bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-stakeholder decision-making in the risk-based design of a RO-PAX double bottom for grounding
Authors: Klanac A , Jalonen R , Varsta P
Published: February 2007

Grounding accidents can be fatal for ships. This paper discusses decision-making in risk-based design to avoid such outcomes for a 30 000 GT RO-PAX in a powered hard grounding. Five alternatives of a double-bottom structure are suggested to reduce the risks of loss of life, environmental damage, and material damage. Risk assessment concentrates on the consequences, applying numerical grounding simulations to model the energy absorption of the proposed alternatives. To determine the risks, 1295 Monte Carlo simulations are performed running a quasi-static model of ship motions. Accounting for these risks and the added production costs and operational loss, a new multi-stakeholder approach for selecting alternatives is proposed assuring simultaneous maximal satisfaction to both the shipyard and the ship owner. As an outcome, two alternatives are selected, the first increasing the bottom shell thickness by 50 per cent, and the second increasing the stiffness of longitudinal stiffeners by 90 per cent. If observing their performance, it is possible to recommend the latter as the most effective solution. Such an outcome is in accordance with the established practical opinions in increasing safety for grounding, proving sagacity of the presented approach.
A Min-Max Relation on Packing Feedback Vertex Sets
Authors: Chen Xujin , Ding Guoli , Hu Xiaodong , Zang Wenan
Published: February 2007

Let G be a graph with a nonnegative integral function w defined on V(G). A collection ℱ of subsets of V(G) (repetition is allowed) is called a feedback vertex set packing in G if the removal of any member of ℱ from G leaves a forest, and every vertex v ∈ V(G) is contained in at most w(v) members of ℱ. The weight of a cycle C in G is the sum of w(v), over all vertices v of C. The purpose of this paper is to characterize all graphs with the property that, for any nonnegative integral function w, the maximum cardinality of a feedback vertex set packing is equal to the minimum weight of a cycle.
A Limit Theorem for Financial Markets with Inert Investors
Authors: Bayraktar Erhan , Horst Ulrich , Sircar Ronnie
Published: February 2007

We study the effect of investor inertia on stock price fluctuations with a market microstructure model comprising many small investors who are inactive most of the time. It turns out that semi-Markov processes are tailor made for modelling inert investors. With a suitable scaling, we show that when the price is driven by the market imbalance, the log price process is approximated by a process with long-range dependence and non-Gaussian returns distributions, driven by a fractional Brownian motion. Consequently, investor inertia may lead to arbitrage opportunities for sophisticated market participants. The mathematical contributions are a functional central limit theorem for stationary semi-Markov processes and approximation results for stochastic integrals of continuous semimartingales with respect to fractional Brownian motion.
Polynomial-Time Separation of a Superclass of Simple Comb Inequalities
Authors: Fleischer Lisa K. , Letchford Adam N. , Lodi Andrea
Published: February 2007

The comb inequalities are a well-known class of facet-inducing inequalities for the traveling salesman problem, defined in terms of certain vertex sets called the handle and the teeth. We say that a comb inequality is simple if the following holds for each tooth: Either the intersection of the tooth with the handle has cardinality one, or the part of the tooth outside the handle has cardinality one, or both. The simple comb inequalities generalize the classical 2-matching inequalities of Edmonds [Edmonds, J. 1965. Maximum matching and a polyhedron with 0–1 vertices. J. Res. Nat. Bur. Standards 69B 125–130] and also the so-called Chvátal comb inequalities. In 1982, Padberg and Rao [Padberg, M. W., M. R. Rao. 1982. Odd minimum cut-sets and b-matchings. Math. Oper. Res. 7 67–80] gave a polynomial-time separation algorithm for the 2-matching inequalities, i.e., an algorithm for testing if a given fractional solution to an LP relaxation violates a 2-matching inequality. We extend this significantly by giving a polynomial-time separation algorithm for a class of valid inequalities which includes all simple comb inequalities.
Solving Stochastic Mathematical Programs with Complementarity Constraints Using Simulation
Authors: Birbil Ş. İlker , Gürkan Gül , Listeş Ovidiu
Published: February 2007

We consider stochastic mathematical programs with complementarity constraints in which both the objective and constraints involve limit functions that need to be approximated. Such programs can be used for modeling “average” (expected) or steady-state behavior of complex stochastic systems. We first describe these stochastic mathematical programs with complementarity constraints and compare them with different stochastic mathematical programs with equilibrium constraints from the literature. This explicit discussion may facilitate selecting an appropriate stochastic model. We then describe a simulation-based method called sample-path optimization for solving these problems and provide sufficient conditions under which appropriate approximating problems will have solutions converging to a solution of the original problem almost surely. We illustrate an application on toll pricing in transportation networks. We explain how uncertainty can be incorporated and the approximating problems are solved using an off-the-shelf solver. These developments enable solving certain stochastic bilevel optimization problems and Stackelberg games using simulation.
Auction Algorithms for Market Equilibrium
Authors: Garg Rahul , Kapoor Sanjiv
Published: February 2007

