bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosis and management of non‐anti‐D red cell antibodies in pregnancy
Authors: Gajjar Ketan , Spencer Chris
Published: April 2009

Anti‐D prophylaxis has reduced the incidence of haemolytic disease of the newborn.

A variety of non‐anti‐D red cell antibodies can cause a degree of neonatal haemolysis.

The frequency of antibody testing should be individualised.

Management of non‐anti‐D alloimmunisation should be aimed at minimising perinatal morbidity.

Learning objectives:

To understand the causes and risk factors for maternal non‐anti‐D antibodies.

To learn when to initiate invasive testing in the antenatal period.

To know when to deliver the baby to maximise perinatal outcome.

To learn about which antibodies can cause fetal hydrops and intrauterine haemolysis.

Ethical issues:

When is it necessary to perform paternal blood tests to determine red cell antibody status?

When should the mother be delivered in cases where the red cell antibody detected has a weak association with neonatal haemolysis?

Please cite this article as: Gajjar K, Spencer C. Diagnosis and management of non‐anti‐D red cell antibodies in pregnancy. The Obstetrician & Gynaecologist 2009;11:89–95.
Primary and secondary cytomegalovirus in pregnancy
Authors: McCarthy Fergus P , Jones Cheryl , Rowlands Shelley , Giles Michelle
Published: April 2009

Cytomegalovirus is the commonest cause of congenital viral infection in developed countries.

Infection is asymptomatic in 90% of individuals.

Forty percent of pregnant women with primary infection transmit it to their fetus.

Ten percent of infants with congenital cytomegalovirus display clinical manifestations at birth and are at risk of neurological sequelae.

While routine antenatal testing is not currently recommended, congenital infection remains a significant obstetric management problem.

Learning objectives:

To learn about the incidence, diagnosis and sequelae of cytomegalovirus in pregnancy.

To become familiar with treatment options for the management of congenital cytomegalovirus.

Ethical issues:

Should practitioners recommend routine cytomegalovirus screening in pregnancy?

Is a randomised controlled trial necessary before offering treatment with hyperimmune globulin for congenital cytomegalovirus?

Please cite this article as: McCarthy FP, Jones C, Rowlands S, Giles M. Primary and secondary cytomegalovirus in pregnancy. The Obstetrician & Gynaecologist 2009;11:96–100.
How to set up a perineal clinic
Authors: Fowler G , Williams A , Murphy G , Taylor K , Wood C , Adams E
Published: April 2009

All women sustaining obstetric anal sphincter injury should be reviewed at 6–12 weeks postpartum.

All women with anal incontinence should be offered endoanal ultrasound, anorectal physiology testing and review by a clinician with experience in anal sphincter injury.

A perineal clinic provides the setting for debriefing and provision of consistent, accurate information from clinicians with a special interest in sphincter injury.

Learning objectives:

To be aware of the benefits of a perineal clinic.

To learn how to set up a perineal clinic.

Ethical issues:

Should anorectal testing be a routine part of the follow‐up of all women after anal sphincter injury or restricted to symptomatic women?

Who is responsible for debriefing women sustaining anal sphincter injury?

Please cite this article as: Fowler G, Williams A, Murphy G, Taylor K, Wood C, Adams E. How to set up a perineal clinic. The Obstetrician & Gynaecologist 2009;11:129–132.
Intra-articular Injected Synovial Stem Cells Differentiate into Meniscal Cells Directly and Promote Meniscal Regeneration Without Mobilization to Distant Organs in Rat Massive Meniscal Defect
Authors: Horie Masafumi , Sekiya Ichiro , Muneta Takeshi , Ichinose Shizuko , Matsumoto Kenji , Saito Hirohisa , Murakami Takashi , Kobayashi Eiji
Published: April 2009

Osteoarthritis in the knees, which can be caused by meniscal defect, constitutes an increasingly common medical problem. Repair for massive meniscal defect remains a challenge owing to a lack of cell kinetics for the menisci precursors in knee joint. The synovium plays pivotal roles during the natural course of meniscal healing and contains mesenchymal stem cells (MSCs) with high chondrogenic potential. Here, we investigated whether intra-articular injected synovium-MSCs enhanced meniscal regeneration in rat massive meniscal defect. To track the injected cells, we developed transgenic rats expressing dual luciferase (Luc) and LacZ. The cells derived from synovium of the rats demonstrated colony-forming ability and multipotentiality, both characteristics of MSCs. Hierarchical clustering analysis revealed that gene expression of meniscal cells was closer to that of synovium-MSCs than to that of bone marrow-MSCs. Two to 8 weeks after five million Luc/LacZ+ synovium-MSCs were injected into massive meniscectomized knee of wild-type rat, macroscopically, the menisci regenerated much better than it did in the control group. After 12 weeks, the regenerated menisci were LacZ positive, produced type 2 collagen, and showed meniscal features by transmission electron microscopy. In in-vivo luminescence analysis, photons increased in the meniscus-resected knee over a 3-day period, then decreased without detection in all other organs. LacZ gene derived from MSCs could not be detected in other organs except in synovium by real-time PCR. Synovium-MSCs injected into the massive meniscectomized knee adhered to the lesion, differentiated into meniscal cells directly, and promoted meniscal regeneration without mobilization to distant organs.

