bluuebunny/crossref_metadata_2025 huggingface dataset:
Prolonged Clinical Remission in Patients with Systemic Lupus Erythematosus
Authors: Steiman Amanda J. , Urowitz Murray B. , Ibañez Dominique , Papneja Anjali , Gladman Dafna D.
Published: August 2014

Objective.

Systemic lupus erythematosus (SLE) is typically a relapsing/remitting disease. However, some patients experience prolonged remission. These patients may provide further insights into SLE pathophysiology. In this study we characterize their clinical course.

Methods.

Prolonged remission was defined as Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) = 0, = 2, or = 4 (based on serology) for ≥ 5 consecutive years, with visits ≤ 18 months apart. The patients could be taking antimalarials, but not corticosteroids or immunosuppressives. Flare was defined as clinical activity on SLEDAI-2K, or by corticosteroid/immunosuppressive initiation. Each patient’s preremission course was classified as monophasic, relapsing/remitting, or chronic active. These patients were compared to matched SLE controls and patients achieving remission on medications.

Results.

A total of 38/1613 (2.4%) patients achieved prolonged remission while taking no medications. The mean duration was 11.5 ± 6.4 years. Twenty-seven patients (71.0%) had relapsing/remitting disease, 11 (28.9%) had monophasic illness, and none had chronic active disease prior to remission. They differed from matched controls in ethnicity, disease activity at first visit, and cumulative organ damage. There were 34/1613 patients (2.1%) who achieved prolonged remission while taking steroids and/or immunosuppressives, with mean duration 8.5 ± 2.9 years. Twelve patients (35.3%) experienced disease flare. They were younger at diagnosis, with more disease activity prior to remission than patients taking no medications.

Conclusion.

Prolonged remission is an infrequent outcome among patients and is preceded by an atypically monophasic clinical course in a significant minority. Those taking medications represent a heterogeneous group: those who will tolerate eventual taper, and those whose disease activity was merely suppressed by ongoing immunosuppression. Prolonged remission may reflect unique pathophysiologic mechanisms, and warrants further investigation.
The Role of Depression, Anxiety, Fatigue, and Fibromyalgia on the Evaluation of the Remission Status in Patients with Rheumatoid Arthritis
Authors: Inanc Nevsun , Yilmaz-Oner Sibel , Can Meryem , Sokka Tuulikki , Direskeneli Haner
Published: August 2014

Objective.

To investigate the effect of depression, anxiety, fatigue, and fibromyalgia (FM) on the remission status in patients with rheumatoid arthritis (RA), defined according to the 28-joint count Disease Activity Score (DAS28)-erythrocyte sedimentation rate (ESR) and the Boolean-based new American College of Rheumatology/European League Against Rheumatism remission criteria.

Methods.

The subjects were patients with RA who participated in a hospital-based observational cohort. Patients who met the DAS28-ESR remission criteria at their latest visit were invited to participate in our study. The patient groups fulfilling or not fulfilling the Boolean remission criteria were identified and compared with each other with regard to the presence of depression, anxiety, fatigue (0–50), and FM. The relationship between psychosocial factors and Simplified Disease Activity Index (SDAI) remission, which is the index-based definition of remission in RA, was also investigated.

Results.

A total of 87 out of 428 patients (20%) with RA met the DAS28-ESR remission criteria and 32 (37%) of these also met the Boolean remission criteria, while 55 (63%) did not. Forty patients were also in SDAI remission. In the Boolean remission group, 2 patients had depression and 2 had anxiety (p = 0.004). In the Boolean nonremission group, 19 patients had depression and 13 had anxiety (p = 0.04). Continuous scales of anxiety (3.34 ± 3.76 vs 5.83 ± 4.70, p = 0.012) and depression (2.18 ± 2.75 vs 4.63 ± 4.10, p = 0.001) were also lower in the Boolean remission group in comparison with the nonremission group. Though FM syndrome was detected in only 1 patient of the Boolean remission group and in 7 patients of the Boolean nonremission group (p = 0.249), patients’ polysymptomatic distress scores of FM in the Boolean remission group were significantly lower than those of the nonremission group (3.12 ± 3.25 vs 6.27 ± 5.19, p = 0.001). The mean fatigue scores were 9.5 ± 10.6 in the Boolean remission group and 16.8 ± 12.8 in the Boolean nonremission group (p = 0.006). In multivariate analysis, patient’s global assessment (PtGA) and depression were found as the independent discriminators of Boolean-based definition. Similar relationships were also observed between psychosocial factors and SDAI remission.

Conclusion.

In patients with RA who do not fulfill the Boolean remission criteria, to avoid overtreatment, assessment of anxiety, fatigue, FM, and especially depression must be considered if PtGA scores and disease activity variables are significantly different.
Clinical Characteristics of and Relationship Between Metabolic Components and Renal Function Among Patients with Early-onset Juvenile Tophaceous Gout
Authors: Lu Chuan-Chin , Wu Shyi-Kuen , Chen Han-Yu , Chung Wei-Sheng , Lee Meng-Chih , Yeh Chih-Jung
Published: August 2014

Objective.

Age of onset of gout has recently decreased; however, patients with early-onset gout remain uncommon, and relevant information is scant. We hypothesized that these patients might exhibit differences in serum urates and other comorbidities compared with adult-onset patients.

Methods.

Early-onset gout patients (i.e., juveniles) with (n = 40) and without tophi (n = 47) were enrolled for study. Their clinical characteristics were compared with those of 353 patients with middle-age-onset tophaceous gout and 64 age-matched healthy participants.

Results.