In this paper we study algorithms for computing market equilibrium in markets with linear utility functions. The buyers in the market have an initial endowment given by a portfolio of goods. The market equilibrium problem is to compute a price vector that ensures market clearing, i.e., the demand of a positively priced good equals its supply, and given the prices, each buyer maximizes its utility. The problem is of considerable interest in economics. This paper presents a formulation of the market equilibrium problem as a parameterized linear program. We construct a family of duals corrresponding to these parameterized linear programs and show that finding the market equilibrium is the same as finding a linear program from this family of linear programs. The market-clearing conditions arise naturally from complementary slackness conditions. We then define an auction mechanism that computes prices such that approximate market clearing is achieved. The algorithm we obtain outperforms previously known methods.
An Efficient Interior-Point Method for Convex Multicriteria Optimization Problems
Authors: Fliege Jörg
Published: February 2007

In multicriteria optimization, several objective functions have to be minimized simultaneously. We propose a new efficient method for approximating the solution set of a multicriteria optimization problem, where the objective functions involved are arbitrary convex functions and the set of feasible points is convex. The method is based on generating warm-start points for an efficient interior-point algorithm, while the approximation computed consists of a finite set of discrete points. Polynomial-time complexity results for the method proposed are derived. In these estimates, the number of operations per point decreases when the number of points generated for the approximation increases. This reduced theoretical complexity estimate is a novel feature and is not observed in standard solution techniques for multicriteria optimization problems.
Compound Poisson Disorder Problem
Authors: Dayanik Savas , Sezer Semih Onur
Published: February 2007

In the compound Poisson disorder problem, arrival rate and/or jump distribution of some compound Poisson process changes suddenly at some unknown and unobservable time. The problem is to detect the change (or disorder) time as quickly as possible. A sudden regime shift may require some countermeasures be taken promptly, and a quickest detection rule can help with those efforts. We describe complete solution of the compound Poisson disorder problem with several standard Bayesian risk measures. Solution methods are feasible for numerical implementation and are illustrated by examples.
Evaluation of Assigned-Value Uncertainty for Complex Calibrator Value Assignment Processes: A Prealbumin Example
Authors: Middleton John , Vaks Jeffrey E
Published: February 2007

Background: Errors of calibrator-assigned values lead to errors in the testing of patient samples. The ability to estimate the uncertainties of calibrator-assigned values and other variables minimizes errors in testing processes. International Organization of Standardization guidelines provide simple equations for the estimation of calibrator uncertainty with simple value-assignment processes, but other methods are needed to estimate uncertainty in complex processes.

Methods: We estimated the assigned-value uncertainty with a Monte Carlo computer simulation of a complex value-assignment process, based on a formalized description of the process, with measurement parameters estimated experimentally. This method was applied to study uncertainty of a multilevel calibrator value assignment for a prealbumin immunoassay.

Results: The simulation results showed that the component of the uncertainty added by the process of value transfer from the reference material CRM470 to the calibrator is smaller than that of the reference material itself (<0.8% vs 3.7%). Varying the process parameters in the simulation model allowed for optimizing the process, while keeping the added uncertainty small. The patient result uncertainty caused by the calibrator uncertainty was also found to be small.

Conclusions: This method of estimating uncertainty is a powerful tool that allows for estimation of calibrator uncertainty for optimization of various value assignment processes, with a reduced number of measurements and reagent costs, while satisfying the requirements to uncertainty. The new method expands and augments existing methods to allow estimation of uncertainty in complex processes.
Systematic review of clinical trials of treatments for osteoarthritis in dogs
Authors: Aragon Carlos L. , Hofmeister Erik H. , Budsberg Steven C.
Published: February 2007

Objective—To identify and critically evaluate the quality of evidence of the most commonly used pharmacologic, nutraceutical, and purported slow-acting drugs of osteoarthritis for the management of osteoarthritis in dogs by use of the FDA's evidence-based medicine scoring system.

Design—Systematic review.

Sample Population—16 clinical trials.

Procedures—A broad bibliographic search was performed prior to May 2006. Inclusion criteria focused on prospective trials evaluating commonly used medical treatment interventions for the management of osteoarthritis in dogs and published in peer-reviewed journals. The analysis consisted of the following: study design rating, quality factor rating, quantity rating, consistency rating, relevance to disease risk reduction rating, and cumulative strength of evidence ranking.

Results—4 trials evaluating meloxicam were rated as type I.Three trials evaluating carprofen were rated as type I, and 2 trials were rated as type III. One trial evaluating each of the following agents was rated as type 1: etodolac; P54FP; polysulfated glycosaminoglycan; and a combination of chondroitin sulfate, glucosamine hydrochloride, and manganese ascorbate. Two trials evaluating pentosan polysulphate and 2 trails evaluating green-lipped mussels were rated as type I. One trial evaluating hyaluronan was rated as type III.

Conclusions and Clinical Relevance—A high level of comfort exists for meloxicam that the claimed relationship is scientifically valid and that its use is clinically efficacious for the treatment of osteoarthritis in dogs.A moderate level of comfort exists for carprofen; etodolac; pentosan polysulphate; green-lipped mussels; P54FP; polysulfated glycosaminoglycans; and a combination of chondroitin sulfate, glucosamine hydrochloride, and manganese ascorbate. An extremely low level of comfort exists for hyaluronan.
Serum C-reactive protein concentrations in dogs with multicentric lymphoma undergoing chemotherapy
Authors: Merlo Alexandre , Rezende Bárbara Cristina Gagliano , Franchini Maria Luisa , Simões Denise Maria Nunes , Lucas Sílvia Regina Ricci
Published: February 2007

Objective—To determine whether serum C-reactive protein (CRP) concentration is high in dogs with multicentric lymphoma, whether CRP concentration changes in response to chemotherapy, and whether CRP concentration can be used as a marker for relapse in dogs with multicentric lymphoma.