Disclosure of potential conflicts of interest is found at the end of this article.
Characterization of DLK1+ Cells Emerging During Skeletal Muscle Remodeling in Response to Myositis, Myopathies, and Acute Injury
Authors: Andersen Ditte C. , Petersson Stine J. , Jørgensen Louise H. , Bollen Peter , Jensen Pernille B. , Teisner Børge , Schroeder Henrik D. , Jensen Charlotte H.
Published: April 2009

Delta like 1 (DLK1) has been proposed to act as a regulator of cell fate determination and is linked to the development of various tissues including skeletal muscle. Herein we further investigated DLK1 expression during skeletal muscle remodeling. Although practically absent in normal adult muscle, DLK1 was upregulated in all human myopathies analyzed, including Duchenne- and Becker muscular dystrophies. Substantial numbers of DLK1+ satellite cells were observed in normal neonatal and Duchenne muscle, and furthermore, myogenic DLK1+ cells were identified during muscle regeneration in animal models in which the peak expression of Dlk1 mRNA and protein coincided with that of myoblast differentiation and fusion. In addition to perivascular DLK1+ cells, interstitial DLK1+ cells were numerous in regenerating muscle, and in agreement with colocalization studies of DLK1 and CD90/DDR2, qPCR of fluorescence-activated cell sorting DLK1+ and DLK1− cells revealed that the majority of DLK1+ cells isolated at day 7 of regeneration had a fibroblast-like phenotype. The existence of different DLK1+ populations was confirmed in cultures of primary derived myogenic cells, in which large flat nonmyogenic DLK1+ cells and small spindle-shaped cells coexpressing DLK1 and muscle-specific markers were observed. Myogenic differentiation was achieved when sorted DLK1+ cells were cocultured together with primary myoblasts revealing a myogenic potential that was 10% of the DLK1− population. Transplantation of DLK1+ cells into lacerated muscle did, however, not give rise to DLK1+ cell-derived myofibers. We suggest that the DLK1+ subpopulations identified herein each may contribute at different levels/time points to the processes involved in muscle development and remodeling.

Disclosure of potential conflicts of interest is found at the end of this article.
Cistromics of hormone-dependent cancer
Authors: Lupien Mathieu , Brown Myles
Published: April 2009

Alterations in transcription programs are a fundamental feature of cancer. Nuclear receptors, such as the estrogen receptor alpha (ERα) and androgen receptors (ARs), are central in this process as they can directly impact gene expression through interaction with the chromatin and subsequent association with coregulators and the transcriptional machinery. Unbiased genome-wide investigations have demonstrated the predominant recruitment of both ERα and AR to distant (non-promoter)-regulatory elements. Furthermore, these studies revealed a clear relationship between sites of transcription factor recruitment and gene regulation. Indeed, expression profiles from AR-positive primary prostate tumors and cell lines directly relate to the AR cistrome in prostate cancer cells, while the ERα cistrome in breast cancer cells relates to expression profiles from ERα-positive primary breast tumors. Additionally, cell-type-specific ERα cistromes are linked to lineage-specific estrogen-induced expression profiles in different cell types, for example osteosarcoma and breast cancer cells. The pioneer factor forkhead box A1 (FoxA1/HNF3α) plays a central role in AR and ERα signaling. It is recruited in a lineage-specific manner translating the epigenetic signature consisting of mono- and dimethylated histone H3 on lysine 4 (H3K4me1/me2) into functional regulatory elements. Hence, through the interplay between the pioneer factor, namely FoxA1, and epigenetic events, the transcriptional potential of a given cell lineage is predefined. Since this directly impacts signaling through nuclear receptors, these discoveries should significantly impact the development of novel therapeutic strategies directed against multiple types of cancer.
Numerical study of straight-bladed Darrieus-type tidal turbine
Authors: Dai Y. M. , Lam W.
Published: April 2009

This paper presents developments in numerical simulations of a cross-flow vertical-axis marine current turbine (straight-bladed Darrieus type) with particular emphasis on rotor-performance prediction and hydrodynamic loads for structural design calculations. This study initially used theoretical double-multiple-streamtube models, followed by physical testing on a scaled-down model turbine and primarily numerical simulations. Numerical investigations of a proposed full-scale turbine (power coefficient, blade loads and flow behaviour) were undertaken using the developed computational models. The turbine design was studied using a time-accurate Reynolds-averaged Navier–Stokes (RANS) commercial solver. A transient-rotor-stator model with a moving mesh technique was used to capture the change in flow field at a particular time step. A shear stress-transport [Formula: see text] turbulence model was used to model turbulent features of the flow. The numerical results show good agreement with experimental measurements and the theoretical double-multiple-streamtube model. Turbine sensitivity to parametric variations was also demonstrated in the full-scale numerical study. This work concludes that the developed model can effectively predict hydrodynamic performance and structural design blade loads of a vertical-axis marine current turbine.
Ground energy systems: delivering the potential
Authors: Preene M. , Powrie W.
Published: April 2009