Early-onset gout patients with tophi exhibited significantly higher body mass indices and serum urate levels and lower estimated glomerular filtration rates (eGFR) than did those without tophi. Early-onset gout patients with or without tophi demonstrated significantly abnormal lipid profiles and impaired liver or renal function compared with healthy patients. Serum urate levels and gout duration were identified as the principal determinants of tophi development. The presence of tophi might be crucial in decreasing eGFR, which is inversely related to tophi duration or gout duration. Unexpectedly, the most common site of initial gout attacks in early-onset tophaceous gout patients was the ankle, not the toe, which was the most common site in middle-age-onset tophaceous gout patients. The most common site of first tophi occurrence in early-onset patients was a finger, not a toe, which was the most common site in middle-age-onset patients.

Conclusion.

Early-onset tophaceous gout patients are more likely to exhibit comorbidities and renal dysfunction than middle-age-onset patients and exhibit distinct first sites of gout attack and tophi occurrence patterns.
Adalimumab Significantly Reduces the Recurrence Rate of Anterior Uveitis in Patients with Ankylosing Spondylitis
Authors: van Denderen J. Christiaan , Visman Ingrid M. , Nurmohamed Michael T. , Suttorp-Schulten Maria S.A. , van der Horst-Bruinsma Irene E.
Published: August 2014

Objective.

To investigate whether use of adalimumab decreases the frequency of attacks of anterior uveitis (AU) in patients with ankylosing spondylitis (AS).

Methods.

Consecutive patients with AS, visiting an outpatient clinic and treated for at least 12 weeks with adalimumab, were enrolled. The number of attacks of AU in the year before start and during treatment were assessed by patient history and ophthalmological controls.

Results.

In the 77 patients a total of 52 AU attacks occurred in the year before baseline (68 attacks per 100 patient-yrs), whereas during adalimumab treatment 19 attacks were seen (14 per 100 patient-yrs; reduction rate 80%). Twenty-six patients with AU in the year before start of adalimumab treatment had recurrent attacks, with a median number of 2.0 AU attacks per year [interquartile range (IQR) 1.00–3.00], whereas during treatment this decreased to 10 patients with a median number of 0.56 attacks per year (IQR 0.30–0.75). Hence, the number of attacks per year decreased by 72% (p = 0.000).

Conclusion.

In patients with AS, a significant reduction in the number of AU attacks, as well as in the number of attacks per patient, was observed during adalimumab treatment.
Increased Urinary Interleukin 22 Binding Protein Levels Correlate with Lupus Nephritis Activity
Authors: Yang Xuyan , Gao Yin , Wang Huiying , Zhao Xiaoying , Gong Xubo , Wang Qingqing , Zhang Xiaofei
Published: August 2014

Objective.

Interleukin 22 (IL-22) plays an important role in the promotion of antimicrobial immunity. However, dysregulated IL-22 action leads to inflammation and is involved in autoimmune diseases, including systemic lupus erythematosus (SLE). IL-22 binding protein (IL-22BP) is a soluble inhibitory IL-22 receptor and may represent a crucial regulator of IL-22. We investigated the expression and potential significance of serum and urinary IL-22BP levels in patients with SLE.

Methods.

A total of 112 patients with SLE and healthy control subjects participated in our study. Patients were classified according to kidney involvement and disease activity based on clinical and laboratory measures such as urinary sediment, proteinuria, kidney function, complement factor 3 (C3), C4, anti-dsDNA, disease activity index, and renal SLE disease activity index. The concentrations of IL-22BP and IL-22 were measured by ELISA. The expression of IL-22BP in the renal tissue was detected by immunohistochemistry.

Results.

Patients with active renal disease had urinary levels of IL-22BP higher than (1) patients with active SLE but no renal involvement, (2) patients with a history of lupus nephritis in remission with no systemic disease activity and no history of renal involvement, and (3) control subjects. There was no difference in serum levels of IL-22BP among the groups. Urinary levels of IL-22BP in patients with active renal disease were positively correlated with SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics renal activity score, and histological activity index. IL-22BP was highly expressed in renal tissue of patients with active renal disease. After 6 months of treatment, urinary IL-22BP levels decreased significantly in patients with complete response, but remained unchanged in those with partial or no response.

Conclusion.

Urinary but not serum IL-22BP levels were associated with active renal disease. Urinary levels of IL-22BP might be a potential marker for the presence of renal involvement in patients with SLE.
Alpha-Chlorofatty Acid and Coronary Artery or Aorta Calcium Scores in Women with Systemic Lupus Erythematosus. A Pilot Study
Authors: Mahieu Mary A. , Guild Camelia P. , Albert Carolyn J. , Kondos George T. , Carr James J. , Edmundowicz Daniel , Ford David A. , Ramsey-Goldman Rosalind
Published: August 2014

Objective.

Alpha-chlorofatty acid (α-ClFA) is one product of myeloperoxidase activityin vivoduring atherogenesis and may be a biomarker for cardiovascular disease (CVD). We investigated if serum α-ClFA is associated with subclinical CVD as measured by coronary artery and aorta calcium scores (CAC and AC, respectively) in women with and without systemic lupus erythematosus (SLE).

Methods.

This pilot project analyzed baseline data from 173 women with SLE and 186 women without SLE participating in a 5-year longitudinal investigation of the Study of Lupus Vascular and Bone Long-term Endpoints (SOLVABLE). Data collection included demographic information, CVD and SLE risk factors, and laboratory assessments. Alpha-ClFA was measured in stored serum by liquid chromatography-mass spectrometry. CAC and AC were measured by computed tomography. Outcome measures were CAC and AC present (CAC > 0 or AC > 0) versus absent (CAC = 0 or AC = 0). Associations between risk factors and CAC or AC were tested with descriptive statistics and multivariate analyses.

