intermediate T cells 2 gradually developed into effector memory T cells (CD45RO+, CD127−, CCR7−, CD62L−, CXCR3+). Furthermore, intermediate T cells 2 or effector memory T cells, when cultured in persistent inflammatory cytokines devoid of anti-CD3, were converted to central memory T cells (CD45RO+, CCR7+, CD62L+). Overall, these results support ex vivo memory-like T lymphocyte production and favor a developmental pathway including both divergent and linear relationships.
Mannose Receptor 1 Mediates Cellular Uptake and Endosomal Delivery of CpG-Motif Containing Oligodeoxynucleotides
Authors: Moseman Annie Park , Moseman E. Ashley , Schworer Stephen , Smirnova Irina , Volkova Tatyana , von Andrian Ulrich , Poltorak Alexander
Published: November 2013

Recognition of microbial components is critical for activation of TLRs, subsequent innate immune signaling, and directing adaptive immune responses. The DNA sensor TLR9 traffics from the endoplasmic reticulum to endolysosomal compartments where it is cleaved by resident proteases to generate a competent receptor. Activation of TLR9 by CpG-motif containing oligodeoxynucleotides (CpG ODNs) is preceded by agonist endocytosis and delivery into the endolysosomes. The events that dictate this process remain largely unknown; furthermore, it is unclear whether the receptors involved in mediating uptake of exogenous DNA are conserved for both naturally derived pathogenic DNA and synthetic ODNs. In this study, we report that peritoneal macrophages from a wild-derived inbred mouse strain, MOLF/Ei, are hyporesponsive to CpG ODN but are fully responsive to bacterial DNA, thus implying that microbial recognition is not fully recapitulated by a synthetic analog. To identify the gene responsible for the CpG ODN defect, we have performed genome-wide linkage analysis. Using N2 backcross mice, we mapped the trait with high resolution to a single locus containing Mrc1 as the gene conferring the trait. We show that mannose receptor 1 (MRC1; CD206) is involved in CpG ODN uptake and trafficking in wild-derived MOLF/Ei peritoneal macrophages. Furthermore, we show that other strains of wild-derived mice also require MRC1 for CpG-induced cytokine responses. These findings reveal novel functions for MRC1 and demonstrate that wild-derived mice are important and indispensable model for understanding naturally occurring regulators of inflammatory responses in innate immune pathways.
Exosomes Secreted by Human Placenta Carry Functional Fas Ligand and TRAIL Molecules and Convey Apoptosis in Activated Immune Cells, Suggesting Exosome-Mediated Immune Privilege of the Fetus
Authors: Stenqvist Ann-Christin , Nagaeva Olga , Baranov Vladimir , Mincheva-Nilsson Lucia
Published: November 2013

Apoptosis is crucially important in mediating immune privilege of the fetus during pregnancy. We investigated the expression and in vitro apoptotic activity of two physiologically relevant death messengers, the TNF family members Fas ligand (FasL) and TRAIL in human early and term placentas. Both molecules were intracellularly expressed, confined to the late endosomal compartment of the syncytiotrophoblast, and tightly associated to the generation and secretion of placental exosomes. Using immunoelectron microscopy, we show that FasL and TRAIL are expressed on the limiting membrane of multivesicular bodies where, by membrane invagination, intraluminal microvesicles carrying membranal bioactive FasL and TRAIL are formed and released in the extracellular space as exosomes. Analyzing exosomes secreted from placental explant cultures, to our knowledge, we demonstrate for the first time that FasL and TRAIL are clustered on the exosomal membrane as oligomerized aggregates ready to form death-inducing signaling complex. Consistently, placental FasL- and TRAIL-carrying exosomes triggered apoptosis in Jurkat T cells and activated PBMC in a dose-dependent manner. Limiting the expression of functional FasL and TRAIL to exosomes comprise a dual benefit: 1) storage of exosomal FasL and TRAIL in multivesicular bodies is protected from proteolytic cleavage and 2) upon secretion, delivery of preformed membranal death molecules by exosomes rapidly triggers apoptosis. Our results suggest that bioactive FasL- and TRAIL-carrying exosomes, able to convey apoptosis, are secreted by the placenta and tie up the immunomodulatory and protective role of human placenta to its exosome-secreting ability.