Ground energy systems are increasingly being considered as an alternative to traditional heating and cooling systems as a way to reduce carbon emissions, control energy costs and improve the environmental performance of buildings. These systems use the ground and groundwater beneath a site as a heat source or sink, interacting through boreholes or pipes that exchange heat with the ground. This paper reviews the principles underpinning the systems and describes the two main types of system (open loop and closed loop). Four potential barriers to wider scale application of ground energy systems are highlighted. These are thermal interference between neighbouring systems in densely developed urban areas, increasing environmental regulation of below-ground elements, capital cost and the need to ensure that systems are sustainable in the long term. If the full potential of ground energy systems is to be realised, it is important that input from geotechnical and geological specialists is used to ensure that the below-ground elements are designed using appropriate design tools and site-specific data. It is also important that appropriate post-occupancy monitoring is in place to provide feedback to designers on the long-term performance of these systems.
Wetland system for primary treatment of landfill leachate
Authors: Fannin C. A. , Spraggs R. E. , Danes P. , Mortimer R. J. G.
Published: April 2009

A proprietary constructed wetland system has been developed as a long-term sustainable alternative for the treatment of high-nitrogen effluents such as landfill leachates. The system design is an enhancement of the microbiological processes that occur naturally in salt-marsh systems and extends the process capability of traditional vertical-flow constructed wetlands. Performance monitoring has demonstrated treatment rates of 69–95% per cell from a methanogenic landfill leachate influent containing 1400 mg/l ammoniacal-nitrogen at both pilot and laboratory scale. Two systems are currently being commissioned in the UK and applications for a further two systems are being considered by the UK Environment Agency.
Doing “Good” With Limited Resources: Is It Good Enough in the Provision of Quality Clinical Care?
Authors: Ulrich Connie M. , Grady Christine
Published: April 2009

The article discusses the ethical challenges advanced practitioners face in the provision of quality clinical care. According to the authors, nurses and physicians are trying to balance their clinical judgment of what patients need with the cost control measures of health plans. But even when the provider does the best he or she can, it may not feel good enough. To benefit patients and the profession, advanced practitioners need to be part of the conversations that reign in costs and shape sound health care policies.
Practice Value and Worth of a DNP
Authors: Mackey Thomas A.
Published: April 2009

The worth and value of a doctorally prepared nurse practitioner (DNP) or distinct and frequently misunderstood concepts. While worth refers to dollars generated, value refers to dollars plus intangibles, such as quality, savings, and good will, generated by the DNP. The following article discusses the two concepts and provides pointed examples for the DNP to apply in a practice setting.
Sub-grain boundary mobilities during recovery of binary Al–Mn alloys
Authors: Barou Fabrice , Maurice Claire , Feppon Jean-Marie , Driver Julian
Published: April 2009

The influence of Mn solute atoms on sub-grain boundary mobilities in Al has been determined by accurate electron backscatter diffraction analysis of the sub-grain sizes and misorientations during recovery annealing. High purity Al-0.1 and 0.3 wt.% Mn alloys were deformed by plane strain compression at room temperature to equivalent strains of 1.8 and annealed in the temperature range 150 – 300 °C. An original method of image analysis on sub-boundaries from electron backscatter diffraction maps was applied to quantify the sub-grain size distributions. The change in average sub-grain size with time at several temperatures was then used to estimate sub-grain boundary mobilities in both Al – Mn alloys. The activation energies for sub-grain mobility were found to be 48 and 52 and kJ mol– 1 for the 0.1 and 0.3 % Mn alloys respectively, with the higher Mn alloy exhibiting lower rates. The sub-boundary mobilities are higher than expected from previous similar work on deformed Al – Si crystals. The orientation dependence of sub-grain growth is also examined.
Second-order faceting–roughening of the tilt grain boundary in zinc
Authors: Straumal Boris B. , Gornakova Alena S. , Sursaeva Vera G. , Yashnikov Viktor P.
Published: April 2009

The faceting of the almost stationary tilt grain boundary with a misorientation angle of 84° in the Zn bicrystal has been investigated. The shape of the very slow migrating grain boundary has been studied in situ between 350 and 400 °C using polarized light. Two intersecting facets lie in the closely-packed planes of the constrained coincidence sites lattice with coincidence parameter = 15. In the as-grown sample flat grain boundary facets form the sharp first-order ridge with the break of the first derivative y/x of the grain boundary shape similar to those observed in our previous works on GB faceting in Zn. However, above 350 °C the sharp first-order ridge is substituted by the smooth grain boundary portion without a ∂y/∂xderivative break similar to that observed in twin grain boundaries in Mo. The transformation of the as-grown first-order grain boundary ridge into continuous one has been observed for the first time. The critical parameter α has been calculated using the grain boundary shape in the transition region. α increases from α = 1.7 ± 0.07 for 350 °C to α = 1.9 ± 0.07 for 385 °C approaching the α = 2 value predicted in the mean-field Andreev model for the continuous surface roughening.
The combined effect of static recrystallization and twinning on texture in magnesium alloys AM30 and AZ31
Authors: Martin Étienne , Jiang Lan , Godet Stéphane , Jonas John J.
Published: April 2009

The potential for decreasing the texture intensity generated during the bulk deformation of Mg alloys was investigated using a combination of contraction twinning, double (secondary) twinning and static recrystallization. A large number of twins was induced by tensile deformation at room temperature. Their volume fraction and the variants selected during straining were found to be largely responsible for the changes evident in the deformation texture. Recrystallization of the twins generated a fine-grained microstructure, although no growth into the matrix grains was observed. In this way, annealing of the deformed samples did not lead to significant further texture changes.
Control of recrystallisation texture and texture-related properties in industrial production of aluminium sheet
Authors: Engler Olaf , Hirsch Jürgen
Published: April 2009