Results.

Women with SLE had higher α-ClFA levels than women without SLE (42.0 fmol/25µl ± 37.3 vs 34.5 fmol/25µl ± 21.9; p = 0.020). In analyses including individual CVD risk factors, having SLE was independently associated with the presence of CAC (OR 3.42, 95% CI 1.72 to 6.78) but not AC. Alpha-ClFA was not associated with the presence of CAC or AC in patients with SLE.

Conclusion.

SLE, but not serum α-ClFA, was associated with the presence of CAC in this pilot project.
Determinants of Vitamin D Levels in Children, Adolescents, and Young Adults with Juvenile Idiopathic Arthritis
Authors: Stagi Stefano , Bertini Federico , Cavalli Loredana , Matucci-Cerinic Marco , Brandi Maria L. , Falcini Fernanda
Published: August 2014

Objective.

Deficiency of 25-hydroxyvitamin D [25(OH)D] is reported to be common in patients with rheumatoid arthritis (RA); data in patients with juvenile idiopathic arthritis (JIA) are inconsistent. We assessed serum 25(OH)D in children, adolescents and young adults with JIA, in order to identify the risk factors for vitamin D deficiency in patients with JIA.

Methods.

We evaluated 152 patients with JIA: 115 female, 37 male, mean age 16.2 ± 7.4 yrs; evaluated by onset type, 96 had oligoarticular, 35 polyarticular, 7 systemic, and 14 enthesitis-related arthritis (ERA). Patients were compared with a control group matched for sex and age. All patients and controls underwent laboratory tests of plasma 25(OH)D, parathyroid hormone (PTH), calcium, phosphorus, and bone alkaline phosphatase levels, and dual-energy x-ray absorptiometry examination.

Results.

Patients with JIA showed significantly reduced 25(OH)D levels compared to controls (p < 0.001), even divided into subtypes (oligoarticular, p < 0.05; polyarticular, p < 0.005; systemic, p < 0.001; ERA, p < 0.005). Patients with active disease and/or frequent relapses had significantly reduced 25(OH)D levels compared to patients with no active disease and no frequent flares (p < 0.005, respectively). Nevertheless, JIA patients had significantly higher PTH levels compared to controls (p < 0.0001). JIA patients with 25(OH)D deficiency showed a significantly lower bone mineral apparent density than those with normal 25(OH)D levels (p < 0.001).

Conclusion.

JIA patients have reduced 25(OH)D and higher PTH values. This may explain at least in part why JIA patients, despite more effective current drugs, do not achieve bone-normal condition over time. JIA patients with more severe disease could require higher supplementation of vitamin D to maintain normal 25(OH)D serum levels. Longterm studies are needed to investigate the relationship between serum 25(OH)D levels and disease activity in JIA.
Predictors for Mortality in Patients with Antineutrophil Cytoplasmic Autoantibody-associated Vasculitis: A Study of 398 Chinese Patients
Authors: Lai Qing-ying , Ma Tian-Tian , Li Zhi-ying , Chang Dong-yuan , Zhao Ming-Hui , Chen Min
Published: August 2014

Objective.

Patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) have high mortality despite the introduction of immunosuppressive therapy. We investigated factors associated with mortality of patients with AAV in a single Chinese cohort.

Methods.

A total of 398 consecutive patients with AAV diagnosed in our center were recruited. Clinical and laboratory data were collected retrospectively. The predictive values of variables associated with mortality were analyzed.

Results.

During followup of a median duration 25.5 months (range 1–196 mo), 135 out of 398 patients (33.9%) died, with 83 deaths within the first 12 months after diagnosis. Independent predictors of all-cause mortality were age (p < 0.001), secondary infection (p < 0.001), pulmonary involvement of AAV (p = 0.012), and initial renal function (p = 0.001). Secondary infection was the leading cause of death (53/153, 39.3%) during the first year after diagnosis, while cardiovascular event was the leading cause of death (15/53, 28.8%) after 12 months from diagnosis. Independent predictors of secondary infection were age (p = 0.002), initial renal function (p = 0.041), lymphocyte counts in the peripheral blood (p = 0.03), and underlying pulmonary involvement of AAV (p = 0.001).

Conclusion.

Secondary infection is the overall leading cause and independent predictor of death in patients diagnosed with AAV. Cardiovascular event is a major cause of death during the late followup. Prudent monitoring should be given to patients of advancing age with renal dysfunction to reduce adverse events, especially infectious complications.
Tumor Necrosis Factor-α Inhibitor Treatment and the Risk of Incident Cardiovascular Events in Patients with Early Rheumatoid Arthritis: A Nested Case-control Study
Authors: Desai Rishi J. , Rao Jaya K. , Hansen Richard A. , Fang Gang , Maciejewski Matthew , Farley Joel
Published: August 2014

Objective.

To compare the risk of cardiovascular (CV) events between use of tumor necrosis factor-α inhibitors (TNFi) and nonbiologic disease-modifying antirheumatic drugs (DMARD) in patients with early rheumatoid arthritis (RA).

Methods.

A nested case-control study was conducted using data from Truven’s MarketScan commercial and Medicare claims database for patients with early RA who started treatment with either a TNFi or a nonbiologic DMARD between January 1, 2008, and December 31, 2010. Date of CV event diagnosis for cases was defined as the event date, and 12 age-matched and sex-matched controls were sampled using incidence density sampling. Drug exposure was defined into the following mutually exclusive categories hierarchically: (1) current use of TNFi (with or without nonbiologics), (2) past use of TNFi (with or without nonbiologics), (3) current use of nonbiologics only, and (4) past use of nonbiologics only. Current use was defined as any use in the period 90 days prior to the event date. Conditional logistic regression models were used to derive incidence rate ratios (IRR).

