bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of extrusion process, type and content of clays, and foaming process on the clay exfoliation in HMS PP composites
Authors: Laguna‐Gutierrez Ester , Van Hooghten Rob , Moldenaers Paula , Angel Rodriguez‐Perez Miguel 
Published: August 2015

ABSTRACTThe use of a high melt strength polypropylene (HMS PP) matrix reinforced with layered clays could be very useful to improve the properties of materials produced with processes involving melt stretching, like foaming. The control of the particles structure, that is, the degree of exfoliation and the clay distribution in the polymeric matrix, is the key to achieve the desired properties. In this study, the effects of the extrusion process, the clay type and content, and the foaming process on the morphology of different HMS PP based composites are studied. Both, natural and organomodified clays were used. The extrusion process has a negative effect in the composites containing natural clays as their interlayer distance decreases as the number of extrusion cycles increases. On the contrary, this process improves the intercalation of the organomodified clays. However, in both composites the interlayer spacing decreases when the clay content increases. While a percolated network is formed in the composites containing organomodified clays, no network is formed with the natural clays. Finally, the effect of the foaming process has also been analyzed. The Improved Compression Moulding (ICM) route was used to produce the foamed materials. This technique subjects the materials only to a temperature and a pressure gradient without applying any other external forces that could contribute to the clay exfoliation. In this way, only the effects of foaming and melt stretching are observed. In both composites, an increase in the interlayer distance is observed when the materials are foamed. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42828.
Convicts and commodities: An archaeological approach to the economic value of the Western Australian penal system
Authors: Haast Alyce 
Published: August 2015

ABSTRACTThe introduction of the convict system in 1850 into the Western Australian (WA) economy resulted in a large injection of capital into the colony, the dissemination of which cannot be overlooked when considering the transformative effect of the convict system. This injection resulted from the purchase of goods and services by the penal system that ultimately transferred money from the British Crown into the local market. For this paper, historical and archaeological data was used to develop an understanding of the breakdown of spending by the penal system, and to consider how the circumstance of individual aspects of the penal system impacted purchasing choices, and subsequently benefitted the local market. Using artefacts recovered from two sites within Fremantle Prison, one representing institutional purchases and the other relating to a wage earner, it was possible the test the variation in economic impact of spending given institutional circumstance. By considering whether purchases represented local commodities or imports, it was possible to see how capital transferred into the local economy and how much of that spending leaked out through imports. In doing this, the analysis highlighted the varying benefit of the capital injected by the penal system related to circumstance and the value of considering the penal system as an elaborate entity.
Brief Report: Cartilage Thickness Change as an Imaging Biomarker of Knee Osteoarthritis Progression: Data From the Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium
Authors: Eckstein F. , Collins J. E. , Nevitt M. C. , Lynch J. A. , Kraus V. B. , Katz J. N. , Losina E. , Wirth W. , Guermazi A. , Roemer F. W. , Hunter D. J. ,   for the FNIH OA Biomarkers Consortium
Published: August 2015

ObjectiveTo investigate the association of cartilage thickness change over 24 months, as determined by magnetic resonance imaging (MRI), with knee osteoarthritis (OA) progression at 24–48 months.MethodsThis nested case–control study included 600 knees with a baseline Kellgren/Lawrence (K/L) grade of 1–3 from 600 Osteoarthritis Initiative (OAI) participants. Case knees (n = 194) had both medial tibiofemoral radiographic joint space loss (≥0.7 mm) and a persistent increase in the Western Ontario and McMaster Universities Osteoarthritis Index pain score (≥9 on a 0–100 scale) 24–48 months from baseline. Control knees (n = 406) included 200 with neither radiographic nor pain progression, 103 with radiographic progression only, and 103 with pain progression only. Medial and lateral femorotibial cartilage was segmented from sagittal 3T MRIs at baseline, 12 months, and 24 months. Logistic regression was used to assess the association of change in cartilage thickness, with a focus on the central medial femorotibial compartment, and OA progression.ResultsCentral medial femorotibial compartment thickness loss was significantly associated with case status, with an odds ratio (OR) of 1.9 (95% confidence interval [95% CI] 1.6–2.3) (P < 0.0001). Association with case status reached P < 0.05 for both the central femur (OR 1.8 [95% CI 1.5–2.2]) and the central tibia (OR 1.6 [95% CI 1.3–1.9]). Lateral femorotibial compartment cartilage thickness loss, in contrast, was not significantly associated with case status. A reduction in central medial femorotibial compartment cartilage thickness was strongly associated with radiographic progression (OR 4.0 [95% CI 2.9–5.3]; P < 0.0001) and only weakly associated with pain progression (OR 1.3 [95% CI 1.1–1.6]; P < 0.01).ConclusionOur findings indicate that loss of medial femorotibial cartilage thickness over 24 months is associated with the combination of radiographic and pain progression in the knee, with a stronger association for radiographic progression.
Latent Cytomegalovirus Infection in Rheumatoid Arthritis and Increased Frequencies of Cytolytic LIR‐1+CD8+ T Cells
Authors: Rothe Kathrin , Quandt Dagmar , Schubert Kristin , Rossol Manuela , Klingner Maria , Jasinski‐Bergner Simon , Scholz Roger , Seliger Barbara , Pierer Matthias , Baerwald Christoph , Wagner Ulf 
Published: August 2015

