bluuebunny/crossref_metadata_2025 huggingface dataset:
Income-Specific Trends in Obesity in Brazil: 1975–2003
Authors: Monteiro Carlos A. , Conde Wolney L. , Popkin Barry M.
Published: August 2007

Objectives. We sought to update income-specific secular trends in obesity in Brazil to assess the hypothesis that the disease burden is shifting toward the poor.

Methods. We compared overall and income-specific obesity prevalence rates estimated for Brazilian men and women from national surveys conducted in 1975, 1989, and 2003. We calculated age-adjusted prevalence ratios to assess time trends.

Results. In the first 14-year period examined (1975–1989), obesity rates among men and women increased by 92% and 63%, respectively, and increases were relatively higher among individuals in lower income groups. In the second 14-year period (1989–2003), there were further increases in obesity among men, and again increases were larger among the poor. In this second period, the obesity rate remained virtually stable in the overall female population, but it increased by 26% among women in the 2 lower income quintiles and decreased by 10% among women in the 3 higher income quintiles.

Conclusions. The burden of obesity is shifting toward the poor and can no longer be considered a disease of the socioeconomic elite. Policymakers need to design policy and programs that reach all members of society, but especially the poor.
Effects of Genetic Variation in the Human Retinol Binding Protein-4 Gene (RBP4) on Insulin Resistance and Fat Depot–Specific mRNA Expression
Authors: Kovacs Peter , Geyer Michaela , Berndt Janin , Klöting Nora , Graham Timothy E. , Böttcher Yvonne , Enigk Beate , Tönjes Anke , Schleinitz Dorit , Schön Michael R. , Kahn Barbara B. , Blüher Matthias , Stumvoll Michael
Published: August 2007

OBJECTIVE— Serum retinol binding protein 4 (RBP4) is a new liver- and adipocyte-derived signal that may contribute to insulin resistance. Therefore, the RBP4 gene represents a plausible candidate gene involved in susceptibility to type 2 diabetes.

RESEARCH DESIGN AND METHODS— In this study, the RBP4 gene was sequenced in DNA samples from 48 nonrelated Caucasian subjects. Five novel and three known single nucleotide polymorphisms (SNPs) were identified. Furthermore, five recently reported SNPs were genotyped in 90 subjects. Six SNPs, representative of their linkage disequilibrium groups, were then genotyped in 934 diabetic and 716 nondiabetic subjects.

RESULTS— A haplotype of six common SNPs (A-G-G-T-G-C) was significantly increased in 934 case subjects with type 2 diabetes compared with 537 healthy control subjects with normal glucose tolerance (P = 0.02; odds ratio 1.37 [95% CI 1.05–1.79]). Furthermore, in the cohort of 716 nondiabetic Caucasian subjects, carriers of the A-G-G-T-G-C haplotype had significantly higher mean fasting plasma insulin and 2-h plasma glucose than subjects without the haplotype. Two single SNPs (rs10882283 and rs10882273) were also associated with BMI, waist-to-hip ratio, and fasting plasma insulin, and several SNPs were associated with circulating free fatty acids (all adjusted P < 0.05). In addition, subjects carrying a previously reported diabetes-associated haplotype had significantly higher mRNA levels in visceral adipose tissue (adjusted P < 0.05) in a subgroup of nondiabetic subjects (n = 170) with measurements of RBP4 mRNA expression in visceral and subcutaneous fat depots.

CONCLUSIONS— Our data indicate a role of RBP4 genetic variation in susceptibility to type 2 diabetes and insulin resistance, possibly through an effect on RBP4 expression.
Increased Hepatic CD36 Expression Contributes to Dyslipidemia Associated With Diet-Induced Obesity
Authors: Koonen Debby P.Y. , Jacobs René L. , Febbraio Maria , Young Martin E. , Soltys Carrie-Lynn M. , Ong Huy , Vance Dennis E. , Dyck Jason R.B.
Published: August 2007

OBJECTIVE—The etiology of type 2 diabetes often involves diet-induced obesity (DIO), which is associated with elevated plasma fatty acids and lipoprotein associated triglycerides. Since aberrant hepatic fatty acid uptake may contribute to this, we investigated whether increased expression of a fatty acid transport protein (CD36) in the liver during DIO contributes to the dyslipidemia that precedes development of type 2 diabetes.

RESEARCH DESIGN AND METHODS—We determined the effect DIO has on hepatic CD36 protein expression and the functional consequence of this in terms of hepatic triglyceride storage and secretion. In addition, in vivo adenoviral gene delivery of CD36 to the livers of lean mice was performed to determine if increased hepatic CD36 protein was sufficient to alter hepatic fatty acid uptake and triglyceride storage and secretion.

RESULTS—During DIO, CD36 protein levels in the liver are significantly elevated, and these elevated levels correlate with increased hepatic triglyceride storage and secretion. These alterations in liver lipid storage and secretion were also observed upon forced expression of hepatic CD36 in the absence of DIO and were accompanied with a marked rise in hepatic fatty acid uptake in vivo, demonstrating that increased CD36 expression is sufficient to recapitulate the aberrant liver lipid handling observed in DIO.