Design—Cohort study.

Animals—20 dogs with multicentric lymphoma and 8 healthy control dogs undergoing chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP) or with vincristine, cyclophosphamide, methotrexate, and L-asparaginase (VCMA) and 20 other healthy dogs.

Procedures—Serum CRP concentration was measured weekly during the first month of chemotherapy and then at 3-week intervals until relapse in dogs with multicentric lymphoma, weekly for 16 weeks in healthy dogs undergoing chemotherapy, and once in the healthy dogs not undergoing chemotherapy.

Results—For both groups of dogs with lymphoma, mean serum CRP concentration during week 1 (prior to treatment) was significantly higher than mean concentrations following induction of chemotherapy and at the time of relapse.Mean serum CRP concentration in the healthy dogs undergoing chemotherapy was not significantly different at any time from mean concentration for the healthy dogs not undergoing chemotherapy.No significant dif ferences were observed between dogs treated with CVP and dogs treated with VCMA.

Conclusions and Clinical Relevance—Results suggest that serum CRP concentration is high in dogs with multicentric lymphoma but that serum CRP concentration is not a useful marker for relapse and that chemotherapy itself does not affect serum CRP concentration.
Use of vascular access ports with intrathoracic drains for treatment of pleural effusion in three dogs
Authors: Cahalane Alane K. , Flanders James A. , Steffey Michele A. , Rassnick Kenneth M.
Published: February 2007

Case Description—3 dogs (9 to 12 years old) were evaluated because of recurrent pleural effusion that was refractory to treatment of the underlying cause.

Clinical Findings—Dogs were evaluated because of cough, dyspnea, tachypnea, or lethargy or a combination of these clinical signs. Radiography, ultrasonography, or thoracocentesis were used to confirm the presence of pleural fluid in each dog. A neoplastic cause of pleural effusion was confirmed in 2 dogs. In 1 dog, fasciitis of the mediastinum and the left parietal pleura was diagnosed, with no evidence of neoplasia.

Treatment and Outcome—Each dog was anesthestized, and thoracotomy was performed with manual perforation of the mediastinum. Permanent, subcutaneously placed vascular access ports were attached to intrathoracic, Jackson-Pratt drain tubing for repeated drainage of pleural fluid. Drains were used successfully in the 3 dogs for periods of 6 weeks, 11 weeks, and > 3 years.

Clinical Relevance—Findings suggest that subcutaneous vascular access ports attached to intrathoracic drain tubing may be an effective way to remove recurrent pleural effusion in dogs.
Systemic infection with Geomyces organisms in a dog with lytic bone lesions
Authors: Erne Jay B. , Walker Mark C. , Strik Nicole , Alleman A. Rick
Published: February 2007

Case Description—A 5-year-old neutered male mixed-breed dog was evaluated by a veterinarian because of a 4-week history of progressive lethargy and poor appetite; the dog was then examined at a referral hospital.

Clinical Findings—Hyperglobulinemia was identified via serum biochemical analyses performed before and after arrival at the hospital. Lysis of sternebrae 1 and 2 and sternal lymphadenopathy were detected radiographically. Fine-needle aspirates were collected from the affected sternebrae and lymph node for cytologic examination; findings were consistent with pyogranulomatous inflammation associated with fungal infiltrates. Geomyces organisms were identified via microbial culture of sternebral aspirates.

Treatment and Outcome—Treatment consisted of oral administration of itraconazole. After 6 months, remodeling of the affected sternebrae and resolution of sternebral lysis were evident radiographically. Geomyces organisms and pyogranulomatous infiltrates persisted despite clinical improvement. Treatment with itraconazole was continued for an additional 3 months.

Clinical Relevance—Infection with Geomyces organisms is typically localized to the skin and nail beds. In the dog of this report, systemic dissemination of Geomyces organisms resulted in lysis of the first 2 sternebrae. Cytologic examination of fine-needle aspirates and microbial culture of samples of the affected sternebrae were important diagnostic tests for successful identification of the organism. Despite 6 months of itraconazole administration and evidence of clinical improvement, fungal organisms persisted in the dog's affected sternebrae. Practitioners should include Geomyces infection among the differential diagnoses for suspected systemic mycosis and should perform cytologic examination and microbial culture of affected tissue throughout treatment of affected dogs.
Use of successive dynamic videoendoscopic evaluations to identify progression of recurrent laryngeal neuropathy in three horses
Authors: Davidson Elizabeth J. , Martin Benson B. , Parente Eric J.
Published: February 2007

Case Description—3 racehorses were evaluated because of poor performance or abnormal noise originating from the upper portion of the respiratory tract.

Clinical Findings—During maximal exercise, initial dynamic videoendoscopy of the upper respiratory tract revealed complete arytenoid cartilage abduction in 2 horses and incomplete but adequate abduction of the left arytenoid cartilage in 1 horse. Subsequent exercising endoscopic evaluation revealed severe dynamic collapse of the left arytenoid cartilage and vocal fold in all 3 horses.

Treatment and Outcome—2 horses were treated with prosthetic left laryngoplasty and raced successfully. One horse was retired from racing.