ObjectiveLeukocyte immunoglobulin‐like receptor 1 (LIR‐1) is up‐regulated by cytomegalovirus (CMV), which in turn, has been associated with premature aging and more severe joint disease in patients with rheumatoid arthritis (RA). The aim of this study was to investigate the expression and functional significance of LIR‐1 in CMV‐positive RA patients.MethodsWe determined the phenotype, cytolytic potential, CMV‐specific proliferation, and HLA–G–triggered, LIR‐1–mediated inhibition of interferon‐γ secretion of LIR‐1+ T cells in RA patients and healthy controls.ResultsWe found increased frequencies of CD8+ T cells with CMV pp65–specific T cell receptors in CMV‐positive RA patients as compared to CMV‐positive healthy controls. CMV‐specific CD8+ T cells in these patients were preferentially LIR‐1+ and exhibited a terminally differentiated polyfunctional phenotype. The numbers of LIR‐1+CD8+ T cells increased with age and disease activity, and showed high levels of reactivity to CMV antigens. Ligation of LIR‐1 with soluble HLA–G molecules in vitro confirmed an inhibitory role of the molecule when expressed on CD8+ T cells in RA patients.ConclusionWe propose that latent CMV infection in the context of a chronic autoimmune response induces the recently described “chronic infection phenotype” in CD8+ T cells, which retains anti‐infectious effector features while exhibiting autoreactive cytolytic potential. This response is likely dampened by LIR‐1 to avoid overwhelming immunopathologic changes in the setting of the autoimmune disease RA. The known deficiency of soluble HLA–G in RA and the observed association of LIR‐1 expression with disease activity suggest, however, that LIR‐1+ T cells are insufficiently controlled in RA and are still likely to be involved in the pathogenesis of the disease.
Sample Size Calculations for Detecting Disease‐Modifying Osteoarthritis Drug Effects on Knee Replacement Incidence in Clinical Trials: Data From the Osteoarthritis Initiative
Authors: Ried Janina S. , Flechsenhar Klaus , Bartnik Eckart , Crowther Daniel , Dietrich Axel , Eckstein Felix 
Published: August 2015

ObjectiveTo evaluate the extent to which the current designs of clinical trials in knee osteoarthritis (OA) permit detection of a therapeutic effect of disease‐modifying OA drugs (DMOADs) on the incidence of knee replacement, and to provide estimates of the required sample sizes.MethodsWe selected distinct subcohorts of the Osteoarthritis Initiative (OAI), based on available information on eligibility criteria for clinical knee OA trials (ClinicalTrials.gov) and additional subcohorts stratified for age, sex, and the severity of radiographic OA. The observed incidence of knee replacement in these OAI subcohorts was used to estimate the expected incidence of knee replacement in the control group of a clinical trial. Based on this estimate, the sample sizes required to detect hypothetical treatment effects on the incidence of knee replacement were calculated, assuming observation periods of 2, 5, or 7 years.ResultsThe cumulative knee replacement incidence rates in the OAI subcohorts ranged from 0.9% to 12.9%. The corresponding sample sizes required to detect 50% improvement by the DMOAD, with a power of 80% and 95% confidence, were 5,459 and 362, respectively. Including only women with advanced age and radiographic OA increased the incidence of knee replacement and decreased the required sample size.ConclusionThe sample sizes that are commonly used in clinical trials do not enable the effects of a DMOAD on incident knee replacement to be detected with sufficient power and confidence. The estimated incidence rates of knee replacement and the corresponding sample sizes are important for informing the design of trials for disease course–modifying effects as well as for socioeconomic evaluation of a DMOAD in terms of preventing knee replacement.
Takayasu Arteritis and Pregnancy
Authors: Comarmond C. , Mirault T. , Biard L. , Nizard J. , Lambert M. , Wechsler B. , Hachulla E. , Chiche L. , Koskas F. , Gaudric J. , Cluzel P. , Messas E. , Resche‐Rigon M. , Piette J. C. , Cacoub P. , Saadoun D. ,   for the French Takayasu Network
Published: August 2015