CONCLUSIONS—Increased expression of hepatic CD36 protein in response to DIO is sufficient to exacerbate hepatic triglyceride storage and secretion. As these CD36-mediated effects contribute to the dyslipidemia that often precedes the development of type 2 diabetes, increased hepatic CD36 expression likely plays a causative role in the pathogenesis of type 2 diabetes.
Finite Element Analysis of Nonuniformity of Tires with Imperfections
Authors: Jeong K. M. , Kim K. W. , Beom H. G. , Park J. U.
Published: August 2007

The effects of variations in stiffness and geometry on the nonuniformity of tires are investigated by using the finite element analysis. In order to evaluate tire uniformity, a three-dimensional finite element model of the tire with imperfections is developed. This paper considers how imperfections, such as variations in stiffness or geometry and run-out, contribute to detrimental effects on tire nonuniformity. It is found that the radial force variation of a tire with imperfections depends strongly on the geometrical variations of the tire.
Validation of a Steady-State Transport Analysis for Rolling Treaded Tires
Authors: Qi J. , Herron J. R. , Sansalone K. H. , Mars W. V. , Du Z. Z. , Snyman M. , Surendranath H.
Published: August 2007

A new computational procedure for the analysis of treaded tires under conditions of steady-state rolling has been recently developed. As with well-known procedures for axisymmetric structures, the new procedure uses a mixed Eulerian/Lagrangian kinematic description in which rigid body rotation is described in an Eulerian manner and the deformation is described in a Lagrangian manner. This work discusses the industrial and historical context of the procedure, provides an overview of the technology, reviews experimental validation targets, and compares against better-established procedures. The new procedure successfully predicts the distributions of normal, lateral, and longitudinal stress in several different cases. A limitation of the new procedure is that solution accuracy can degrade, particularly in the longitudinal stress, when the angular extent of the base pitch sector is too large. When applied in nontreaded cases, the new procedure produces results consistent with established procedures such as Lagrangian rolling and conventional steady-state transport for axisymmetric structures. The main benefits of the new procedure are (1) computational efficiency and (2) the ability to include the full geometry of treaded tires.
A Finite Element Approach to the Transient Dynamics of Rolling Tires with Emphasis on Rolling Noise Simulation
Authors: Brinkmeier Maik , Nackenhorst Udo , Volk Heiner
Published: August 2007

The sound radiating from rolling tires is the most important source of traffic noise in urban regions. In this contribution a detailed finite element approach for the dynamics of tire/road systems is presented with emphasis on rolling noise prediction. The analysis is split into sequential steps, namely, the nonlinear analysis of the stationary rolling problem within an arbitrary Lagrangian Eulerian framework, and a subsequent analysis of the transient dynamic response due to the excitation caused by road surface roughness. Here, a modal superposition approach is employed using complex eigenvalue analysis. Finally, the sound radiation analysis of the rolling tire/road system is performed.
Inelastic Fracture Mechanics for Tire Durability Simulations
Authors: Kaliske Michael , Näser Bastian , Meiners Christian
Published: August 2007

A fully three-dimensional fracture mechanical approach is introduced which may serve as a basis for tire durability simulations utilizing the finite element method. The so-called material force approach is employed as an elegant alternative characterization of the energy release rate or the J-integral to describe discrete cracks. As a vector quantity, it even yields directional information. The method is applicable in the context of finite strains and nonlinear elasticity and inelasticity. Using the shown approach, a physical and efficient modeling of fracture sensitivity of tires is obtained.
Weak Records
Authors: Stepanov Alexei
Published: August 2007

In this survey, we discuss major developments of the past decades in the study on weak records.
Bread and Other Baked Products
Authors: Sievert Dietmar , Hoseney R. Carl , Delcour Jan A.
Published: August 2007

The article contains sections titled:

1.

Introduction

2.

Wheat Types and their Uses

3.

Wheat Breeding and Biotechnology

3.1.

Traditional Breeding

3.2.

Biotechnology

4.

Milling of Wheat

5.

Wheat Flour

5.1.

Flour Constituents

5.1.1.

Starch

5.1.2.

Protein

5.1.3.

Lipids

5.1.4.

Nonstarch Polysaccharides (NSP)

5.1.5.

Ash

5.2.

Chemical Flour Treatments

6.

Evaluation of Flours

6.1.

Physical Dough Tests

6.1.1.

Mixing Curves

6.1.2.

Flour Strength

6.2.

α‐Amylase Activity

7.

Dough Formation

7.1.

Underlying Mechanisms of Dough Formation

7.2.

Role of Proteins in Dough Formation

7.3.

Thermodynamic View of Dough Mixing

7.4.

Aeration of Dough during Mixing

8.

Role of Bread Ingredients

9.

Bread and Dough Making Processes

9.1.

Straight Dough

9.2.

Sponge and Dough

9.3.

Liquid Preferments

9.4.

No‐Time Processes

9.5.

Sour Dough

9.6.

Frozen Dough

10.

Gas Production and Retention

10.1.

Leavening Mechanisms

10.2.

Fermentation and Gas Production by Yeast

10.3.

Gas Production by Chemical Leavening

10.4.

Gas Retention

11.

Molding and Proofing

12.

Baking

12.1.

Transformation of Dough into Bread

12.2.

Crumb Grain Formation

12.3.

Crust Formation

12.4.

Changes of Flour Constituents

13.

Flavor of Baked Products

14.

Glass Transition and its Role in Baking

15.

Bread Varieties and Speciality Breads

16.

Soft Wheat Products

16.1.

Technology of Cookie and Cracker Production

16.2.

Cookies

16.2.1.

Cookie Types

16.2.2.

Underlying Mechanisms of Cookie Baking

16.2.2.1.

Texture Development of Cookies

16.2.2.2.

Development of the Cookie Surface Pattern

16.3.

Crackers

16.4.

Wafers

16.5.

American Biscuits

16.6.

Cakes

16.6.1.

Cake Making and Underlying Mechanisms of Cake Baking

16.6.2.

Role of Cake Ingredients

16.7.

Pastries

16.7.1.

Short Pastry

16.7.2.

Puff Pastry

17.

Retention of Baked Product Quality

17.1.

Staling

17.2.

Microbial Spoilage

17.2.1.

Retention of Quality

17.2.2.

Chemical Preservatives

18.

Trends in Baking

18.1.

U.S. Bakery Market

18.2.

Western European Bakery Market

18.3.