Results.

From the cohort of patients with early RA, 279 cases of incident CV events and 3348 matched controls were identified. The adjusted risk of CV events was not significantly different between current TNFi users and current nonbiologic users (IRR 0.92, 95% CI 0.59–1.44). However, past users of nonbiologics showed significantly higher risk compared to current nonbiologic users (IRR 1.47, 95% CI 1.04–2.08).

Conclusion.

No differences in the CV risk were found between current TNFi and current nonbiologic DMARD treatment in patients with early RA.
Clinical and Immunogenetic Factors Associated with Pneumonia in Patients with Systemic Lupus Erythematosus: A Case-Control Study
Authors: Rúa-Figueroa Iñigo , Nóvoa Javier , García-Laorden María Isabel , Erausquin Celia , García-Bello Miguel , Rodríguez de Castro Felipe , Herrera-Ramos Estefanía , Ojeda Soledad , Quevedo Juan Carlos , Francisco Félix , Naranjo Antonio , Rodríguez-Lozano Carlos , Rodríguez-Gallego Carlos
Published: August 2014

Objective.

To determine the incidence of pneumonia and associated factors in a single-center systemic lupus erythematosus (SLE) cohort.

Methods.

We included all our SLE patients [1997 American College of Rheumatology (ACR) criteria] with ≥ 1 pneumonia event, and 196 age and sex-matched SLE controls with no pneumonia events. Cumulative clinical data, weighted Systemic Lupus International Collaborating Clinics/ACR damage index (wSLICC/ACR-DI), comorbidities, and risk factors for pneumonia were retrospectively collected. The standardized incidence ratio (SIR) of pneumonia was estimated. Polymorphisms at genes coding for mannose binding lectin (MBL), MBL-associated serine protease 2, Fc-gamma receptors, and surfactant proteins A1, A2, and D were determined, and their potential association with pneumonia was analyzed. Patients with and without pneumonia were compared using a multivariate logistic regression model for adjustment of pneumonia-associated factors.

Results.

Thirty-six of 232 patients with SLE had experienced ≥ 1 pneumonia event. SIR for pneumonia was 5.1 (95% CI 3.5–7.4; p < 0.0001). Excluding patients receiving immunosuppressive therapy at the time of pneumonia (13%), associations were found for Katz Severity Index (KSI) (p = 0.016), wSLICC/ACR-DI (p = 0.044), number of SLE criteria (p = 0.005), hospital admissions (p < 0.001), FCGR2A HH genotype (p = 0.03), previous use of immunosuppressive therapy (p = 0.049), cutaneous ulcers (p < 0.001), and vasculitis (p = 0.008) in bivariate analyses. In the multivariate analysis adjusted to previous immunosuppressive treatment, only KSI and FCGR2A HH genotype remained statistically significant (p = 0.05 and p = 0.03, respectively).

Conclusion.

The incidence of pneumonia in patients with SLE is higher than that in the general population, and particularly high in severe SLE, regardless of immunosuppressive therapy. The HH genetic variant of FCGR2A appears to predispose patients with SLE to pneumonia.
Bone Structure and Perfusion Quantification of Bone Marrow Edema Pattern in the Wrist of Patients with Rheumatoid Arthritis: A Multimodality Study
Authors: Teruel Jose R. , Burghardt Andrew J. , Rivoire Julien , Srikhum Waraporn , Noworolski Susan M. , Link Thomas M. , Imboden John B. , Li Xiaojuan
Published: August 2014

Objective.

To quantify bone structure and perfusion parameters in regions of bone marrow edema pattern (BMEP), non-edematous bone marrow (NBM), and pannus tissue areas in the wrists of patients with rheumatoid arthritis (RA) using 3-Tesla (3T) magnetic resonance imaging (MRI), and high resolution peripheral quantitative computed tomography (HR-pQCT).

Methods.

Sixteen subjects fulfilling American College of Rheumatology classification were imaged using a HR-pQCT system and a 3T MRI scanner with an 8-channel wrist coil. Coronal T2-weighted and dynamic contrast-enhanced (DCE-MRI) images were acquired. BMEP and pannus tissue areas were segmented semiautomatically in T2-weighted images. NBM areas were placed at a similar distance from the joint space as BMEP regions. MR and HR-pQCT images were registered, and bone variables were calculated within the BMEP and NBM regions. Perfusion parameters in BMEP, pannus tissue, and NBM regions were calculated based on the signal-time curve obtained from DCE-MRI.

Results.

Eighteen BMEP areas were segmented, 15 of them presented proximal to pannus-filled erosions. Significant increases in bone density and trabecular thickness and number were observed in all BMEP regions compared to NMB (p < 0.05). Significantly elevated perfusion measures were observed in both BMEP and pannus tissue regions compared to NBM (p < 0.05).

Conclusion.

BMEP regions showed significantly increased bone density and structures as well as perfusion measures, suggesting bone remodeling and active inflammation. Combining MRI and HR-pQCT provides a powerful multimodality approach for understanding BMEP and erosions, and for potentially identifying novel imaging markers for disease progression in RA.
Patients with Rheumatoid Arthritis Are More Likely to Have Pain and Poor Function After Total Hip Replacements than Patients with Osteoarthritis
Authors: Goodman Susan M. , Ramsden-Stein Danielle N. , Huang Wei-Ti , Zhu Rebecca , Figgie Mark P. , Alexiades Michael M. , Mandl Lisa A.
Published: August 2014

Objective.