Clinical Relevance—Idiopathic laryngeal hemiplegia can be a progressive disease. Successive dynamic videoendoscopic upper airway evaluations were used to confirm progression of left laryngeal hemiplegia in these 3 horses. Videoendoscopy of the upper respiratory tract during exercise should be considered as part of the clinical evaluation of horses with signs of upper respiratory tract dysfunction.
Aggression, conflict resolution, popularity, and attitude to school in Russian adolescents
Authors: Butovskaya Marina L. , Timentschik Vera M. , Burkova Valentina N.
Published: February 2007

The objective of the present study was to examine the effects of aggression and conflict‐managing skills on popularity and attitude to school in Russian adolescents. Three types of aggression (physical, verbal, and indirect), constructive conflict resolution, third‐party intervention, withdrawal, and victimization were examined using the Peer‐Estimated Conflict Behavior (PECOBE) inventory [Bjorkquist and Osterman, 1998]. Also, all respondents rated peer and self‐popularity with same‐sex classmates and personal attitude to school. The sample consisted of 212 Russian adolescents (101 boys, 111 girls) aged between 11 and 15 years. The findings attest to significant sex differences in aggression and conflict resolution patterns. Boys scored higher on physical and verbal aggression, and girls on indirect aggression. Girls were socially more skillful than boys in the use of peaceful means of conflict resolution (they scored higher on constructive conflict resolution and third‐party intervention). The attributional discrepancy index (ADI) scores were negative for all three types of aggression in both sexes. Verbal aggression is apparently more condemned in boys than in girls. ADI scores were positive for constructive conflict resolution and third‐party intervention in both genders, being higher in boys. In girls, verbal aggression was positively correlated with popularity. In both sexes, popularity showed a positive correlation with constructive conflict resolution and third‐party intervention, and a negative correlation with withdrawal and victimization. Boys who liked school were popular with same‐sex peers and scored higher on constructive conflict resolution. Girls who liked school were less aggressive according to peer rating. They also rated higher on conflict resolution and third‐party intervention. Physical aggression was related to age. The results are discussed in a cross‐cultural perspective. Aggress. Behav. 33:170–183, 2007. © 2007 Wiley‐Liss, Inc.
Highly crystalline activated layered double hydroxides as solid acid‐base catalysts
Authors: Lei Xiaodong , Zhang Fazhi , Yang Lan , Guo Xiaoxiao , Tian Yuanyuan , Fu Shanshan , Li Feng , Evans David G. , Duan Xue
Published: February 2007

Activated layered double hydroxides (LDHs) with high crystallinity, obtained by calcination/rehydration of LDH precursors synthesized by urea decomposition, have higher catalytic activity in acetone self‐condensation and Knoevenagel reactions than less crystalline materials obtained from LDH precursors synthesized by titration co‐precipitation. The activated LDHs possess both basic and acidic sites. High resolution transmission electron microscopy (HRTEM) confirms that the highly crystalline activated LDHs retain the lattice structure of the LDH precursors with lattice parameters a = b = 0.31 ± 0.01 nm and α = 60 ± 2°. An acid‐base catalytic mechanism has been proposed to interpret the catalytic behavior based on the fact that acid‐base hydroxyl group pairs on the activated LDH surface have a separation of 0.31 nm. It is proposed that the active sites are mainly located on the ordered array of hydroxyl sites on the basal surfaces rather than on the edges, as has been previously suggested. © 2007 American Institute of Chemical Engineers AIChE J, 2007
Craniofacial anomalies, humero‐radial synostosis, rhizomelic limb shortness: Previously unrecognized autosomal recessive syndrome
Authors: Al‐Hassnan Zuhair N. , Teebi Ahmad S.
Published: February 2007

Humero‐radial synostosis (HRS) is a rare skeletal anomaly that might be seen in some craniosynostosis syndromes, notably Antley–Bixler syndrome, and in other disorders in association with skeletal anomalies. Here we report on two daughters of first cousin Saudi parents with syndromic HRS. Both patients had distinctive craniofacial features including cranium bifidum occultum, hypertelorism, epicanthus inversus, capillary hemangiomata, and malformed ears. Musculoskeletal examination revealed rhizomelic shortness with normal hands and feet. Skeletal survey showed bilateral HRS with no evidence of craniosynostosis. The craniofacial manifestations in these two patients do not match any of the syndromes known to be associated with HRS. We consider that the constellation is unique and apparently represents a previously unrecognized syndrome. © 2007 Wiley‐Liss, Inc.
First trimester ultrasonography in screening and detection of fetal anomalies
Authors: Sonek Jiri
Published: February 2007

An obstetrical ultrasound examination provides invaluable information regarding the fetus. Until the mid‐1980s, ultrasound in the first trimester was limited to localization of the pregnancy, establishing viability, and accurate dating. With the advent of high‐resolution ultrasound and transvaginal scanning, a significant amount of information about the fetus can be gained and provided to the patient at a very early stage in gestation. This article provides an overview of the role of first trimester (11–13 + 6 weeks' gestation) ultrasound in screening and diagnosis of fetal anomalies. The first trimester is an ideal time for screening for aneuploidy, primarily due to the advantages that nuchal translucency (NT) measurement provides. NT measurement is also useful in establishing the risk of congenital cardiac disorders and a number of genetic and non‐genetic syndromes. Significant NT thickening is associated with an increase in perinatal morbidity and mortality. Potential mechanisms resulting in increased NT are discussed. A number of new ultrasound markers for fetal aneuploidy have been investigated over the past several years, some of which appear to improve the screening efficacy of early ultrasonography. The role of these is reviewed. A number of fetal anomalies can now be consistently diagnosed in the first trimester. Their appearance at this early gestational age is discussed as well. It is clear that, data obtained by first trimester ultrasound are useful in counseling expectant parents and in planning the appropriate follow‐up. © 2007 Wiley‐Liss, Inc.
The inhibitive effect of poly(p‐toluidine) on corrosion of iron in 1M HCL solutions
Authors: Manivel P. , Venkatachari G.
Published: February 2007