Consumer Demands and Product Trends

This keyword provides information on the different aspects of the industrial conversion of cereal grains (predominantly wheat) into final baked products. The emphasis is on bread systems, but cookie, cake, and pastry products are also dealt with. The different wheat types and their classification systems, the milling process, and the flour constituents are described. The quality criteria of flour and their assessment are dealt with, different aspects of dough formation are discussed and a description of different bread making processes follows. The important aspect of gas production by yeast, chemical leavening or by other means is discussed as are the transformations during the baking process.
Milk and Dairy Products
Authors: Jost Rolf
Published: August 2007

The article contains sections titled:1.Introduction2.Historical Aspects3.Composition of Milk3.1.Milk Fat3.1.1.Composition3.1.2.Properties of Fat Globules3.2.Milk Proteins3.2.1.Major Nitrogen Fractions in Milk3.2.2.Nomenclature and Properties of Cow's Milk Proteins3.2.3.Caseins3.2.4.Whey Proteins3.2.5.Nonprotein Nitrogen (NPN)3.3.Lactose3.4.Minerals3.5.Vitamins3.6.Contaminants4.Physical and Physicochemical Properties of Milk5.Microbiology of Milk6.Nutritional Value of Milk6.1.Milk as a Nutrient Source for Humans6.2.Health Aspects of Milk Consumption7.Dairy Technology7.1.Milk Production and Transport7.2.Pretreatment in Dairies7.3.Thermal Treatment7.3.1.Thermal Processes7.3.2.Effects of Heat on Milk7.3.2.1.Effect on Microorganisms7.3.2.2.Inactivation of Milk Enzymes7.3.2.3.Heat‐Induced Destruction of Nutrients7.4.Homogenization7.5.Separation Processes7.5.1.Microfiltration7.5.2.Ultrafiltration7.5.3.Nanofiltration and Reverse Osmosis7.5.4.Ion Exchange Processes7.5.5.Electrodialysis7.6.Cleaning and Disinfection7.7.Water Treatment8.Fluid Milk8.1.Consumer's Milk8.1.1.Legal Classes of Consumer's Milk8.1.2.Characterization According to Heat Treatment8.1.3.Modified Consumer's Milks8.1.4.Packaging of Fluid Milks and Milk Products8.2.Reconstituted and Recombined Milk9.Milk Products9.1.Flavored Milk and Milk Beverages9.2.Evaporated (Condensed) Milk9.2.1.Technology of Concentration by Evaporation9.2.2.Unsweetened Condensed Milk9.2.3.Sweetened Condensed Milk9.3.Dry Milk Products9.3.1.Drying Processes9.3.2.Whole and Skim Milk Powders9.3.3.Butter and Buttermilk Powders9.3.4.Whey Powders and Permeates9.3.5.Milk Protein Powders9.3.6.Powdered Infant Formulas9.4.Fermented Milk Products9.4.1.Legal Definitions9.4.2.Specific Fermented Products9.5.Cream9.5.1.Production9.5.2.Types of Cream9.6.Butter9.6.1.Production9.6.2.Steps in Buttermaking9.7.Anhydrous Milk Fat and Butter Oil9.8.Dairy Spreads9.9.Dairy Desserts10.Quality Control11.Legislation12.Economic Aspects13.Acknowledgement
Prostaglandins
Authors: Buchmann Bernd , Rehwinkel Hartmut
Published: August 2007

The article contains sections titled:

1.History2.Structure, Nomenclature, and Physical Properties3.Occurrence and Biosynthesis4.Pharmacological Effects and Uses5.Syntheses

Prostaglandins are formed fromarachidonic acid. Those and all other derivatives of arachidonic acid, e.g., prostacyclins, thromboxanes, leukotrienes, and lipoxines are called eicosanoids. Most eicosanoids are chemically and metabolically unstable. Therefore, many pharmaceutical companies have tried to improve the stability by modifying the original structures. Several of these analogues have already reached the market in different therapeutic indications or show promising results in clinical trials. This article describes the chemical and pharmacological properties of the natural derivatives and their analogues as well as the synthetic access to some of the natural compounds.
Assembly of Nanoparticle Patterns with Single‐Particle Resolution Using DNA‐Mediated Charge Trapping Technique: Method and Applications
Authors: Lin H.‐Y. , Tsai L.‐C. , Chen C.‐D.
Published: August 2007

We report a unique approach for producing one‐dimensional gold‐nanoparticle patterns with single‐particle resolution in which the linewidth is only limited by the particle size. In this approach, a focused electron beam was first utilized to generate a positive charge layer on a SiO2 surface. Biotinated DNA molecules attracted by these positive charges were subsequently used to grasp Au‐nanoparticles revealing the e‐beam exposure patterns. Due to repulsive force between Au colloidal particles, the particles in the single‐line patterns were orderly separated. We further show that the single‐line patterns hold potential in nano‐photonics and nano‐electronics. For the latter, we demonstrate that the line patterns can serve as a template for conductive nanowires of high or low resistance. While low resistance wires showed linear current–voltage characteristics with an extremely high maximum allowed current density, the high resistance wires exhibited charging effect with clear Coulomb oscillation behavior at low temperatures. This demonstrates that the technique is capable of producing interconnects as well as single‐electron‐transistors, and opens up possibilities for fabrication of integrated circuits.
Macro and microscopic CH4–CO2 replacement in CH4 hydrate under pressurized CO2
Authors: Ota Masaki , Saito Takeomi , Aida Tsutomu , Watanabe Masaru , Sato Yoshiyuki , Smith Richard L. , Inomata Hiroshi
Published: August 2007