The principles of recrystallisation texture formation upon hot rolling and annealing of industrial aluminium alloy sheets are presented. It is demonstrated how texture control is applied during industrial processing of aluminium sheet so as to improve texture-related properties. This is illustrated by way of several examples, covering high-purity aluminium sheet for electrolytic capacitors, AlMnMg alloys for packaging and AlMgSi alloys for car body applications.
Early detection of crack initiation sites in TiAl alloys during low-cycle fatigue at high temperatures utilizing digital image correlation
Authors: Niendorf Thomas , Burs Christian , Canadinc Demircan , Maier Hans J.
Published: April 2009

Fatigue-induced damage accumulation was investigated in a third generation titanium aluminide alloy both at room temperature and at a temperature of 700 °C promoting oxidation. The digital image correlation technique was utilized for monitoring the evolution of local strain fields with cyclic deformation at both temperatures. With the aid of a newly adopted surface patterning technique, digital image correlation successfully detected the crack initiation sites prior to the actual formation of the cracks. Despite the oxidation at elevated temperatures, digital image correlation could detect the crack initiation sites at the early stages of the cyclic deformation, laying out the potential of this technique for monitoring the damage evolution in various metallic materials under severe service conditions.
On the solute-defect interaction in the framework of a defactant concept
Authors: Kirchheim Reiner
Published: April 2009

It will be shown that there is an analogy between surfactants in liquids which stabilize structures with large surface areas such as foams or microemulsions, and certain components in a crystalline solid, which stabilize defects such as grain boundaries and dislocations. These components are then called defactants. In the presence of defactants microstructural changes may occur because some of the defects compete more successfully for segregation of the defactants than others. Thus voids are formed at grain boundaries of Cu – Bi alloys because the formation energy of voids is provided by the interaction energy of Bi-atoms of the newly created surface. Or the beneficial role of rhenium on the high temperature creep of superalloys may be interpreted as a deficiency of defactants stabilizing dislocations and/or vacancies. These examples are discussed in the present work after a general treatment of the role of defactants.
Superplastic failure mode in ultrafine grained magnesium alloy AZ31
Authors: Lapovok Rimma , Williams Tim , Estrin Yuri
Published: April 2009

The paper addresses the failure mode of ultrafine grained magnesium alloy AZ31 under superplastic deformation conditions. The ultrafine grain structure and the resulting exceptional superplastic properties were produced by Equal Channel Angular Pressing with an imposed hydrostatic pressure conducted at a relatively low temperature of 150 °C. The mechanism of the superplastic ductility was studied by examining the fracture surfaces and internal cavities in superplastically deformed specimens by scanning electron microscopy. The presence of Mg17Al12 particles was identified as the controlling microstructural feature giving rise to porosity formation and limiting tensile ductility. Fine details of the failure process depending on the particle and precipitate structure as well as textural effects were described.
A model of grain boundary diffusion in polycrystals with evolving microstructure
Authors: Klinger Leonid , Rabkin Eugen
Published: April 2009

We consider grain boundary diffusion in a polycrystal in which normal grain growth occurs simultaneously with diffusion. We assume that any point within the diffusion zone is swept a number of times by migrating grain boundaries, and develop a model which operates with the average concentrations of the diffusant in the planes parallel to diffusion front. We derive analytical expressions describing the diffusion profiles both for constant source and instantaneous source boundary conditions. Finally, we suggest a practical method for extracting the grain boundary diffusion coefficient from experimentally measured diffusion profiles. This method relies on microstructure characterization and requires the grain growth constant and grain growth exponent to be determined in the independent set of experiments.
Comparison of texture evolution in fcc metals predicted by various grain cluster homogenization schemes
Authors: Eisenlohr Philip , Tjahjanto Denny D. , Hochrainer Thomas , Roters Franz , Raabe Dierk
Published: April 2009

We introduce a new material point homogenization scheme – the ‘Relaxed Grain Cluster’ (RGC) – based on a cluster of grains and formulated in the framework of finite deformations. Two variants of this scheme, which allow for different degrees of relaxation, are compared to two variants derived from the infinitesimal-strain grain interaction model regarding the evolution of texture predicted for plane-strain compression of a commercial aluminum alloy. The RGC schemes give the closest match to experimental reference on both the -fiber and the -skeleton line. The intensity of the brass texture component is found to be rather sensitive to the homogenization scheme. However, the observed decrease in texture intensity as a function of the homogenization scheme for the Cu and S component on the -skeleton line can be correlated to the number of degrees of freedom in the cluster which are left unconstrained by the respective scheme. This is in line with the significant dependence of the Cu and S component intensity on boundary conditions reported in earlier studies.
Nanoindentation of Ti50Ni48Fe2 and Ti50Ni40Cu10 shape memory alloys
Authors: Zheng Hongxing , Pfetzing Janine , Frenzel Jan , Eggeler Gunther
Published: April 2009