Total hip replacement (THR) outcomes have been worse for patients with rheumatoid arthritis (RA) compared with those who have osteoarthritis (OA). Whether this remains true in contemporary patients with RA with a high use of disease-modifying and biologic therapy is unknown. The purpose of our study is to assess pain, function, and quality of life 2 years after primary THR, comparing patients with RA and patients with OA.

Methods.

Baseline and 2-year data were compared between validated patients with RA and patients with OA who were enrolled in a single-center THR registry between May 1, 2007, and February 25, 2011.

Results.

There were 5666 eligible primary THR identified, of which 193 were for RA. RA THR had worse baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (44.8 vs 53.2, p < 0.001) and function (38.7 vs 49.9, p < 0.001) compared with OA. These differences remained after surgery: pain (88.4 vs 94.0, p < 0.001) and function (82.9 vs 91.8, p < 0.001). Patients with RA were as likely to have a significant improvement as patients with OA (Δ WOMAC > 10) in pain (94% vs 96%, p = 0.35) and function (95% vs 94%, p = 0.69), but were 4 times as likely to have worse function (WOMAC ≤ 60; 19% vs 4%, p < 0.001) and pain (12% vs 3%, p < 0.001). In multivariate logistic regression controlling for multiple potential confounders, RA increased the odds of poor postoperative function (OR 4.32, 95% CI 1.57–11.9), and in patients without a previous primary THR, worse postoperative pain (OR 3.17, 95% CI 1.06–9.53).

Conclusion.

Contemporary patients with RA have significant improvements in pain and function after THR, but higher proportions have worse 2-year pain and function. In addition, RA is an independent predictor of 2-year pain and poor function after THR, despite high use of disease-modifying therapy.
Recent Trends in Medication Usage for the Treatment of Juvenile Idiopathic Arthritis and the Influence of Tumor Necrosis Factor Inhibitors
Authors: Mannion Melissa L. , Xie Fenglong , Curtis Jeffrey R. , Beukelman Timothy
Published: August 2014

Objective.

Using administrative data from a large commercial US health insurer, we investigated temporal trends in medication use among children diagnosed with juvenile idiopathic arthritis (JIA).

Methods.

Children with ≥ 1 physician diagnosis code for JIA in the calendar years 2005 through 2012 were included. Use of tumor necrosis factor inhibitors (TNFi), methotrexate (MTX), nonsteroidal antiinflammatory drugs (NSAID), and oral glucocorticoids (GC) was determined. Temporal changes in medication usage were evaluated with the Cochran-Armitage test for trend. We used paired t-tests to evaluate the use of NSAID and GC in the 6 months before and after new TNFi use.

Results.

We identified 4261 unique individuals with JIA. The proportion of patients receiving TNFi increased from 8.7% in 2005 to 22.4% in 2012 (p < 0.0001). MTX use increased from 18.4% to 23.2% (p = 0.02). NSAID use decreased from 49% to 40% (p = 0.02). GC use was relatively unchanged. Following new TNFi use, the mean number of NSAID prescriptions (among prevalent users) decreased from 2.8 to 2.0 (p < 0.0001), and the mean daily GC dose (among prevalent users) decreased from 7.3 mg/day to 3.9 mg/day (p < 0.0001). Many new TNFi users (57%) had not used MTX in the previous 6 months, and only 37% had any concurrent MTX use in the 6 months following new TNFi use.

Conclusion.

TNFi use in the treatment of JIA increased 2- to 3-fold over the last 8 years. New TNFi use was associated with decreased NSAID and GC use. TNFi may be replacing, rather than complementing, MTX in the treatment of many patients.
Fibromyalgia and Physical Trauma: The Concepts We Invent
Authors: Wolfe Frederick , Häuser Winfried , Walitt Brian T. , Katz Robert S. , Rasker Johannes J. , Russell Anthony S.
Published: August 2014

Despite weak to nonexistent evidence regarding the causal association of trauma and fibromyalgia (FM), literature and court testimony continue to point out the association as if it were a strong and true association. The only data that appear unequivocally to support the notion that trauma causes FM are case reports, cases series, and studies that rely on patients’ recall and attribution — very low-quality data that do not constitute scientific evidence. Five research studies have contributed evidence to the FM-trauma association. There is no scientific support for the idea that trauma overall causes FM, and evidence in regard to an effect of motor vehicle accidents on FM is weak or null. In some instances effect may be seen to precede cause. Alternative causal models that propose that trauma causes “stress” that leads to FM are unfalsifiable and unmeasurable.
Immune Subdominant Antigens as Vaccine Candidates against Mycobacterium tuberculosis
Authors: Orr Mark T. , Ireton Gregory C. , Beebe Elyse A. , Huang Po-Wei D. , Reese Valerie A. , Argilla David , Coler Rhea N. , Reed Steven G.
Published: August 2014