CH4–CO2 replacement in CH4 hydrate with high pressure CO2 was studied with in‐situ laser Raman spectroscopy at 273.2 K and at initial pressures of 3.2, 5.4, and 6.0 MPa. Replacement rates increased with increasing pressures up to 3.6 MPa and did not change at higher pressures (∼6.0 MPa). These results showed that the replacement rates were dependent on pressure and phase conditions with the driving force being strongly related to fugacity differences of the two guest components between fluid and hydrate phases. When CH4 hydrate was contacted with CO2 under flow conditions, in‐situ Raman measurements of the hydrate phase showed differences of cage decomposition rates between the Medium‐cage (M‐cage) and the Small‐cage (S‐cage) in the CH4 hydrate with decomposition of the M‐cage being faster than that of the S‐cage. The van der Waals–Platteeuw model was applied to the measurements of the transient data and it is shown that the theory allows estimation of occupancies of each component during replacement. © 2007 American Institute of Chemical Engineers AIChE J, 2007
Role of prothrombin complex concentrates in reversing warfarin anticoagulation: A review of the literature
Authors: Leissinger Cindy A. , Blatt Philip M. , Hoots W. Keith , Ewenstein Bruce
Published: August 2007

Over‐anticoagulation is a common problem with warfarin therapy and can lead to major or life‐threatening bleeding. The goal of urgent warfarin reversal is to elevate or replace vitamin K‐dependent clotting factors. In the United States, fresh frozen plasma (FFP) is considered the standard of care for warfarin reversal. Prothrombin complex concentrates (PCCs) offer an alternative to FFP for rapidly replacing deficient clotting factors and correcting the international normalized ratio (INR). However, few prospective clinical trials have been conducted to evaluate the effectiveness of these concentrates relative to other treatment modalities. A review of the published literature over the last 30 years found that PCCs offer a rapid and specific method for replacing vitamin K‐dependent clotting factors and restoring normal hemostasis in the context of over‐coagulation. In those studies in which PCCs were compared with FFP, PCCs were found more effective in shortening the time to INR correction and were associated with a low risk of thrombotic adverse events. Evidence‐based treatment guidelines are needed to optimize the use of PCCs for warfarin reversal. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.
Block copolymers of N‐vinyl carbazole and α,ω‐dihydroxy polydimethylsiloxane
Authors: Akar Ahmet , Kizilcan Nilgun , Ustamehmetoglu Belkis , Colak Demet , Sarac A. Sezai , Colak Cengiz
Published: August 2007

The redox system of ceric ammonium nitrate (Ce4+) and α,ω‐dihydroxy polydimethylsiloxane (DH.PDMS) was used to polymerize N‐vinyl carbazole (NVCz) to produce poly(N‐vinylcarbazole)‐b‐α,ω‐dihydroxy polydimethylsiloxane(PNVCz‐b‐DH.PDMS). The ratio of NVCz/ceric salt/DH.PDMS has an important effect on the properties of formed copolymers. White insulating PNVCz‐b‐PDMS copolymers with high fluorescence intensity are produced if the ratio of ceric salt/ NVCz is below 0.2. Green conductive PNVCz‐b‐PDMS copolymers are produced if this ratio is well above 0.2. The concentration and the type of DH.PDMS affected the polymerization yield. PNVCz‐b‐DH.PDMS copolymers were also prepared by electroinduced polymerization in the presence of catalytic amount of Ce4+ in a divided electrochemical cell where Ce3+ is readily oxidized to Ce4+ at the anode. White insulating PNVCz‐b‐DH.PDMS copolymers show higher contact angle value and lower Tg values than of white poly(N‐vinyl carbazole) (PNVCz). © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Mechanical and morphological study of polyphenylene sulfide/liquid crystalline polymer blends compatibilized with a maleic anhydride grafted copolymer
Authors: Rath T. , Kumar S. , Mahaling R. N. , Das C. K. , Yadaw S. B.
Published: August 2007

Blends of thermotropic liquid crystalline polymer (LCPA‐950), based on a copolyester of hydroxynapthoic acid and hydroxybenzoic acid with an engineering thermoplastic, poly(phenylene sulfide) (PPS), were prepared using a corotating twin‐screw extruder. Addition of a third component, a functionalized polypropylene (maleic anhydride grafted polypropylene, MA‐PP), that interact with the thermotropic liquid crystalline polymer (TLCP) facilitates the structural development of the TLCP phase by acting as a compatibilizer at the interface. Differential scanning calorimetry and dynamic mechanical thermal analysis results, however, show that there is an interaction between the polymers in the presence of compatibilizer. This means that MA‐PP can be used as a compatibilizer for the PPS/LCP in situ composite system. The viscosity of the compatibilized in situ composite was decreased by the compatibilizer, and this is mainly due to the fibrous structure of the LCP at the high shear rate. The mechanical properties of the ternary blends were increased when a proper amount of MA‐PP was added. This is attributed to fine fibril generation induced by the addition of MA‐PP. Morphological observations determined the significance of the third component in immiscible polymer blends, and an optimum amount of MA‐PP exists for the best mechanical performance. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007
Compositional trend analysis on poly(phenylene ether) based thermoplastic elastomers
Authors: Gupta Samik , Krishnamurthy Raja , Biswas Amit , Bhowmick Anil K.
Published: August 2007

Detailed statistical trend analysis of thermoplastic elastomers based on poly (phenylene ether) (PPE), polystyrene (PS), ethylene vinyl acetate (EVA) and styrene‐ethylene‐butylene‐styrene (SEBS) was done through Design Expert software by Stat‐Ease. D optimal crossed design was followed to capture the interaction with the parameters. Effect of blend ratio, vinyl acetate (VA) content of EVA, molecular weight (MW) of SEBS and intrinsic viscosity (IV) of PPE on the blend performance (response) was studied in detail. Design of Experiment (DOE) analysis showed the “optimized formulation” of the blend. Increase in PPE‐polystyrene (PS) content increased tensile strength and modulus of the blend, followed by a decrease in strain at break. However, EVA had a reverse effect on tensile strength and modulus. Strain at break increased significantly with increasing SEBS content in the blend. Graphical and numerical optimization showed that superior mechanical properties (tensile strength, strain at break and modulus) could be achieved at VA content ∼ 50% at a particular loading of EVA. Low MW SEBS was found to be more compatible with the other components of the blend. Mechanical properties of the quaternary blend were marginally affected with change in IV of PPE in the range of 0.33 to 0.46. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007
Kinetics of the copolymerization of alkylene oxides with glycidyl methacrylate
Authors: Ahmetli Gulnare , Kocak Ahmet , Yazicigil Zafer
Published: August 2007