In the present paper we use nanoindentation to investigate two shape memory alloys, austenitic Ti50Ni48Fe2 and martensitic Ti50Ni40Cu10 which both show two step martensitic transformations on cooling from the high temperature regime. No such two step features were observed during nanoindentation. Load controlled nanoindentation experiments were performed using a Berkovich indenter using maximum loads ranging from 0.5 to 85 mN resulting in maximum indentation depths between 30 and 1350 nm. For small maximum indentation loads below 5 mN, longer indentation times result in larger indentation depths (austenitic Ti50Ni48Fe2). At loads of about 1 mN the indentation curves show an abrupt change in slope which we suggest to be related to an interaction of the deformation and failure of a thin oxide layer and the formation of stress induced martensite (austenitic Ti50Ni48Fe2) or the de-twinning of martensite (martensitic Ti50Ni40Cu10). Nanohardnesses and shape recovery ratios strongly increase with decreasing indentation depths below 400 nm. For larger indentation depths, constant values are observed (austenitic Ti50Ni48Fe2: nanohardness 2.45 GPa/recovery ratio 0.25, martensitic Ti50Ni40Cu10: nanohardness 1.6 GPa/recovery ratio 0.4).
Testing a curvature driven moving finite element grain growth model with the generalized three dimensional von Neumann relation
Authors: Uyar Fatma , Wilson Seth R. , Gruber Jason , Lee Sukbin , Sintay Stephen , Rollett Anthony D. , Srolovitz David J.
Published: April 2009

The von Neumann – Mullins relation has been extended to higher dimensions by MacPherson and Srolovitz. Their exact solution relates the rate of volume change of an individual grain in a 3-dimensional isotropic polycrystal to its mean width and total length of triple lines (assuming isotropic boundaries). The objective of this study is to verify that grains in a moving finite element grain growth model obey this law. Algorithms have been developed in order to calculate mean width of individual grains in digital microstructures for which the grain structure is discretized with both volumetric and surface meshes. Theoretical rate predictions were obtained from the measured mean widths and triple line lengths. Good agreement was found between growth rates measured in the simulations and the predictions of MacPherson – Srolovitz theory for the cases of an isolated shrinking sphere, individual grains in a digitally generated coarse polycrystal, and individual grains in a microstructure reconstructed from serial sectioning of stabilized cubic zirconia. Departures from this relationship appeared to be related to the grain shape.
Interface Migration in Metals (IMM):“Vingt Ans Après” (Twenty Years Later)
Authors: Molodov D. A. , Shvindlerman L. S.
Published: April 2009

The paper represents a comprehensive although rather brief overview of the scientific activity of the Institute of Physical Metallurgy and Metal Physics (IMM), RWTH Aachen University, in the field of grain boundary physics for the past twenty years under the leadership of Professor Günter Gottstein.
The Optimal Operation Criteria for a Gas Turbine Cogeneration System
Authors: Ishida Yasushi , Bannai Masaaki , Miyazaki Takahiko , Harada Yasushi , Yokoyama Ryuichi , Akisawa Atsushi
Published: April 2009

The study demonstrated the optimal operation criteria of a gas turbine cogeneration system based on the analytical solution of a linear programming model. The optimal operation criteria gave the combination of equipment to supply electricity and steam with the minimum energy cost using the energy prices and the performance of equipment. By the comparison with a detailed optimization result of an existing cogeneration plant, it was shown that the optimal operation criteria successfully provided a direction for the system operation under the condition where the electric power output of the gas turbine was less than the capacity
Closing the Global Energy and Nutrient Cycles through Application of Biogas Residue to Agricultural Land – Potential Benefits and Drawback
Authors: Arthurson Veronica
Published: April 2009

Anaerobic digestion is an optimal way to treat organic waste matter, resulting in biogas and residue. Utilization of the residue as a crop fertilizer should enhance crop yield and soil fertility, promoting closure of the global energy and nutrient cycles. Consequently, the requirement for production of inorganic fertilizers will decrease, in turn saving significant amounts of energy, reducing greenhouse gas emissions to the atmosphere, and indirectly leading to global economic benefits. However, application of this residue to agricultural land requires careful monitoring to detect amendments in soil quality at the early stages.
Biodegradable Cellulose-based Hydrogels: Design and Applications
Authors: Sannino Alessandro , Demitri Christian , Madaghiele Marta
Published: April 2009

Hydrogels are macromolecular networks able to absorb and release water solutions in a reversible manner, in response to specific environmental stimuli. Such stimuli-sensitive behaviour makes hydrogels appealing for the design of ‘smart’ devices, applicable in a variety of technological fields. In particular, in cases where either ecological or biocompatibility issues are concerned, the biodegradability of the hydrogel network, together with the control of the degradation rate, may provide additional value to the developed device. This review surveys the design and the applications of cellulose-based hydrogels, which are extensively investigated due to the large availability of cellulose in nature, the intrinsic degradability of cellulose and the smart behaviour displayed by some cellulose derivatives.
Methanetrisulfonic Acid: A Highly Efficient Strongly Acidic Catalyst for Wagner-Meerwein Rearrangement, Friedel-Crafts Alkylation and Acylation Reactions. Examples from Vitamin E Synthesis
Authors: Bonrath Werner , Aquino Fabrice , Haas Alois , Hoppmann Simone , Netscher Thomas , Pace Francesco , Pauling Horst
Published: April 2009