Unlike most pathogens, many of the immunodominant epitopes from Mycobacterium tuberculosis are under purifying selection. This startling finding suggests that M. tuberculosis may gain an evolutionary advantage by focusing the human immune response against selected proteins. Although the implications of this to vaccine development are incompletely understood, it has been suggested that inducing strong Th1 responses against Ags that are only weakly recognized during natural infection may circumvent this evasion strategy and increase vaccine efficacy. To test the hypothesis that subdominant and/or weak M. tuberculosis Ags are viable vaccine candidates and to avoid complications because of differential immunodominance hierarchies in humans and experimental animals, we defined the immunodominance hierarchy of 84 recombinant M. tuberculosis proteins in experimentally infected mice. We then combined a subset of these dominant or subdominant Ags with a Th1 augmenting adjuvant, glucopyranosyl lipid adjuvant in stable emulsion, to assess their immunogenicity in M. tuberculosis–naive animals and protective efficacy as measured by a reduction in lung M. tuberculosis burden of infected animals after prophylactic vaccination. We observed little correlation between immunodominance during primary M. tuberculosis infection and vaccine efficacy, confirming the hypothesis that subdominant and weakly antigenic M. tuberculosis proteins are viable vaccine candidates. Finally, we developed two fusion proteins based on strongly protective subdominant fusion proteins. When paired with the glucopyranosyl lipid adjuvant in stable emulsion, these fusion proteins elicited robust Th1 responses and limited pulmonary M. tuberculosis for at least 6 wk postinfection with a single immunization. These findings expand the potential pool of M. tuberculosis proteins that can be considered as vaccine Ag candidates.
Sperm-Associated Antigen 16 Is a Novel Target of the Humoral Autoimmune Response in Multiple Sclerosis
Authors: de Bock Laura , Somers Klaartje , Fraussen Judith , Hendriks Jerome J.A. , van Horssen Jack , Rouwette Myrthe , Hellings Niels , Villar Luisa M. , Álvarez-Cermeño José C. , Espiño Mercedes , Hupperts Raymond , Jongen Peter , Damoiseaux Jan , Verbeek Marcel M. , De Deyn Peter P. , D’hooghe Marie , Van Wijmeersch Bart , Stinissen Piet , Somers Veerle
Published: August 2014

We have previously identified eight novel autoantibody targets in the cerebrospinal fluid of multiple sclerosis (MS) patients, including sperm-associated Ag 16 (SPAG16). In the current study, we further investigated the autoantibody response against SPAG16—a protein with unknown function in the CNS—and its expression in MS pathology. Using isoelectric focusing, we detected SPAG16-specific oligoclonal bands in the cerebrospinal fluid of 5 of 23 MS patients (22%). Analysis of the anti-SPAG16 Ab reactivity in the plasma of a total of 531 donors using ELISA demonstrated significantly elevated anti-SPAG16 Ab levels (p = 0.002) in 32 of 153 MS patients (21%) compared with all other control groups with 95% specificity for the disease. To investigate the pathologic relevance of anti-SPAG16 Abs in vivo, anti-SPAG16 Abs were injected in mice with experimental autoimmune encephalomyelitis, resulting in a significant disease exacerbation. Finally, we demonstrated a consistent upregulation of SPAG16 in MS brain and experimental autoimmune encephalomyelitis spinal cord lesions, more specifically in reactive astrocytes. We conclude that SPAG16 is a novel autoantibody target in a subgroup of MS patients and in combination with other diagnostic criteria, elevated levels of anti-SPAG16 Abs could be used as a biomarker for diagnosis. Furthermore, the pathologic relevance of anti-SPAG16 Abs was shown in vivo.
Th17 Cells Demonstrate Stable Cytokine Production in a Proallergic Environment
Authors: Glosson-Byers Nicole L. , Sehra Sarita , Stritesky Gretta L. , Yu Qing , Awe Olufolakemi , Pham Duy , Bruns Heather A. , Kaplan Mark H.
Published: August 2014

Th17 cells are critical for the clearance of extracellular bacteria and fungi, but also contribute to the pathology of autoimmune diseases and allergic inflammation. After exposure to an appropriate cytokine environment, Th17 cells can acquire a Th1-like phenotype, but less is known about their ability to adopt Th2 and Th9 effector programs. To explore this in more detail, we used an IL-17F lineage tracer mouse strain that allows tracking of cells that formerly expressed IL-17F. In vitro–derived Th17 cells adopted signature cytokine and transcription factor expression when cultured under Th1-, Th2-, or Th9-polarizing conditions. In contrast, using two models of allergic airway disease, Th17 cells from the lungs of diseased mice did not adopt Th1, Th2, or Th9 effector programs, but remained stable IL-17 secretors. Although in vitro–derived Th17 cells expressed IL-4Rα, those induced in vivo during allergic airway disease did not, possibly rendering them unresponsive to IL-4–induced signals. However, in vitro–derived, Ag-specific Th17 cells transferred in vivo to OVA and aluminum hydroxide–sensitized mice also maintained IL-17 secretion and did not produce alternative cytokines upon subsequent OVA challenge. Thus, although Th17 cells can adopt new phenotypes in response to some inflammatory environments, our data suggest that in allergic inflammation, Th17 cells are comparatively stable and retain the potential to produce IL-17. This might reflect a cytokine environment that promotes Th17 stability, and allow a broader immune response at tissue barriers that are susceptible to allergic inflammation.
Increasing biomass carbon stocks in trees outside forests in China over the last three decades
Authors: Guo Z. D. , Hu H. F. , Pan Y. D. , Birdsey R. A. , Fang J. Y.
Published: August 2014