In the present study, the kinetics of copolymerization reaction of propylene oxide (PO) and butylene oxide (BO) with glycidyl methacrylate (GMA) in the presence of BF3·O(C2H5)2 catalyst were investigated. The kinetic parameters and activation energy of the copolymerization reaction were calculated. The amounts of reacting PO, BO, and GMA during copolymerization were determined by chromatographic method, because the same copolymerization conditions were carried out for them. It was determined that the copolymerization rate of PO (r0) and BO (r0) was higher than that of GMA, but activation energy (E) of GMA was higher than that of PO and BO. The rate of reaction, the rate constant, and activation energy were calculated from the amount of copolymer obtained with respect to time. The structures of synthesized copolymers were determined by the spectral and chemical analysis methods. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007
Estimating required habitat size for fish conservation in streams
Authors: Cowley David E.
Published: August 2007

A procedure is described to estimate viable population size and the area of habitat needed to support an endangered stream fish population. Monte Carlo simulations were used to evaluate population fates with stochastic demography and random variation simulated to cause age class 0 failures in some years. Viable population was defined in this paper to be large enough to have less than a 10% chance of extinction in 100 years and to have a long‐term effective size of at least 500 breeding adults, although the method could be applied for any assumed extinction rate and effective size.

Using data for Rio Grande cutthroat trout (Oncorhynchus clarkii virginalis) in an age class model, it was inferred from simulations that minimum viable population size was 2750 fish, which would require 2.2 ha of habitat at median density of the subspecies in New Mexico streams.

Minimum viable population size occurred at the highest survival rate of young of year and no population‐wide year class failures. Viable population size, and hence required habitat size, increased as the failure rate for age class 0 increased or when the survival rate from age 0 to 1 declined. This suggested that managers should avoid managing for smallest possible viable population size and instead plan for much larger population sizes to accommodate temporal variation in demography and habitat quality.

Decreased survival rate of young of year caused the stable age class distribution to be skewed toward the age class 0, which profoundly reduced effective population size. This suggested that habitat restoration that improves survival of young of year would be a good strategy to increase effective size over the long term.

Estimating required habitat size could improve introductions of fish to create new populations. Although requiring time‐consuming simulations, the procedure can be used to estimate required habitat size for any species for which population and demographic data are available.

Copyright © 2007 John Wiley & Sons, Ltd.
Serious infection following anti–tumor necrosis factor α therapy in patients with rheumatoid arthritis: Lessons from interpreting data from observational studies
Authors: Dixon W. G. , Symmons D. P. M. , Lunt M. , Watson K. D. , Hyrich K. L. , Silman A. J.
Published: August 2007

Objective

In a recent observational study, we found that the risk of serious infection following anti–tumor necrosis factor α (anti‐TNFα) therapy in patients with rheumatoid arthritis (RA) was not importantly increased compared with the background risk in routinely treated RA patients with similar disease severity. Observational data sets are, however, subject to a number of important biases related to selection factors for the timing of starting and stopping therapy. Infection risk is also likely to vary with duration of therapy. This study was undertaken to examine the influences of these biases and of the method of analysis on the risk of infection.

Methods

We compared the risk of serious infection in 8,659 patients treated with anti‐TNFα with that in 2,170 patients treated with traditional disease‐modifying antirheumatic drugs (DMARDs) recruited to the British Society for Rheumatology Biologics Register. We applied a number of statistical models in which we varied the length of the followup period by using different definitions of the date of discontinuation of treatment and different lag periods of risk following drug cessation.

Results

When the at‐risk period was defined as “receiving treatment”, the adjusted incidence rate ratio comparing patients receiving anti‐TNFα therapy with patients receiving DMARD therapy was 1.22 (95% confidence interval [95% CI] 0.88–1.69). Limiting followup to the first 90 days, however, revealed an adjusted incidence rate ratio of 4.6 (95% CI 1.8–11.9). Rates of infection were increased in the 90 days immediately following drug discontinuation and beyond, explained by selection factors for drug discontinuation.

Conclusion

These findings show that overall, the way in which UK rheumatologists select patients for starting and discontinuing anti‐TNFα therapy explains our previous finding of no increase in risk. However, there may be important increases in true risk, notably early in the course of treatment, that would become more evident depending on the definition of at‐risk period.
Reduction in the incidence of myocardial infarction in patients with rheumatoid arthritis who respond to anti–tumor necrosis factor α therapy: Results from the British Society for Rheumatology Biologics Register
Authors: Dixon W. G. , Watson K. D. , Lunt M. , Hyrich K. L. , Silman A. J. , Symmons D. P. M.
Published: August 2007

Objective

Rheumatoid arthritis (RA) is associated with an increased risk of coronary artery disease, possibly acting via shared mechanisms of inflammation. This study was undertaken to test the hypothesis that the powerful antiinflammatory effect of anti–tumor necrosis α (anti‐TNFα) therapy might lead to a reduction in the incidence of myocardial infarction (MI) in patients with RA.

Methods

Using data from the British Society for Rheumatology Biologics Register, a national prospective observational study, we compared MI rates in 8,670 patients with RA treated with anti‐TNFα and 2,170 patients with active RA treated with traditional disease‐modifying antirheumatic drugs (DMARDs).