Methanetrisulfonic acid had been prepared for the first time over 140 years ago, but it was used only scarcely in chemical transformations. In the course of our activities dealing with key-steps of industrial syntheses of vitamins, e.g. economically important vitamin E (acetate), we found that methanetrisulfonic acid is an extremely effective catalyst in a variety of reactions. Examples of its applications are Wagner-Meerwein rearrangements, Friedel-Crafts alkylations and ring closures, as well as acylation reactions. Use of this catalyst in truly catalytic amounts (0.04-1.0 mol%) resulted in highly selective transformations and yields over 95%. (Remark by the authors: We are describing only one example each for the various types of reactions. Therefore, it would be more appropriate to write (here and in the Introduction and in the Conclusion sections): “Wagner-Meerwein rearrangement, Friedel-Crafts alkylation and ring closure, as well as acylation reactions”)
Frequency, Risk, and Cost of Gout-related Episodes Among the Elderly: Does Serum Uric Acid Level Matter?
Authors: WU ERIC Q. , PATEL PANKAJ A. , MODY REEMA R. , YU ANDREW P. , CAHILL KEVIN E. , TANG JACKSON , KRISHNAN ESWAR
Published: April 2009

Objective.

We examined the association between serum uric acid (SUA) level and the frequency, risk, and cost of gout flares among the elderly.

Methods.

Data were extracted from the Integrated Healthcare Information Services claims database (1999–2005). Patients were included if they had gout, were aged 65 years and older and had both medical and pharmacy benefits, and electronic laboratory data. Patients with gout and gouty episodes were identified using algorithms based on ICD-9-CM codes and medications. Logistic regression and negative binomial regressions were used to study the relationship between SUA concentration and the annual frequency and one-year risk of gout episodes. Generalized linear models were used to examine the direct healthcare costs associated with gout episodes in the 30 days following each episode.

Results.

Elderly patients with gout (n = 2237) with high (6–8.99 mg/dl) and very high (> 9 mg/dl) SUA concentrations were more likely to develop a flare within 12 months compared to patients with normal (< 6 mg/dl) SUA levels (OR 2.1, 95% CI 1.7–2.6; OR 3.4, 95% CI 2.6–4.4, respectively). In multivariate regressions, the average annual number of flares increased by 11.9% (p < 0.001) with each unit-increase in SUA level above 6 mg/dl (p < 0.001). Among patients with very high SUA levels, average adjusted total healthcare and gout-related costs per episode were $2,555 and $356 higher, respectively, than those of patients with normal SUA levels (both p < 0.001).

Conclusion.

Higher SUA levels are associated with increased frequency and risk of gout episode, and with higher total and gout-related direct healthcare costs per episode.
Contrast-enhanced Coded Phase-inversion Harmonic Sonography of Knee Synovitis Correlates with Histological Vessel Density: 2 Automated Digital Quantifications
Authors: KAISER MARIE-JOËLLE , HAUZEUR JEAN-PHILIPPE , BLACHER SILVIA , FOIDART JEAN-MICHEL , DEPREZ MANUEL , ROSSKNECHT ALEXANDRA , MALAISE MICHEL G.
Published: April 2009

Objective.

To use contrast-enhanced coded phase-inversion harmonic B-mode sonography to assess the acoustic enhancement of the synovial area of the knee; and to compare the data with the histological vessel density.

Methods.

Eleven patients eligible for a knee arthroscopy were studied. Acoustic quantification was carried out by a digital image analysis program that detects the time-dependent increase [intensity (time) = k × time + C] of gray-level intensity in all the pixels of a specific region of interest (ROI) following intravenous injection of the microbubble contrast agent sulfur hexafluoride. Echo-guided synovial biopsies were carried out in the same ROI. Synovial vessel areas were quantified after Factor VIII immunostaining of synovial biopsies using an automated digital image analysis.

Results.

Significant (p < 0.05) correlations were observed between histological vessel density and percentage of the synovial area with a k value > 0.01 (r = 0.93) and kmaxvalues (r = 0.79), as well as between the 2 latter parameters (r = 0.72). The histological vessel density and the 2 acoustic parameters were also significantly correlated with the logarithm of erythrocyte sedimentation rate (r = 0.77, r = 0.87, r = 0.67, respectively) and with log C-reactive protein serum concentration (r = 0.69, r = 0.83, r = 0.62, respectively).

Conclusion.

Contrast-enhanced coded phase-inversion harmonic B-mode sonography coupled with an appropriate data analysis method is a new tool to identify and quantify vessel density in knee synovitis.
Utilization Trends of Tumor Necrosis Factor Inhibitors Among Patients with Rheumatoid Arthritis in a United States Observational Cohort Study
Authors: LEE SUSAN J. , CHANG HONG , YAZICI YUSUF , GREENBERG JEFFREY D. , KREMER JOEL M. , KAVANAUGH ARTHUR
Published: April 2009

Objective.

Studies have suggested that early institution of tumor necrosis factor (TNF) inhibitors improves functional status and slows radiographic progression among patients with rheumatoid arthritis (RA). To determine whether these findings have altered practice patterns, we used the Consortium of Rheumatology Researchers of North America (CORRONA) registry to assess the pattern of TNF inhibitor utilization in the US over time.

Methods.

Demographics and disease activity data were collected for patients with RA. The trend of TNF inhibitor use during 2002–06 was evaluated prospectively using linear and logistic regression models.

Results.