ObjectiveTo assess the relationship between Takayasu arteritis (TAK) and pregnancy outcome.MethodsThis study included 240 pregnancies in 96 patients fulfilling the American College of Rheumatology 1990 criteria for the classification of TAK and/or the 1994 Chapel Hill Consensus Conference nomenclature/criteria for vasculitis. We analyzed obstetric and maternal outcomes in women who were pregnant before and/or at the same time as or after TAK diagnosis. We assessed factors associated with complicated pregnancy.ResultsOne hundred forty‐two pregnancies occurred in 52 patients before TAK diagnosis (median age at pregnancy 26 years [interquartile range 23–30 years]), and 98 pregnancies occurred in 52 patients concomitant with or after TAK diagnosis (median age at pregnancy 28 years [interquartile range 26–31 years]). Pregnancies concomitant with or after TAK diagnosis had a 13‐fold higher rate of obstetric complications compared to pregnancies before TAK diagnosis (odds ratio 13 [95% confidence interval 5–33], P < 0.0001). TAK was associated with a 40% frequency of obstetric complications, including preeclampsia/eclampsia (24 pregnancies [24%]), premature delivery (8 pregnancies [8%]), and intrauterine fetal growth restriction or death (5 pregnancies [5%]). Maternal complications of TAK occurred during 39% of pregnancies and included mainly new‐onset or worsening hypertension (26 pregnancies [27%]). In multivariate analysis, smoking (odds ratio 6.15 [95% confidence interval 1.31–28.8]) and disease activity of TAK (a National Institutes of Health score of >1) (odds ratio 28.7 [95% confidence interval 7.89–104.7]) were independently associated with obstetric and maternal complications.ConclusionTAK negatively affects pregnancy outcomes. Disease activity increases the risk of obstetric and maternal complications, mainly due to arterial hypertension.
Type I Interferon Inhibition of MicroRNA‐146a Maturation Through Up‐Regulation of Monocyte Chemotactic Protein–Induced Protein 1 in Systemic Lupus Erythematosus
Authors: Qu Bo , Cao Jianchang , Zhang Feifei , Cui Huijuan , Teng Jialin , Li Jia , Liu Zheng , Morehouse Chris , Jallal Bahija , Tang Yuanjia , Guo Qiang , Yao Yihong , Shen Nan 
Published: August 2015

ObjectiveSystemic lupus erythematosus (SLE) is characterized by the uncontrolled production of inflammatory cytokines, among which type I interferon (IFN) is recognized as a crucial pathogenic factor. The expression of microRNA‐146a (miR‐146a) is reduced in the white blood cells of SLE patients and accounts for their overactivated inflammatory responses. However, the mechanism of the reduction of miR‐146a is still not fully understood. This study was undertaken to test whether the key pathogenic cytokine, type I IFN, is responsible for the dysregulation of miR‐146a in SLE.MethodsGene and protein expression was measured in all cells by reverse transcription–quantitative polymerase chain reaction, Northern blotting, or Western blotting. In THP‐1 cells, expression of monocyte chemotactic protein–induced protein 1 (MCPIP‐1) was knocked down with a lentivirus encoding a short hairpin RNA targeting MCPIP1. The cells were pretreated with type I IFN and assessed for gene expression levels of miR‐146a. White blood cells from patients with SLE were analyzed for the expression of the IFN‐inducible genes MCPIP1 and miR‐146a, and the gene expression data were compared for correlation.ResultsPretreatment of THP‐1 cells with type I IFN attenuated the induction of miR‐146a posttranscriptionally, by down‐regulating the expression of pre‐miR‐146a but not pri‐miR‐146a or its original unspliced transcript. Expression of MCPIP‐1, which was enhanced by type I IFN, was found to be responsible for the inhibition of miR‐146a. In white blood cells from patients with SLE, MCPIP1 expression was elevated, and its expression correlated positively with the IFN score and negatively with the miR‐146a transcript level.ConclusionType I IFN inhibits the maturation of miR‐146a through the up‐regulation of MCPIP‐1, and thus contributes to the uncontrolled inflammation and excessive inflammatory gene expression in SLE.
Rate and Clinical Presentation of Macrophage Activation Syndrome in Patients With Systemic Juvenile Idiopathic Arthritis Treated With Canakinumab
Authors: Grom Alexei A. , Ilowite Norman T. , Pascual Virginia , Brunner Hermine I. , Martini Alberto , Lovell Daniel , Ruperto Nicolino ,   for the Paediatric Rheumatology International Trials Organisation and the Pediatric Rheumatology Collaborative Study Group, Leon Karolynn , Lheritier Karine , Abrams Ken 
Published: August 2015