Results

Through July 2006, 63 MIs occurred in the anti‐TNFα cohort during 13,233 person‐years of followup and 17 MIs occurred in the DMARD cohort during 2,893 person‐years of followup, equivalent to a rate of 4.8 events per 1,000 person‐years and 5.9 events per 1,000 person‐years, respectively. After adjustment for baseline risk factors, there was no reduction in the rate of MI in the anti‐TNFα cohort compared with the DMARD cohort (incidence rate ratio 1.44 [95% confidence interval 0.56–3.67]). In an analysis of anti‐TNFα–treated patients who responded to the treatment within 6 months versus those who did not, MI rates were found to be 3.5 events per 1,000 person‐years in responders and 9.4 events per 1,000 person‐years in nonresponders. The adjusted incidence rate ratio (95% confidence interval) for responders compared with nonresponders was 0.36 (0.19–0.69).

Conclusion

These results indicate that RA patients treated with anti‐TNFα do not have a lower incidence of MI compared with RA patients treated with traditional DMARDs. However, the risk of MI is markedly reduced in those who respond to anti‐TNFα therapy by 6 months compared with nonresponders. This finding supports the notion that inflammation plays a pivotal role in MI.
Low molecular weight isoforms of the aggrecanases are responsible for the cytokine‐induced proteolysis of aggrecan in a porcine chondrocyte culture system
Authors: Powell Alison J. , Little Christopher B. , Hughes Clare E.
Published: August 2007

Objective

The major proteases responsible for aggrecan turnover in articular cartilage are the aggrecanases (ADAMTS‐4 and ADAMTS‐5). Although several studies have demonstrated C‐terminal truncation of these aggrecanases, the mechanism and importance of this processing are poorly understood. The objective of this study was to further investigate ADAMTS‐4 and ADAMTS‐5 C‐terminal truncation in a porcine model in vitro culture system.

Methods

Chondrocyte–agarose cultures with well‐established extracellular matrices were treated with or without interleukin‐1 (IL‐1), for a variety of different culture time periods. Cultures were analyzed for release of sulfated glycosaminoglycan, aggrecanase‐generated interglobular domain (IGD)–aggrecan cleavage, and the presence of ADAMTS‐4 and ADAMTS‐5 isoforms. Inhibition of aggrecanase activity with monoclonal antibodies, tissue inhibitor of metalloproteinases 3 (TIMP‐3), and cycloheximide pretreatment were used to identify ADAMTS isoforms involved in IGD–aggrecan catabolism.

Results

Multiple isoforms, including possible zymogens, of ADAMTS‐4 and ADAMTS‐5 were sequestered within the extracellular matrix formed by 3‐week chondrocyte–agarose cultures. IL‐1 exposure induced production of a low molecular weight (37 kd) isoform of ADAMTS‐4. This isoform was capable of degrading exogenous aggrecan at the IGD–aggrecanase site, was inhibited by TIMP‐3, was blocked after preincubation with an antibody to a sequence in the catalytic domain of ADAMTS‐4, and required de novo synthesis in the presence of IL‐1 for its generation.

Conclusion

In porcine chondrocyte–agarose cultures, a 37‐kd ADAMTS‐4 isoform appears to be the major matrix protease responsible for the IGD–aggrecanase activity detected in response to exposure to IL‐1. This conclusion contradicts that of recent studies of transgenic knockout mice and highlights the need to determine the roles of the different aggrecanase(s) in human disease.
Protein isoprenylation regulates secretion of matrix metalloproteinase 1 from rheumatoid synovial fibroblasts: Effects of statins and farnesyl and geranylgeranyl transferase inhibitors
Authors: Abeles Aryeh M. , Marjanovic Nada , Park Jean , Attur Mukundan , Chan Edwin S. , Al‐Mussawir Hayf E. , Dave Mandar , Fisher Mark C. , Stuchin Steven A. , Abramson Steven B. , Pillinger Michael H.
Published: August 2007

Objective

To determine whether protein prenylation (farnesyl/geranylgeranylation) regulates matrix metalloproteinase (MMP) secretion from rheumatoid arthritis (RA) synovial fibroblasts (RASFs), and whether MMP‐1 secretion can be regulated by statins or prenyltransferase inhibitors via effects mediated by ERK, JNK, and NF‐κB.

Methods

RASFs obtained from patients during elective knee replacement surgery were assessed by immunoblotting and/or enzyme‐linked immunosorbent assay for secretion of MMP‐1 and MMP‐13 in the presence of tumor necrosis factor α (TNFα), interleukin‐1β (IL‐1β), statins, the farnesyl transferase (FT) inhibitor FTI‐276 and geranylgeranyl transferase inhibitor GGTI‐298, and prenyl substrates (farnesyl pyrophosphate [FPP] and geranylgeranyl pyrophosphate [GGPP]). Activities of JNK and ERK were determined by phosphoimmunoblotting, and NF‐κB activation was determined by nuclear translocation of the p65 component.

Results

FTI‐276, but not statins, inhibited RASF secretion of MMP‐1, but not MMP‐13, following induction with TNFα (P = 0.0007) or IL‐1β (P = 0.006). Loading RASFs with FPP to promote farnesylation enhanced MMP‐1 secretion. FTI‐276 inhibited activation of JNK (P < 0.05) and NF‐κB (P = 0.02), but not ERK. In contrast, GGTI‐298 enhanced, while GGPP inhibited, MMP‐1 secretion. FTI‐276 and GGTI‐298 together had no effect on MMP‐1 secretion. Stimulation of RASFs with TNFα or IL‐1β led to increased expression and activity of FT.