Of the 11,397 patients with RA, 66% and 34% had established RA and early RA (disease duration < 3 yrs), respectively. The majority of patients were female and Caucasian. Despite comparable levels of disease activity, more of the patients with established RA were taking TNF inhibitors than those with early RA (40% vs 25%; p < 0.0001). The majority of patients (70%) taking TNF inhibitors were also receiving disease modifying antirheumatic drugs. The use of TNF inhibitors increased at a rate of 2.8% per year in established RA and 1.2% per year in early RA. The mean Clinical Disease Activity Index at the start of TNF inhibitors decreased at a rate of −0.233 per quarter (p = 0.006), while the mean Disease Activity Score decreased at a rate of −0.04 per quarter (p = 0.022).

Conclusion.

Utilization of TNF inhibitors in this multicenter, observational US cohort is increasing in both early and established RA, although it is more prominent among patients with established RA. The level of disease activity at which TNF inhibitors were initiated decreased over time in patients with both established and early RA.
Conventional Lipid Profile and Lipoprotein(a) Concentrations in Treated Patients with Rheumatoid Arthritis
Authors: GARCÍA-GÓMEZ CARMEN , NOLLA JOAN M. , VALVERDE JOSEP , GÓMEZ-GERIQUE JUAN A. , CASTRO MARÍA J. , PINTÓ XAVIER
Published: April 2009

Objective.

Patients with rheumatoid arthritis (RA) have an increased cardiovascular risk not completely explained by traditional cardiovascular risk factors. If the proatherogenic lipid profile observed in active and untreated RA improves by effectively treating RA without the use of a lipid-lowering agent, other nonconventional cardiovascular lipid risk factors may be implicated. We evaluated conventional lipid risk factors and lipoprotein(a) in treated patients with RA.

Methods.

This cross-sectional study was conducted in 122 patients with RA. Lipid profiles of patients were compared with a control group, consisting of a population-based study cohort (DRECE study), matched for sex, age, menopausal status, and body mass index. Excess lipoprotein(a) was defined by a serum concentration > 0.3 g/l.

Results.

High-density lipoprotein cholesterol (HDL-c) concentrations were higher in pre- and postmenopausal women with RA than in controls (p = 0.023 and p ≤ 0.001, respectively). All RA patients had significantly lower levels of apolipoprotein B and apolipoprotein B/apolipoprotein A-I ratio, and postmenopausal women with RA also had significantly lower low-density lipoprotein cholesterol and total cholesterol levels than their respective controls. No differences were observed in serum levels of apolipoprotein A-I and triglyceride. All RA patients had higher lipoprotein(a) values than controls. Fourteen men (56%) and 10 (53%) and 42 (54%) pre- and postmenopausal women with RA, respectively, had hyperlipoproteinemia(a).

Conclusion.

RA patients undergoing antirheumatic therapy display a nonatherogenic conventional lipid profile, i.e., high HDL-c, low apolipoprotein B concentrations, and low apolipoprotein B/apolipoprotein A-I ratio. This may be counteracted by the high prevalence of hyperlipoproteinemia(a) observed in these patients.
Serum Urate During Acute Gout
Authors: SCHLESINGER NAOMI , NORQUIST JOSEPHINE M. , WATSON DOUGLAS J.
Published: April 2009

Objective.

To study the frequency of normal serum urate (SU) levels during acute gout in the largest studies of acute gout treatment to date.

Methods.

Data collected from 2 randomized controlled clinical trials assessing the efficacy of etoricoxib or indomethacin for 7 days in acute gout were used to assess SU levels during acute gouty attacks. Efficacy was similar with both agents, so both groups were combined for analysis.

Results.

A total of 339 patients were enrolled in the 2 studies; 94% were male; mean age was 50.5 years. At baseline, 14% of patients had a “true” normal SU (≤ 6 mg/dl) and 32% had SU ≤ 8 mg/dl during acute gout. Baseline mean SU was 7.1 versus 8.5 mg/dl (p < 0.001) in those taking allopurinol versus nonusers. Patients taking chronic allopurinol were more likely to have lower SU at baseline compared to those not taking chronic allopurinol (p < 0.001) during the acute attack.

Conclusion.

A normal SU level at presentation does not exclude an acute gouty attack. In the largest studies of acute gout to date, attacks still occurred despite SU levels being below 6.8 mg/dl, the saturation level for urate. This may be attributed to persistence of tophi and an increased body uric acid pool. Additional studies are needed to determine the correlation between SU and the body uric acid pool as well as the relationship to timing of changes during acute gout.
Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage: Clinical Associations in Obese Adults
Authors: ANANDACOOMARASAMY ANANTHILA , GIUFFRE BRUNO M. , LEIBMAN STEVEN , CATERSON IAN D. , SMITH GARETT S. , FRANSEN MARLENE , SAMBROOK PHILIP N. , MARCH LYN M.
Published: April 2009

Objective.

Delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) is used to assess cartilage glycosaminoglycan distribution. Our aim was to determine the relationships between self-reported pain and disability, clinical variables, and serum leptin, and dGEMRIC indices in obese subjects with and without clinical knee osteoarthritis (OA).

Methods.

Seventy-seven subjects were recruited from laparoscopic adjustable gastric banding or exercise and diet-weight loss programs. The dGEMRIC index was assessed on MRI according to established protocol. Regression analysis adjusted for age, sex, body mass index (BMI), and presence of clinical knee OA.

Results.