In recent years, polymer amines have been recognized as an excellent corrosion inhibitors for iron in acid solutions. In this work, the inhibitive effect of p‐toluidine and poly(p‐toluidine) on corrosion of iron in 1M HCl has been studied by the electrochemical methods such as impedance, linear polarization, Tafel polarization techniques. The effectiveness of poly(p‐toluidine) was found to be high in comparison with that of monomer. The results showed that p‐toluidine and poly(p‐toluidine) suppressed both cathodic and anodic processes of iron dissolution in 1M HCl. The inhibition efficiency of both p‐toluidine and poly(p‐toluidine) were found to increase with the inhibitor concentrations. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Eosinophilic fasciitis in a rhesus macaque
Authors: Anderson Scott T. , Klein Edwin C.
Published: February 2007

Eosinophilic fasciitis (EF) is an inflammatory disorder in the category of scleroderma‐like connective tissue diseases. There are no animal models for spontaneously occurring EF. We present the case of a rhesus macaque (Macaca mulatta) with clinical, laboratory, and histologic features of EF.
Precision of the larsen and the sharp methods of assessing radiologic change in patients with rheumatoid arthritis
Authors: Cuchacovich Miguel , Couret Marie , Peray Pascals , Gatica HÉCtor , Sany Jacques
Published: February 2007

Objective. To compare the sensitivity of Sharp's and Larsen's radiographic scoring methods for detecting change in rheumatoid arthritis (RA) over time.

Methods. Radiographs of the hands and wrists were taken at the beginning and at the end of a 2‐year followup period, in 42 patients with active RA. Films were scored blindly using both scoring methods. Patients were under treatment with methotrexate (intramuscular injections).

Results. Radiographic evidence of progression or amelioration was detected in 25 patients by Larsen's method and in 35 patients by Sharp's method. The relative sensitivity to change over time was greater for Sharp's method (0.01 < P < 0.025).

Conclusion. Sharp's radiographic scoring method seems to be more sensitive to change over time than is Larsen's method. The clinical importance of the change needs to be definitively established.
Antibodies in raheumatoid synovial fluids bind to a restricted series of protein antigens in rheumatoid synovial tissue
Authors: Lafyatis Robert , Flipo Rene M. , Duquesnoy Bernard , Capron Andre
Published: February 2007

Objective. By searching the synovial fluid of patients with rheumatoid arthritis (RA) for antibodies that react to protein antigens in synovial tissue, we sought to identify putative antigens present in RA synovial tissue that might drive the pathologic immune response believed to be responsible for the joint inflammation.

Methods. Synovial tissue was homogenized in sodium dodecyl sulfate polyacrylamide gel buffer, electrophoresed, and analyzed by immunoblotting.

Results. Antibodies from synovial fluids of patients with RA bound to several proteins in rheumatoid synovial tissues, including a series of low (27.5‐, 29‐, and 30‐kd), middle (43‐ and 53‐kd), and high (140‐, 164‐, and 182‐kd) molecular weight proteins. Most of these antigens were also detected in normal synovial tissue, and the high molecular weight proteins were also present in normal dermal, muscle, and liver tissues. The low and middle molecular weight proteins were detected in some, but not all, of the other normal tissues and in Jurkat cell lysates. Antibodies to the low and high series of proteins were present in all rheumatoid synovial fluids tested, but were generally absent from synovial fluids from patients with other arthritic diseases.

Conclusion. These results show that antibodies in synovial fluids consistently react to several proteins in RA and normal synovial tissues. These antigens are possibly the same antigens provoking the T cell response in RA; therefore, understanding the mechanism of the immune response against these proteins will likely lead to important insight into the etiology of RA.
The effect of interleukin‐1 on cytokine gene expression in cultured human articular chondrocytes analyzed by messenger rna phenotyping
Authors: Seid Janet M. , Rahman Shamim , Graveley Robert , Bunning Rowena A. D. , Nordmann Rene , Wishart William , Graham Russell R.
Published: February 2007

Objective. To investigate the pattern of cytokine gene expression in human articular chondrocytes in culture in response to interleukin‐1β (IL‐1β). The effect of serum and variations in culture conditions was also studied.

Methods. Messenger RNA was extracted from cells, reverse‐transcribed to complementary DNA, and amplified by the polymerase chain reaction (PCR), using specific oligonucleotide primers. The PCR products were validated by restriction analysis with specific enzymes and by Southern blot analysis.

Results. In cultured articular chondrocytes, IL‐1β, IL‐1α, granulocyte colony‐stimulating factor (CSF), and granulocyte‐macrophage CSF cytokine genes were expressed only after induction by IL‐1β. However, IL‐6, IL‐8, and macrophage CSF genes were expressed constitutively. The expression of IL‐1β was dose and time dependent.