Abstract. Trees outside forests (TOF) play important roles in national economies, ecosystem services, and international efforts for mitigating climate warming. Detailed assessment of the dynamics of carbon (C) stocks in China's TOF is necessary for fully evaluating the role of the country's trees in the national C cycle. This study is the first to explore the changes in biomass C stocks of China's TOF over the last three decades, using the national forest inventory data in six periods from 1977 to 2008. According to the definition of the forest inventory, China's TOF could be categorized into three groups: woodlands, shrubberies, and trees on non-forest land (including four-side greening trees, defined in the article, and scattered trees). We estimated biomass C stocks of woodlands and trees on non-forest land by using the provincial biomass-volume conversion equations derived from the data of low-canopy forests, and estimated the biomass C stocks of shrubberies using the provincial mean biomass density. Total TOF biomass C stock increased by 62.7% from 823 Tg C (1 Tg = 1012 g) in the initial period of 1977–1981 to 1339 Tg C in the last period of 2004–2008. As a result, China's TOF have accumulated biomass C of 516 Tg during the study period, with 12, 270, and 234 Tg in woodlands, shrubberies, and trees on non-forest land, respectively. The annual biomass C sink of China's TOF averaged 19.1 Tg C yr−1, offsetting 2.1% of the contemporary fossil-fuel CO2 emissions in the country. These estimates are equal to 16.5–20.7% of the contemporary total forest biomass C stock and 27.2% of the total forest biomass C sink in the country, suggesting that TOF are substantial components in China's tree C budget.
Benchmarking hydrological models for low-flow simulation and forecasting on French catchments
Authors: Nicolle P. , Pushpalatha R. , Perrin C. , François D. , Thiéry D. , Mathevet T. , Le Lay M. , Besson F. , Soubeyroux J.-M. , Viel C. , Regimbeau F. , Andréassian V. , Maugis P. , Augeard B. , Morice E.
Published: August 2014

Abstract. Low-flow simulation and forecasting remains a difficult issue for hydrological modellers, and intercomparisons can be extremely instructive for assessing existing low-flow prediction models and for developing more efficient operational tools. This research presents the results of a collaborative experiment conducted to compare low-flow simulation and forecasting models on 21 unregulated catchments in France. Five hydrological models (four lumped storage-type models – Gardenia, GR6J, Mordor and Presages – and one distributed physically oriented model – SIM) were applied within a common evaluation framework and assessed using a common set of criteria. Two simple benchmarks describing the average streamflow variability were used to set minimum levels of acceptability for model performance in simulation and forecasting modes. Results showed that, in simulation as well as in forecasting modes, all hydrological models performed almost systematically better than the benchmarks. Although no single model outperformed all the others for all catchments and criteria, a few models appeared to be more satisfactory than the others on average. In simulation mode, all attempts to relate model efficiency to catchment or streamflow characteristics remained inconclusive. In forecasting mode, we defined maximum useful forecasting lead times beyond which the model does not bring useful information compared to the benchmark. This maximum useful lead time logically varies between catchments, but also depends on the model used. Simple multi-model approaches that combine the outputs of the five hydrological models were tested to improve simulation and forecasting efficiency. We found that the multi-model approach was more robust and could provide better performance than individual models on average.
A century of sea level data and the UK's 2013/14 storm surges: an assessment of extremes and clustering using the Newlyn tide gauge record
Authors: Wadey M. P. , Haigh I. D. , Brown J. M.
Published: August 2014

Abstract. For the UK's longest and most complete sea level record (Newlyn), we assess extreme high water events and their temporal clustering; prompted by the 2013/2014 winter of flooding and storms. These are set into context against this almost 100 yr record. We define annual periods for which storm activity, tides and sea levels can be compared on a year-by-year basis. Amongst the storms and high tides which affected Newlyn the recent winter produced the largest recorded high water (3 February 2014) and five others above a 1 in 1 yr return period. The large magnitude of tide and mean sea level, and the close inter-event spacings (of large return period high waters), suggests that the 2013/2014 high water "season" may be considered the most extreme on record. However, storm and sea level events may be classified in different ways. For example in the context of sea level rise (which we calculate linearly as 1.81 ± 0.1 mm yr−1 from 1915 to 2014), a lower probability combination of surge and tide occurred on 29 January 1948, whilst 1995/1996 storm surge season saw the most high waters of ≥ 1 in 1 yr return period. We provide a basic categorisation of five types of high water cluster, ranging from consecutive tidal cycles to multiple years. The assessment is extended to other UK sites (with shorter sea level records and different tide-surge characteristics), which suggests 2013/2014 was extreme, although further work should assess clustering mechanisms and flood system "memory".
The influence of edge effects on crack propagation in snow stability tests
Authors: Bair E. H. , Simenhois R. , van Herwijnen A. , Birkeland K.
Published: August 2014

Abstract. The Extended Column Test (ECT) and the Propagation Saw Test (PST) are two commonly used tests to assess the likelihood of crack propagation in a snowpack. Guidelines suggest beams with lengths of around 1 m, yet little is known about how test length affects propagation. Thus, we performed 163 ECTs and PSTs 1.0–10.0 m long. On days with full crack propagation in 1.0–1.5 m tests, we then made videos of tests 2.0–10.0 m long. We inserted markers for particle tracking to measure collapse amplitude, propagation speed, and wavelength. We also used a finite element (FE) model to simulate the strain energy release rate at fixed crack lengths. We find that (1) the proportion of tests with full propagation decreased with test length; (2) collapse was greater at the ends of the beams than in the centers; (3) collapse amplitude was independent of beam length and did not reach a constant value; (4) collapse wavelengths in the longer tests were around 3 m, two times greater than what is predicted by the anticrack model. We also confirmed the prediction that centered PSTs had double the critical length of edge PSTs. Based on our results, we conclude that cracks propagated more frequently in the shorter tests because of increased stress concentration from the far edge. The FE model suggests this edge effect occurs for PSTs of up to 2 m long or a crack to beam length ratio ≥ 0.20. Our results suggest that ECT and PST length guidelines may need to be revisited.
Environmental Factors and Puberty Onset: An Update
Authors: Nabi Ghulam , Amin Muhammad , Sultan Rishma , Kamil Muhammad
Published: August 2014