ObjectiveIn pivotal trials, canakinumab has been shown to be effective in the treatment of systemic juvenile idiopathic arthritis (JIA), but reported adverse events have included macrophage activation syndrome (MAS). This study was undertaken to assess the impact of canakinumab on MAS incidence.MethodsAn independent MAS Adjudication Committee (MASAC), consisting of 3 of the authors, was convened, and a search of databases from clinical studies of canakinumab treatment in systemic JIA was performed using MASAC‐specified adverse event terms to identify potential MAS events. These were then adjudicated as “probable MAS,” “possible MAS,” or “MAS unlikely,” using criteria developed by the MASAC. MAS rates were expressed as numbers of cases per 100 patient‐years.ResultsOf 72 potential MAS cases identified, 21 events (19 with canakinumab treatment; 2 with placebo treatment) in 19 patients were adjudicated as being probable MAS and 10 events in 9 patients as being possible MAS. Systemic JIA was well controlled in the majority of canakinumab‐treated patients at the time of MAS. The time period between initiation of canakinumab treatment and onset of MAS ranged from 3 to 1,358 days (median 292 days). When the rates of probable MAS events were compared between canakinumab‐treated patients (2.8 per 100 patient‐years) and placebo‐treated patients (7.7 per 100 patient‐years), the difference was not significant (−4.9 [95% confidence interval −15.6, 5.9]). There were 3 deaths due to MAS‐related complications (2 in patients receiving canakinumab; 1 in a patient receiving placebo); full recovery was reported in all other patients. Infections were the most common trigger of MAS, and the clinical features of MAS were not modified by canakinumab.ConclusionCanakinumab does not have a significant effect on MAS risk or its clinical features in patients with systemic JIA. Infections are the most common trigger, and MAS occurs even in patients whose systemic JIA is well controlled with this treatment.
Phenotypic, Functional, and Gene Expression Profiling of Peripheral CD45RA+ and CD45RO+ CD4+CD25+CD127low Treg Cells in Patients With Chronic Rheumatoid Arthritis
Authors: Walter Gina J. , Fleskens Veerle , Frederiksen Klaus S. , Rajasekhar Megha , Menon Bina , Gerwien Jens G. , Evans Hayley G. , Taams Leonie S. 
Published: August 2015

ObjectiveConflicting evidence exists regarding the suppressive capacity of Treg cells in the peripheral blood (PB) of patients with rheumatoid arthritis (RA). The aim of this study was to determine whether Treg cells are intrinsically defective in RA.MethodsUsing a range of assays on PB samples from patients with chronic RA and healthy controls, CD3+CD4+CD25+CD127low Treg cells from the CD45RO+ or CD45RA+ T cell compartments were analyzed for phenotype, cytokine expression (ex vivo and after in vitro stimulation), suppression of Teff cell proliferation and cytokine production, suppression of monocyte‐derived cytokine/chemokine production, and gene expression profiles.ResultsNo differences between RA patients and healthy controls were observed with regard to the frequency of Treg cells, ex vivo phenotype (CD4, CD25, CD127, CD39, or CD161), or proinflammatory cytokine profile (interleukin‐17 [IL‐17], interferon‐γ [IFNγ], or tumor necrosis factor [TNF]). FoxP3 expression was slightly increased in Treg cells from RA patients. The ability of Treg cells to suppress the proliferation of T cells or the production of cytokines (IFNγ or TNF) upon coculture with autologous CD45RO+ Teff cells and monocytes was not significantly different between RA patients and healthy controls. In PB samples from some RA patients, CD45RO+ Treg cells showed an impaired ability to suppress the production of certain cytokines/chemokines (IL‐1β, IL‐1 receptor antagonist, IL‐7, CCL3, or CCL4) by autologous lipopolysaccharide‐activated monocytes. However, this was not observed in all patients, and other cytokines/chemokines (TNF, IL‐6, IL‐8, IL‐12, IL‐15, or CCL5) were generally suppressed. Finally, gene expression profiling of CD45RA+ or CD45RO+ Treg cells from the PB revealed no statistically significant differences between RA patients and healthy controls.ConclusionOur findings indicate that there is no global defect in either CD45RO+ or CD45RA+ Treg cells in the PB of patients with chronic RA.
Selective Loss of Signaling Lymphocytic Activation Molecule Family Member 4–Positive CD8+ T Cells Contributes to the Decreased Cytotoxic Cell Activity in Systemic Lupus Erythematosus
Authors: Kis‐Toth Katalin , Comte Denis , Karampetsou Maria P. , Kyttaris Vasileios C. , Kannan Lakshmi , Terhorst Cox , Tsokos George C. 
Published: August 2015