Conclusion. Using PCR, it was possible to demonstrate gene expression for several cytokines in human articular chondrocytes in culture. It was evident that some cytokine genes were expressed constitutively and some were inducible by IL‐1β.
The measurement of collagenase, tissue inhibitor of metalloproteinases (timp), and collagenase—timp complex in synovial fluids from patients with osteoarthritis and rheumatoid arthritis
Authors: Clark I. M. , Powell L. K. , Ramsey S. , Hazleman B. L. , Cawston T. E.
Published: February 2007

Objective. To compare the levels of collagenase, tissue inhibitor of metalloproteinases (TIMP), and collagenase—TIMP complex in synovial fluid (SF) from patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA). This study aims to clarify existing data from previously used enzyme or inhibitor activity assays performed following separation by gel filtration, by using a 1‐step enzyme‐linked immunosorbent assay (ELISA) for each component.

Methods. Total collagenase, free TIMP, and collagenase—TIMP complex were measured using a newly developed, specific double‐antibody sandwich ELISA.

Results. Levels of both collagenase and TIMP were significantly higher in RA patients (collagenase 1,560 ± 150 ng/ml [mean ± SEM], TIMP 1,610 ± 130 ng/ml; n = 80) than OA patients (collagenase 420 ± 90 ng/ml, TIMP 1,050 ± 60 ng/ml; n = 80), with the difference being especially striking for collagenase. Sixteen RA fluids had detectable levels of collagenase—TIMP complex, compared with only 3 OA fluids.

Conclusion. The level of total collagenase in SF is greater in RA than OA, while levels of free TIMP show more overlap between the 2 diseases; this may simply reflect the increased inflammation seen in RA, or it may reflect a different disease mechanism.
Inclusion body myositis and renal cell carcinoma. report of two cases and review of the literature
Authors: Ytterberg Steven R. , Roelofs Robert I. , Mahowald Maren L.
Published: February 2007

Objective. To describe the clinical course of 2 patients with concurrent inclusion body myositis and renal cell carcinoma and review published reports of inclusion body myositis associated with malignancy.

Methods. Prospective followup of 2 patients. Review of published case reports and series of patients with inclusion body myositis.

Results. Our 2 patients with inclusion body myositis and renal cell carcinoma had no improvement of strength following nephrectomy. Seven previously reported cases of inclusion body myositis and malignancy were identified and are discussed.

Conclusion. Findings in our 2 patients suggest that there is no etiopathologic relationship between inclusion body myositis and malignancy.
Cancer in systemic sclerosis
Authors: Abu‐Shakra Mahmoud , Guillemin Francis , Lee Peter
Published: February 2007

Objective. To determine whether the frequency of cancer is increased among patients with systemic sclerosis (SSc).

Methods. A retrospective chart review of 248 patients who were followed up prospectively was conducted.

Results. Cancers developed in 18 patients (7.3%) during 2,001 patient‐years at risk. The most frequent types were cancers of the lung (7 patients) and breast (5 patients). Older age at diagnosis of SSc was a significant risk factor for cancer. Lung cancer was associated with the presence of pulmonary fibrosis. The age‐standardized incidence rate for all cancers (7.9/1,000) was 2.1 times the overall rate in the Ontario population (P > 0.0001).

Conclusion. The frequency of cancer is increased in patients with SSc.
Suppression of human cartilage proteoglycan synthesis by rheumatoid synovial fluid mononuclear cells activated with mycobacterial 60‐kd heat‐shock protein
Authors: Wilbrink B. , Holewijn M. , Bijlsma J. W. J. , Van Roy J. L. A. M. , Den Otter W. , Van Eden W.
Published: February 2007

Objective. To examine whether T cell reactivity toward heat‐shock proteins (HSP) contributes to cartilage destruction in rheumatoid arthritis (RA).

Methods. An in vitro system was used, in which human cartilage explants were cocultured with hsp60‐activated synovial fluid mononuclear cells (SFMC) from patients with RA, and proteoglycan (PG) synthesis was measured.

Results. The hsp60‐activated SFMC suppressed cartilage PG synthesis. This effect was dependent on the production of interleukin‐1 (IL‐1) and tumor necrosis factor α (TNFα).

Conclusion. Mycobacterial 60‐kd heat‐shock protein can activate rheumatoid SFMC to suppress human cartilage PG synthesis. This suppression is mediated by IL‐1 and TNFα.
Evaluation of the european spondylarthropathy study group preliminary classification criteria in alaskan eskimo populations
Authors: Boyer Georgiana S. , Templin David W. , Goring Wendell P.
Published: February 2007

Objective. To evaluate the preliminary classification criteria proposed by the European Spondylarthropathy Study Group (ESSG) in Alaskan Eskimo populations.

Methods. We examined, interviewed, and reviewed the records of 104 Eskimo patients with spondylarthropathy and 75 with other rheumatic disorders, and evaluated them according to the proposed criteria.

Results. We found an overall sensitivity of 88.5% and a specificity of 89.3%, which is similar to the reported values in European populations.