Mean age and BMI were 51 ± 12.7 years and 39.6 ± 6.2 kg/m2. Twenty-three subjects (30%) had clinical knee OA (American College of Rheumatology criteria). The medial and lateral dGEMRIC indices were 538 ± 80 ms and 539 ± 86 ms. Age correlated negatively with medial (r = −0.40, p < 0.001) and lateral (r = −0.29, p = 0.012) dGEMRIC index. Subjects with clinical knee OA had significantly lower medial dGEMRIC index; however, no association was found for BMI. Varus alignment correlated with lower medial dGEMRIC index (r = −0.43, p < 0.006), while quadriceps strength correlated positively with lateral dGEMRIC index (r = 0.32, p = 0.008). There was also a negative correlation between serum leptin and lateral dGEMRIC index in women (r = −0.39, p = 0.035), with a trend in men (r = −0.52, p = 0.08). There were weak associations with physical disability, as self-reported on the WOMAC questionnaire.

Conclusion.

In obese subjects, knee dGEMRIC index was associated with age, clinical knee OA, abnormal tibiofemoral alignment, and quadriceps strength. Longitudinal studies are required to assess the potential for improvement in dGEMRIC index with interventions such as strength training.
Spondyloarthritis Is Associated with Poor Function and Physical Health-Related Quality of Life
Authors: SINGH JASVINDER A. , STRAND VIBEKE
Published: April 2009

Objective.

To study physical function and health-related quality of life (HRQOL) in US veterans with spondyloarthritis (SpA).

Methods.

In a postal survey of 70,334 eligible veterans, demographics, performance of activities of daily living (ADL), and HRQOL, by Veterans Short Form-36, were queried; 58% responded (n = 40,508). Databases providedInternational Classification of Diseases, 9th ed. codes for ankylosing spondylitis (AS), psoriatic (PsA) and reactive arthritis (ReA), comorbidities, and demographics. Multivariable linear/logistic regressions compared ADL limitations and HRQOL in SpA versus non-SpA, and predictors in SpA.

Results.

Six hundred sixty-four veteran respondents had diagnoses of SpA: AS, n = 100; PsA, n = 551; ReA, n = 13. Veterans with AS, PsA, and ReA had significantly more limitations in dressing (44%, 23%, 24% vs 22%; p = 0.0002), transferring (57%, 42%, 64% vs 39%; p = 0.0006), walking (74%, 57%, 67% vs 54%; p = 0.0005), and overall mean ADL limitations (2.5, 1.7, 2.1 vs 1.6; p < 0.0001) compared to veterans without SpA, after multivariable adjustment. Limitations in each ADL in patients with SpA were 1.3–5.3 times that of an age-matched US cohort. Physical HRQOL was significantly lower compared with non-SpA veterans (p < 0.0001 for physical component summary, physical functioning, role physical, and bodily pain; p = 0.004 for general health) and age-sex-matched US norms; all differences exceeded clinically meaningful threshold of 5–10 units. More limitations in ADL were significantly associated with lower physical component summary scores in patients with AS and with lower physical and mental component summary scores in PsA.

Conclusion.

After adjustment for differences in demographics and comorbidities, poorer physical function and HRQOL were observed in patients with SpA. Strategies focused to improve/maintain functional status are important for treatment of SpA.
Less Radiographic Progression with Adalimumab Plus Methotrexate Versus Methotrexate Monotherapy Across the Spectrum of Clinical Response in Early Rheumatoid Arthritis
Authors: EMERY PAUL , GENOVESE MARK C. , van VOLLENHOVEN RONALD , SHARP JOHN T. , PATRA KAUSHIK , SASSO ERIC H.
Published: April 2009

Objective.

To determine the relationship between radiographic progression and clinical response for adalimumab plus methotrexate (MTX) versus either monotherapy in patients with early rheumatoid arthritis (RA) in the PREMIER study.

Methods.

Patients with early RA who received adalimumab plus MTX (n = 240), adalimumab (n = 222), or MTX (n = 216) were grouped by American College of Rheumatology (ACR) response, 28-joint Disease Activity Score (DAS28), or remission-like state [tender joint count (TJC) = 0; DAS28 < 2.6; swollen joint count = 0; ACR100] at 26 and 104 weeks. Radiographic progression was assessed by cumulative probability plots, mean changes in total Sharp score (ΔTSS), and percentages of progressors (ΔTSS > 0.5).

Results.

Across the spectrum of clinical outcomes, including ACR20 nonresponses and remission-like responses, therapy with adalimumab plus MTX permitted less radiographic progression at Weeks 26 and 104 than MTX monotherapy. Adalimumab monotherapy was generally intermediate. A strong, proportional relationship was observed between clinical response and radiographic efficacy only for MTX monotherapy. The monotherapies approximated the radiographic efficacy of adalimumab plus MTX only among remission-like responders, although progression was significantly greater with MTX monotherapy versus adalimumab plus MTX for patients with TJC = 0. Concurrent clinical (DAS28 < 2.6) and radiographic (ΔTSS ≤ 0.5) remission was significantly more frequent at Week 104 with adalimumab plus MTX (45%) than with adalimumab (25%) or MTX (18%) monotherapy.

Conclusion.

In patients with early RA, adalimumab plus MTX resulted in less radiographic progression than MTX monotherapy across the spectrum of clinical response, including ACR20 non-responses and remission-like responses.