Conclusion

Protein farnesylation is required for expression and secretion of MMP‐1 from RASFs, via effects on JNK and NF‐κB. The ability of cytokines to stimulate the expression and activity of FT suggests that FT may be increased in the rheumatoid joint. In contrast, geranylgeranylation down‐regulates MMP‐1 expression. Statins simultaneously inhibit farnesylation and geranylgeranylation, and in consequence do not inhibit MMP‐1 secretion. The ability of FTI‐276 to inhibit MMP‐1 secretion suggests a potential therapeutic strategy in RA.
Pre–B cell colony‐enhancing factor/visfatin, a new marker of inflammation in rheumatoid arthritis with proinflammatory and matrix‐degrading activities
Authors: Brentano Fabia , Schorr Olivier , Ospelt Caroline , Stanczyk Joanna , Gay Renate E. , Gay Steffen , Kyburz Diego
Published: August 2007

Objective

To study possible mechanisms that mediate induction of the recently described adipocytokine pre–B cell colony‐enhancing factor (PBEF) in joints of patients with rheumatoid arthritis (RA), and to analyze whether levels of PBEF correlate with disease severity and whether PBEF itself has the potential to act as a proinflammatory and destructive mediator in RA.

Methods

RA synovial fibroblasts (RASFs) and monocytes were stimulated with Toll‐like receptor (TLR) ligands, cytokines, and recombinant human PBEF or were transfected with PBEF expression constructs or with PBEF‐specific small interfering RNA. Production of interleukin‐6 (IL‐6), IL‐8, and tumor necrosis factor α (TNFα) was measured by enzyme‐linked immunosorbent assay, and expression of matrix metalloproteinases (MMPs) was assessed by real‐time polymerase chain reaction. PBEF expression in synovial tissue, synovial fluid, serum, and SFs was assessed by immunohistochemistry, in situ hybridization, Western blotting, and enzyme immunoassays.

Results

In RASFs, PBEF was up‐regulated by TLR ligands and cytokines that are characteristically present in the joints of patients with RA. In synovial tissue, RASFs were the major PBEF‐expressing cells. A predominance of PBEF was found in the synovial lining layer and at sites of invasion into cartilage. Levels of PBEF in serum and synovial fluid correlated with the degree of inflammation and clinical disease activity. Moreover, PBEF itself activated the transcription factors NF‐kB and activator protein 1 and induced IL‐6, IL‐8, MMP‐1, and MMP‐3 in RASFs as well as IL‐6 and TNFα in monocytes. PBEF knockdown in RASFs significantly inhibited basal and TLR ligand–induced production of IL‐6, IL‐8, MMP‐1, and MMP‐3.

Conclusion

Our findings establish PBEF as a proinflammatory and destructive mediator of joint inflammation in RA and identify PBEF as a potential therapeutic target.
Adapted versions of the Sharp/van der Heijde score are reliable and valid for assessment of radiographic progression in juvenile idiopathic arthritis
Authors: Ravelli Angelo , Ioseliani Maka , Norambuena Ximena , Sato Juliana , Pistorio Angela , Rossi Federica , Ruperto Nicolino , Magni‐Manzoni Silvia , Ullmann Nicola , Martini Alberto
Published: August 2007

Objective

To develop adapted versions of the Sharp/van der Heijde radiographic scoring system for use in juvenile idiopathic arthritis (JIA), and to investigate their validity in JIA patients with polyarticular disease.

Methods

The study group comprised 177 patients with polyarticular JIA. Radiographs of the wrist/hand of each patient were obtained at baseline (first observation) and then at 1, 3, 5, 7/8, and 10 years and were assessed independently by 2 pediatric rheumatologists according to different adaptations of the Sharp/van der Heijde method. To facilitate score assignment, the radiograph for each patient was compared with a bone age–related standard. Validation procedures included analysis of reliability, construct validity, and score progression over time.

Results

Interobserver and intraobserver agreement on longitudinal score values and score changes was good for all of the adapted scoring versions (intraclass correlation coefficient >0.85). Score changes over time were moderately to strongly correlated with the clinical indicators of long‐term joint damage and with the amount of long‐term radiographic damage as measured with the carpo:metacarpal ratio, thereby demonstrating good construct validity. A steady increase in scores over time was observed, with joint space narrowing being the most common form of damage throughout the disease course. The inclusion of 5 new areas appeared to increase the overall construct validity of erosion scores.

Conclusion

Our results show that the adapted versions of the Sharp/van der Heijde score are reliable and valid for the assessment of radiographic progression in patients with JIA.
Inhibition of toll‐like receptor 4 breaks the inflammatory loop in autoimmune destructive arthritis
Authors: Abdollahi‐Roodsaz Shahla , Joosten Leo A. B. , Roelofs Mieke F. , Radstake Timothy R. D. J. , Matera Giovanni , Popa Calin , van der Meer Jos W. M. , Netea Mihai G. , van den Berg Wim B.
Published: August 2007

Objective

Degeneration of extracellular matrix of cartilage leads to the production of molecules capable of activating the immune system via Toll‐like receptor 4 (TLR‐4). The objective of this study was to investigate the involvement of TLR‐4 activation in the development and progression of autoimmune destructive arthritis.

Methods

A naturally occurring TLR‐4 antagonist, highly purified lipopolysaccharide (LPS) from Bartonella quintana, was first characterized using mouse macrophages and human dendritic cells (DCs). Mice with collagen‐induced arthritis (CIA) and mice with spontaneous arthritis caused by interleukin‐1 receptor antagonist (IL‐1Ra) gene deficiency were treated with TLR‐4 antagonist. The clinical score for joint inflammation, histologic characteristics of arthritis, and local expression of IL‐1 in joints were evaluated after treatment.

Results

The TLR‐4 antagonist inhibited DC maturation induced by Escherichia coli LPS and cytokine production induced by both exogenous and endogenous TLR‐4 ligands, while having no effect on these parameters by itself. Treatment of CIA using TLR‐4 antagonist substantially suppressed both clinical and histologic characteristics of arthritis without influencing the adaptive anti–type II collagen immunity crucial for this model. Treatment with TLR‐4 antagonist strongly reduced IL‐1β expression in articular chondrocytes and synovial tissue. Furthermore, such treatment inhibited IL‐1–mediated autoimmune arthritis in IL‐1Ra−/− mice and protected the mice against cartilage and bone pathology.