Conclusion. The ESSG criteria performed well in a population very different from that in which they were developed, and deserve further evaluation as a much‐needed and useful epidemiologic tool.
Nucleosome‐specific antibody from an autoimmune mrl/mp‐lpr/lpr mouse
Authors: Losman Julie A. , Fasy Thomas M. , Novick Kristine E. , Massa Margherita , Monestier Marc
Published: February 2007

Objective. To characterize the binding properties and variable‐region sequences of LG4‐1, a monoclonal antibody from an autoimmune MRL/Mp‐lpr/lpr mouse that reacts specifically with nucleosome core particles and represents a new antinuclear antibody specificity.

Methods. The reactivity of the antibody against various nuclear substrates was determined using an enzymatic immunoassay, and the variable‐region genes were sequenced from messenger RNA, using the dideoxy chain termination method.

Results. LG4‐1 was found to react with nucleosome core particles but not with individual histones and DNA, or with various histone–histone and histone–DNA complexes. It was demonstrated that this antibody is encoded by a combination of variable‐region genes and gene segments that have undergone few somatic mutations.

Conclusion. The nucleosome core particle expresses a unique conformational autoepitope(s) resulting from the ordered association of histones and DNA.
Labial salivary gland biopsy is a reliable test for the diagnosis of primary and secondary amyloidosis. a prospective clinical and immunohistologic study in 59 patients
Authors: Hachulla Eric , Janin Anne , Flipo René Marc , Saïle Rachid , Facon Thierry , Bataille Dominique , Vanhille Philippe , Hatron Pierre‐Yves , Devulder Bernard , Duquesnoy Bernard
Published: February 2007

Objective. Reports of the detection of amyloidosis by labial salivary gland (LSG) biopsy have been mostly anecdotal. The aim of this study was to assess the value of this method in the diagnosis of amyloidosis.

Methods. LSG biopsy tissues were studied with a combination method using Congo red stain and immunohistologic characterization using an antibody directed against the serum amyloid P (SAP) component. Electron microscopy was performed in all cases. In a prospective study, we evaluated 30 patients with biopsy‐proven AA or AL amyloidosis. We compared these patients with a control group of 29 age‐matched patients without clinical or biologic evidence of amyloid disease (14 had rheumatoid arthritis and 15 had plasma cell dyscrasia).

Results. In 26 of the 30 patients with known systemic amyloidosis, amyloid deposits were identified on LSG biopsy (sensitivity of 86%). In 1 of the remaining patients, amyloid deposits were identified on LSG biopsy and systemic amyloidosis was confirmed by abdominal fat biopsy and 123I‐labeled SAP scintigraphy.

Conclusion. This study emphasizes the high sensitivity of LSG biopsy in the diagnosis of amyloidosis, even in the absence of oral symptoms.
Spontaneous production of epstein‐barr virus by b lymphoblastoid cell lines obtained from patients with sjögren's syndrome. possible involvement of a novel strain of epstein‐barr virus in disease pathogenesis
Authors: Tateishi Mutsuto , Saito Ichiro , Yamamoto Kohtaro , Miyasaka Nobuyuki
Published: February 2007

Objective. To investigate the involvement of Epstein‐Barr virus (EBV) in the pathogenesis of Sjögren's syndrome (SS) and to examine whether the spontaneous production of EBV is unique to SS B cell lines.

Methods. B cell lines were established from peripheral blood mononuclear cells (PBMC) of patients with systemic lupus erythematosus, rheumatoid arthritis, and SS. The cord blood immortalization assay, flow cytometric analysis, and polymerase chain reaction (PCR) were used to detect EBV production by B cell lines.

Results. SS B cell lines produced EBV at a higher frequency, and in significantly larger amounts, than did other B cell lines. However, no correlation with the amount of EBV DNA in the genome of B cell lines was found. PCR analysis revealed that EBV with a B95‐8–like U2 region was dominant in SS B cell lines.

Conclusion. Spontaneous, massive production of EBV by B cell lines is unique to SS, and may contribute to the polyclonal B cell activation seen in this disease.
Comparative studies of the major histocompatibility complex in french canadian and non–french canadian caucasians with systemic lupus erythematosus
Authors: Goldstein Rose , Sengar Dharmendra P. S.
Published: February 2007

Objective. To investigate and compare the predisposing role of major histocompatibility complex (MHC) genes in systemic lupus erythematosus (SLE) in French Canadian and non–French Canadian (mainly Anglo‐Saxon descent) Caucasian subjects.

Methods. HLA–A, B, C (serology), DR, and DQ (restriction fragment length polymorphism [RFLP] typing) were determined. RFLP defining a large C4A,21‐OHA deletion (Taq I C4) and an Nco I tumor necrosis factor α (TNFα) RFLP were analyzed in 91 Caucasian Canadians and 91 ethnically matched control subjects.

Results. In the total SLE and non–French Canadian SLE populations, HLA–B8, DR3(DR17), Dw24, DQ2, and the C4A gene deletion were associated with SLE. These HLA specificities and the C4A gene deletion were not significantly increased in French Canadian SLE patients compared with ethnically matched controls. When present in French Canadians, the C4A gene deletion was less closely associated with HLA–DR3(DR17), Dw24, DQ2 than in other Caucasians. HLA–DQ6 was associated with SLE in French Canadians. No association of the 2‐allele Nco I TNFα RFLP with SLE was found in this population, in either ethnic group.