Puberty is a process that results from a coordinated series of complex neuroendocrine changes which eventually leads to external and internal physical changes. These changes include attainment of primary and secondary sexual characteristics. Puberty as a temporal process is subdivided into different stages. These pubertal stages occur in a sequential manner but significant variations have been seen among different individuals in the timings of pubertal onset as well as a certain degree of gender difference is also present where puberty is occurring earlier in girls than boys. Among many aetiologies which have been hypothesized to be involved, environmental cues are the most ones. This review article describes the recent findings of the influences of the key environmental clues on pubertal timings, emphasizing on the aspects for which the most scientific evidences exist.
Research Note: Exaggeration Bias-Corrected Contingent Valuation Method: The Case of Olle Trail
Authors: Lee Won Seok , Lee Choong-Ki , Yoon Yooshik , Kim Jihee
Published: August 2014

Researchers have criticized the traditional contingent valuation method (CVM) due to its potential response bias. To address this bias, several studies have employed improved CVM survey designs. When respondents disguise the truth, non-sampling errors are created that cannot be corrected by these elaborate survey modifications. To reduce this type of non-sampling error, Park and MacLachlan (2008) suggested the exaggeration bias-corrected (EBC) CVM, which assumes a functional mechanism between real and spurious willingness to pay (WTP). The authors verify the effectiveness of the EBC-CVM in non-sampling error reduction, which in turn derives more error-corrected economic value. Few studies have employed the EBC-CVM in a tourism context. The main goals of this study are to introduce EBC-CVM and to test its validity in a tourism study. The results indicate that EBC-CVM contributes to the reduction of non-sampling errors. The implications of the findings are discussed.
Is Participation in the Tourism Market an Opportunity for Everyone? Some Evidence from Italy
Authors: Bernini Cristina , Cracolici Maria Francesca
Published: August 2014

This paper investigates whether there are differences in tourism consumption behaviour among families by analysing the main determinants of tourism participation at national and international levels. In particular, it explores whether tourism is becoming part of the lifestyle of Italians or whether it is still a luxury good only for the privileged. A Heckman model was used on micro-data on Italian family expenditure over the period 1997–2007, and an income elasticity analysis for different personal and household characteristics was carried out. The results show that participation in the tourism market is strongly affected by the personal characteristics of individuals and that tourism consumption is an income-sensitive good. The analysis reveals that tourism is generally a luxury good. Income elasticity analysis shows both similarities as well as differences in Italian tourism consumption patterns at national and international levels. The authors find that consumption behaviour in tourism is affected not only by economic constraints but also by cultural and territorial factors.
Assessing the potential of solar energy in pressurized irrigation networks. The case of Bembézar MI irrigation district (Spain)
Authors: Carrillo-Cobo M. Teresa , Camacho-Poyato Emilio , Montesinos Pilar , Rodríguez Díaz Juan A.
Published: August 2014

The high energy requirements and the rising costs highlight the need to reduce the energy dependence of the irrigation sector. Alternative management strategies have been developed to reduce the energy consumption of the irrigated areas and to improve the efficiency in the water and energy use. In addition, the renewable energy sources are starting to be considered as an alternative to reduce energy costs with smaller environmental impacts. In this work, a new methodology, that combines sectoring as energy saving measure and solar energy, is developed. Thus, it reduces the energy requirements and the dependence on conventional energy resources. This methodology is applied to the irrigation district of Bembézar Margen Izquierda (Córdoba, Spain). The results show that organizing the network in two irrigation sectors, annual potential energy savings of 30.8% were achieved. Therefore, this measure reduces the annual energy bill in 30.4% without major investments. Then, a 2.1 MW photovoltaic would supply energy to the sector with higher energy consumption. However, conventional energy would be required (with an annual cost of € 33.6 ha-1) when solar energy is not available or it is not enough to supply the demanded flows. Both measures together would reduce the energy costs in 71.7% and the greenhouse gases emissions in 70.5%. The total investment would be M€ 2.8 but with a payback period of 8 years. At present, solar energy is a technically and economically viable alternative, which offers both economic and environmental benefits.
El poder de las redes sociales: la “mano invisible” del framing noticioso. El caso de #LadyProfeco.
Authors: Nabel Luis Cesar Torres
Published: August 2014

El artículo discute,  a partir del caso sobre #LadyProfeco en México, la hipótesis de la influencia de enmarcamiento (framing) que están ejerciendo las redes sociales sobre los temas públicos importantes. Los resultados del análisis sobre el caso dan evidencia en contra de esta hipótesis ya que pese al crecimiento de las redes sociales y su visibilidad en la agenda pública, el 66.3% de la opinión que se vierte en hashtags y trending topics es producida por los  de periodistas, militantes partidistas y políticos profesionales que la establecían desde los medios tradicionales.
Biases of April 1 snow water equivalent records in the Sierra Nevada and their associations with large‐scale climate indices
Authors: Montoya E. L. , Dozier J. , Meiring W.
Published: August 2014

Do the April 1 snow course measurements underestimate the snow accumulation peak in the Sierra Nevada, thus possibly introducing biases in studies of trends and interannual variability that use the April 1 data? Although their period of record is many decades shorter, measurements of snow water equivalent (SWE) from automated snow pillows provide daily records throughout each year, enabling us to examine the timing and magnitude of the maximum SWE accumulation. Using generalized additive mixed models, on average, we find that the peak occurs earlier than April 1 at the lowest elevations and later than April 1 at the highest elevations and that the degree to which April 1 SWE under‐measures maximum SWE is greatest at the lowest and highest elevations. In addition, our results show that the biases are associated with cold and warm phase interactions of certain climate indices.