Conclusion

In the present study, we demonstrate for the first time that inhibition of TLR‐4 suppresses the severity of experimental arthritis and results in lower IL‐1 expression in arthritic joints. Our data suggest that TLR‐4 might be a novel target in the treatment of rheumatoid arthritis.
Varus foot alignment and hip conditions in older adults
Authors: Gross K. Douglas , Niu Jingbo , Zhang Yu Qing , Felson David T. , McLennan Christine , Hannan Marian T. , Holt Kenneth G. , Hunter David J.
Published: August 2007

Objective

Mechanical strain on the hip can result from varus malalignment of the foot. This study was undertaken to explore the cross‐sectional relationship between varus foot alignment and hip conditions in a population of older adults.

Methods

The Framingham Osteoarthritis Study cohort consists of a population‐based sample of older adults. Within this sample, we measured forefoot and rearfoot frontal plane alignment using photographs of a non–weight‐bearing view of both feet of 385 men and women (mean age 63.1 years). Each foot segment was categorized according to the distribution of forefoot and rearfoot alignment among cases of ipsilateral hip pain, trochanter tenderness, hip pain or tenderness, and total hip replacement (THR). The relationship of foot alignment to these conditions was examined using logistic regression and generalized estimating equations, adjusting for age, body mass index, sex, and physical activity.

Results

The mean ± SD rearfoot varus alignment was 0.7 ± 5.5 degrees, and the mean ± SD forefoot varus alignment was 9.9 ± 9.9 degrees. Subjects in the highest category of forefoot varus alignment had 1.8 times the odds of having ipsilateral hip pain (P for trend = 0.06), 1.9 times the odds of having hip pain or tenderness (P for trend < 0.01), and 5.1 times the odds of having undergone THR (P for trend = 0.04) compared with those in the lowest category. No significant associations were found between rearfoot varus alignment and any hip conditions.

Conclusion

Forefoot varus malalignment may be associated with ipsilateral hip pain or tenderness and THR in older adults. These findings have implications for treatment, since this risk factor is potentially modifiable with foot orthoses.
Circulating C3 is necessary and sufficient for induction of autoantibody‐mediated arthritis in a mouse model
Authors: Monach Paul A. , Verschoor Admar , Jacobs Jonathan P. , Carroll Michael C. , Wagers Amy J. , Benoist Christophe , Mathis Diane
Published: August 2007

Objective

For the inflammation characteristic of rheumatoid arthritis, the relative contribution of mediators produced locally in the synovium versus those circulating systemically is unknown. Complement factor C3 is made in rheumatoid synovium and has been proposed to be a crucial driver of inflammation. The aim of this study was to test, in a mouse model of rheumatoid arthritis, whether C3 synthesized within the synovium is important in promoting inflammation.

Methods

Radiation bone marrow chimeras between normal and C3−/− mice were constructed in order to generate animals that expressed or lacked expression of C3 only in hematopoietic cells. Parabiotic mice were made by surgically linking C3−/− mice to irradiated wild‐type mice to obtain animals having C3 only in the circulation. Arthritis was induced by injection of serum from arthritic K/BxN mice.

Results

In bone marrow chimeras, synthesis of C3 by radioresistant cells was necessary and sufficient to confer susceptibility to serum‐transferred arthritis. Parabionts having C3 only in the circulation remained sensitive to arthritis induction, and the cartilage of these arthritic mice contained deposits of C3.

Conclusion

In a mouse model in which the alternative pathway of complement activation is critical to the induction of arthritis by autoantibodies, circulating C3 was necessary and sufficient for arthritis induction.
Identification of a novel autoantibody directed against small ubiquitin‐like modifier activating enzyme in dermatomyositis
Authors: Betteridge Zoë , Gunawardena Harsha , North Jean , Slinn Jenna , McHugh Neil
Published: August 2007

Objective

Myositis‐specific autoantibodies (MSAs) are directed against cell machinery proteins such as aminoacyl–transfer RNA synthetases, signal recognition particle, Mi‐2, and CADM‐140. Because serologic subsets can define patients with specific clinical manifestations, the identification of further MSAs may help to identify additional disease subsets within the myositis spectrum.

Methods

Sera from 20 adult patients with dermatomyositis (DM) were screened for autoantibodies. Two patients were further characterized due to the presence of the same novel immunoprecipitation (IP) pattern on sodium docecyl sulfate–polyacrylamide gel electrophoresis (SDS‐PAGE) and similar clinical manifestations. Both patients presented with cutaneous disease, followed by proximal myositis 6 months later. Both patients had associated nonspecific interstitial pneumonia but no signs of malignancy. The novel targets were identified using a combination of IP, SDS‐PAGE, and matrix‐assisted laser desorption ionization–time‐of‐flight mass spectrometry.

Results

Indirect HEp‐2 immunofluorescence on sera from both patients displayed a diffuse, coarse, speckled, nucleolar‐sparing pattern. IP revealed the presence of previously uncharacterized bands at ∼40 kd and ∼90 kd in both patients. The novel targets were identified as the small ubiquitin‐like modifier 1 (SUMO‐1) activating enzyme A subunit and SUMO‐1 activating enzyme B subunit.

Conclusion

These findings reveal previously uncharacterized autoantibodies directed against a protein involved in posttranslational modification, the SUMO activating enzyme, in 2 patients with DM who had similar clinical features, including severe skin disease and interstitial pneumonia.
A Theoretical Study of the Structure and Thermochemical Properties of Alkali Metal Fluoroplumbates MPbF3
Authors: Boltalin A. I. , Korenev Yu. M. , Sipachev V. A.
Published: August 2007

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