ObjectiveEngagement of signaling lymphocytic activation molecule family member 4 (SLAMF4; CD244, 2B4) by its ligand SLAMF2 (CD48) modulates the function and expansion of both natural killer cells and a subset of cytotoxic CD8+ T cells. Because the cytotoxicity of CD8+ T lymphocytes isolated from patients with systemic lupus erythematosus (SLE) is known to be impaired, the aim of this study was to assess whether the expression and function of the checkpoint regulator SLAMF4 are altered on CD8+ T cells from patients with SLE.MethodsThe expression of SLAMF4 by T cells from healthy donors and patients with SLE was determined by quantitative polymerase chain reaction and flow cytometry. T cells were activated with anti‐CD3 antibody, and degranulation activity was monitored by the surface expression of lysosome‐associated membrane protein 1 (LAMP‐1; CD107a). The SLAMF4+ and SLAMF4− CD8+ T cell subpopulations were characterized by LAMP‐1, perforin, and granzyme B expression and viral peptide–induced proliferation.ResultsSLAMF4 gene and surface protein expression was down‐regulated in CD8+ T cells from SLE patients compared with that in cells obtained from healthy donors. Importantly, SLE patients had significantly fewer SLAMF4+ CD8+ T cells compared with healthy donors. SLAMF4− CD8+ T cells from SLE patients had a decreased cytotoxic capacity and decreased proliferative responses to viral peptides. The loss of memory SLAMF4+ CD8+ T cells in SLE patients was linked to the fact that these cells have an increased propensity to lose CD8 expression and become double‐negative T cells.ConclusionA selective loss of SLAMF4+ CD8+ T cells contributes to the compromised ability of T cells from patients with SLE to fight infection.
Selective Inhibition of Membrane Type 1 Matrix Metalloproteinase Abrogates Progression of Experimental Inflammatory Arthritis: Synergy With Tumor Necrosis Factor Blockade
Authors: Kaneko Kazuyo , Williams Richard O. , Dransfield Daniel T. , Nixon Andrew E. , Sandison Ann , Itoh Yoshifumi 
Published: August 2015

ObjectiveIn rheumatoid arthritis (RA), destruction of articular cartilage by the inflamed synovium is considered to be driven by increased activities of proteolytic enzymes, including matrix metalloproteinases (MMPs). The purpose of this study was to investigate the therapeutic potential of selective inhibition of membrane type 1 MMP (MT1‐MMP) and its combination with tumor necrosis factor (TNF) blockage in mice with collagen‐induced arthritis (CIA).MethodsCIA was induced in DBA/1 mice by immunization with bovine type II collagen. From the onset of clinical arthritis, mice were treated with MT1‐MMP selective inhibitory antibody DX‐2400 and/or TNFR‐Fc fusion protein. Disease progression was monitored daily, and serum, lymph nodes, and affected paws were collected at the end of the study for cytokine and histologic analyses. For in vitro analysis, bone marrow–derived macrophages were stimulated with lipopolysaccharide for 24 hours in the presence of DX‐2400 and/or TNFR‐Fc to analyze cytokine production and phenotype.ResultsDX‐2400 treatment significantly reduced cartilage degradation and disease progression in mice with CIA. Importantly, when combined with TNF blockade, DX‐2400 acted synergistically, inducing long‐term benefit. DX‐2400 also inhibited the up‐regulation of interleukin‐12 (IL‐12)/IL‐23 p40 via polarization toward an M2 phenotype in bone marrow–derived macrophages. Increased production of IL‐17 induced by anti‐TNF, which correlated with an incomplete response to anti‐TNF, was abrogated by combined treatment with DX‐2400 in CIA.ConclusionTargeting MT1‐MMP provides a potential strategy for joint protection, and its combination with TNF blockade may be particularly beneficial in RA patients with an inadequate response to anti‐TNF therapy.