Conclusion. These results support the importance of ethnic background in the study of MHC genes and SLE. The extended HLA–B8,DR3,C4A null haplo‐type is found mainly in SLE patients of Anglo‐Saxon descent, while the DQ6 specificity is associated with SLE in French Canadians. This relatively genetically homogeneous Caucasian population offers the opportunity to study non–HLA–B8,DR3–linked MHC influence in SLE.
Synergistic effect of interleukin‐1β and tumor necrosis factor α on interleukin‐8 gene expression in synovial fibroblasts. evidence that interleukin‐8 is the major neutrophil‐activating chemokine released in response to monokine activation
Authors: Rathanaswami Palaniswami , Hachicha Mohamed , Wong Wai Lee , Schall Thomas J. , Mccoll Shaun R.
Published: February 2007

Objective. To investigate both the involvement of chemokines in general and the relative importance of specific chemokines in rheumatoid arthritis (RA), we characterized the effect of the monokines tumor necrosis factor α (TNFα) and interleukin‐1β (IL‐1β) on the synthesis of neutrophil‐activating factors by synovial fibroblasts isolated from the joints of patients with RA.

Methods. Neutrophil‐stimulating activity was assessed by determining intracellular calcium mobilization. IL‐8 synthesis and secretion was assessed by specific enzyme‐linked immunosorbent assay, and IL‐8 messenger RNA (mRNA) levels were determined by Northern blot.

Results. Treatment of synovial fibroblasts with IL‐1β and TNFα resulted in the production of an activity which induced intracellular calcium mobilization in peripheral blood neutrophils. The 2 monokines combined had a synergistic effect on the release of the neutrophil‐stimulating activity. The effect of the 2 monokines required gene transcription and translation, and closely mimicked the pattern of IL‐8 secretion induced in these cells by the monokines. We confirmed that the majority of the neutrophil‐stimulating activity was IL‐8 by 3 different approaches: cross‐desensitization experiments with IL‐8, melanoma growth‐stimulatory activity, and neutrophil‐activating peptide 2, stimulation of calcium mobilization in cells transfected with the IL‐8 receptor complementary DNA, and inhibition of the activity following pretreatment of the supernatants with an anti‐IL‐8 antibody. TNFα and IL‐1β induced a time‐ and dose‐dependent release of immunoreactive IL‐8. A synergistic effect of TNFα and IL‐1β was also observed for both IL‐8 production and accumulation of IL‐8 mRNA.

Conclusion. These results indicate that the monokines TNFα and IL‐1β synergistically activate IL‐8 expression and protein secretion by synovial fibroblasts, and that under these conditions, IL‐8 appears to be the major neutrophil‐activating factor released.
In vitro release of prostaglandins and leukotrienes from synovial tissue, cartilage, and bone in degenerative joint diseases
Authors: Wittenberg Ralf H. , Willburger Roland E. , Kleemeyer Karin S. , Peskar Bernhard A.
Published: February 2007

Objective. To determine the major source of eicosanoid release in arthritic joint tissues and to examine the modulation of this release by indomethacin and diclofenac.

Methods. Release of prostaglandin E2 (PGE2), 6‐keto‐PGF1α, leukotriene B4 (LTB4), and LTC4 was measured in supernatants of synovial tissue, cartilage, and bone incubates from patients with osteoarthritis, active rheumatoid arthritis (RA), inactive RA, and pseudogout. Radioimmunoassay (RIA) was used to determine the levels of the eicosanoids.

Results. Addition of the divalent cation ionophore A23187 resulted in significant release of all eicosanoids measured from synovial tissue, but not from cartilage, cortical bone, or cancellous bone. PG release was significantly inhibited by the addition of indomethacin or diclofenac at either 10–5 moles/liter or 10–7 moles/liter. The amount of LTC4 released from cartilage and bone was only slightly above the detection limit of the RIA, whereas large amounts were released from synovial tissue. Neither indomethacin nor diclofenac had an effect on LTC4 release. LTC4 release from synovial tissue of patients with inactive RA was significantly decreased in comparison with the levels from synovial tissue of patients with the other joint diseases. There was no significant difference in PG release among patients in the various disease groups.

Conclusion. Synovial tissue appears to be the major source of eicosanoids in synovial fluid. Indomethacin and diclofenac inhibit the release of PG, but not LT, from various joint tissues.
The course of skin involvement in systemic sclerosis over three years in a trial of chlorambucil versus placebo
Authors: Clements Philip , Lachenbruch Peter , Furst Daniel , Paulus Harold
Published: February 2007

Objective. To describe the course of cutaneous involvement in systemic sclerosis (SSc; scleroderma) over 3 years, in the context of a placebo‐controlled drug trial.

Methods. The course of skin tethering (assessed by a semiquantitative skin scoring technique) was documented annually for 3 years in 64 SSc patients with early (< 3 years duration at entry), intermediate (3–8 years duration), or late (>8 years duration) diffuse or limited SSc.

Results. Mean ± SD entry skin scores were significantly greater in the 33 diffuse SSc patients (13.1 ± 5.0) than in the 31 limited SSc patients (4.3 ± 2.1) (P < 0.001). In patients with diffuse SSc, the skin score remained stable for the first 12 months, but had decreased significantly by 24 months (P < 0.022) and 36 months (P < 0.004). In those with limited SSc, the skin score did not change significantly over 3 years.

Conclusion. Trials of treatments designed to affect skin thickening/tethering should be conducted in patients who have diffuse SSc (of short, intermediate, or long duration) at entry. The best time to study therapies designed to affect skin thickening may be in the first year after entry.