bluuebunny/crossref_metadata_2025 huggingface dataset:
Update: Acute Otitis Media
Authors: Shaikh Nader , Hoberman Alejandro
Published: February 2010

CME EDUCATIONAL OBJECTIVES

1.

Review the recent changes in the microbiology of acute otitis media.

2.

Differentiate the physical exam findings characteristic of acute otitis media (AOM) from those of otitis media with effusion (OME).

3.

Discuss the evidence to support antimicrobial management of AOM in children.
Displacement Chromatography of Proteins
Authors: McAtee C. Patrick
Published: February 2010

This unit discusses the important parameters in designing and optimizing a separation by ion‐exchange displacement chromatography, including preparing the sample and choosing a matrix, column, and buffer. Protocols are provided for testing a column, determining binding and elution conditions, displacing the sample, and cleaning, regenerating, and storing of displacement columns. Curr. Protoc. Protein Sci. 59:8.9.1‐8.9.14. © 2010 by John Wiley & Sons, Inc.
Rapid Detergent Removal from Peptide Samples with Ethyl Acetate for Mass Spectrometry Analysis
Authors: Yeung Yee‐Guide , Stanley E. Richard
Published: February 2010

Detergents are required for the extraction of hydrophobic proteins and for the maintenance of their solubility in solution. However, the presence of detergents in the peptide samples severely suppresses ionization in mass spectrometry (MS) analysis and decreases chromatographic resolution in LC‐MS. Thus, detergents must be removed for sensitive detection of peptides by MS. This unit describes a rapid protocol in which ethyl acetate extraction is used to remove octylglucoside from protease digests without loss of peptides. This procedure can also be used to reduce interference by sodium dodecyl sulfate, Nonidet P‐40, or Triton X‐100 in peptide samples for MS analysis. Curr. Protoc. Protein Sci. 59:16.12.1‐16.12.5. © 2010 by John Wiley & Sons, Inc.
Prevention and Protection: Threats and Challenges From A Homeland Defense Perspective
Authors: McManus Jeffrey D.
Published: February 2010

President Bush signed and released the
National Strategy for Homeland Security
in July 2002. This strategy highlighted the new threat environment, discussed our national vulnerabilities, and outlined critical mission areas necessary to meet the new security challenge. While the strategy outlined threats, that is incidents intentionally instigated by an adversary to cause loss or damage, it did not adequately address nonhostile hazards. Events such as accidents or natural disasters can also result in catastrophic damage and must be considered for comprehensive risk management. The strategy also did not differentiate between true mission areas (i.e.
what
we need to do), the domain environment (i.e.
where
we need to do them), and the preparedness continuum (i.e.
when
we need to do them). To be fair, the strategy does discuss protection and response activities. However, it does not fully articulate the steady‐state prevention functions that can be implemented preincident to minimize general risks. This paper will outline the categories of threats and hazards that should be considered, and highlight the preparedness continuum, focusing on the proactive activities, and challenges faced in the pre‐event functions of prevention and protection.
Transportation Security Roles and Responsibilities
Authors: Western Jeffrey L. , Contestabile John , Englot Joseph M.
Published: February 2010

In the event of a man‐made incident or natural disaster it is apparent the interconnectivity and the ripple economic impacts of a transportation system require coordinated solutions and jurisdictional coordination beyond the current silo level in protecting our nation's
critical infrastructure and key resources
(CIKR). This paper will provide guidance on the roles and responsibilities of ensuring the nation's transportation security, not only at the public sector level but also at the private sector and the general population levels.
Data Sources for Biosurveillance
Authors: Walters Ronald A. , Harlan Pete A. , Nelson Noele P. , Hartley David M.
Published: February 2010

Biosurveillance requires a synthesis of analytic approaches derived from the natural disaster, public health, medical, meteorological, and social science communities, among others, and it is the cornerstone of early disease detection. Biosurveillance includes the analyses of timely data, often fusing time series of many different types of data, to infer the status of public health rather than solely exploiting data having diagnostic specificity. This paper summarizes major systems dedicated to such an endeavor with emphasis on those that use formal reporting sources and those that use open source collection. Although, individual systems have different missions and approaches, there are many complementarities among them that if creatively exploited could be the basis of an effective global biosuveillance enterprise.
Critical Infrastructures at Risk: A European Perspective
Authors: Gheorghe Adrian V. , Masera Marcelo
Published: February 2010

Infrastructures such as energy, water supply, and telecommunication, are so vital, critical and ubiquitous that their incapacity or destruction would affect the security and the social welfare of any nation. Modern infrastructures cope with new types of emerging risks, due to a variety of threats/hazards such as natural disasters, malicious attacks, technical failures etc. Factors that have transformed the way how infrastructures are designed, developed, operated and de‐commissioned relate to liberalization of markets. the interdependency among infrastructures, the increase of cross‐border interconnections, changes in ICT, the manifestation of systemic risks.

The present paper addresses an European view of critical infrastructures development by adopting risks and vulnerabilities performance within an all hazard approach practical construct. The presentation and the risk assessment landscape are fully articulated within the current legislative framework established by the European Commission and other appropriate legislative bodies.

New entities such as European Critical Infrastructures (ECI) are described and documented in view of their protection. A number of principles are highlighted such as subsidiarity, complementary, confidentiality, stakeholder cooperation, proportionality, the advent of the concept of system of systems.

A detailed investigation in view of the evolution of risk is made for Critical Electricity Infrastructures. A number of current trends such as the liberalization of the European electricity sector, the internationalization of the electricity system (e.g. interconnection among national grids), evolutionary unsuitability (i.e. current transmission networks are used in ways for which they were not initially designed), and the ubiquity of ICS are highlighted and investigated. The authors argue that i) the amalgamation of electric power systems and ICT produces a new construct, “Electricity plus Information” (E+I), ii) there is a need for risk governance, science and technology in order to cope with new complex situations imposed upon us by the advent of SoS architectures, the involvement of a large variety of stakeholders.
CARVER
+Shock: Food Defense Software Tool
Authors: Pohl Phillip , Lindgren Eric , Williams Cecelia , Danneels Jeffrey , Browitt Robert , Eubanks Lee , Link Madison , Hunter Regina , Kautter Don , Woody Jon , Bryant Cory
Published: February 2010

The acronym CARVER represents the steps in a threat analysis exercise: Criticality, Accessibility, Recognizability, Vulnerability, Effect, and Recuperability. The CARVER+Shock software was developed as an easy‐to‐use tool for defending food production against malevolent attacks. Shock is added to incorporate the intangible focus of a terrorist in frightening a targeted group. The software uses the CARVER targeting methodology to identify components in a production process that are best suited for security improvements and recommends mitigative steps to improve defense. The food defense software is described and demonstrated on hypothetical yogurt and apple product food‐production processes. Two of the algorithms used to generate scores in the analysis are presented and the assumptions listed. The calculated scores are compared and discussed. Version 1.0 of the software is available free from the US Food and Drug Administration (FDA) website. Software upgrades for agriculture and for retail or restaurants analyses are being developed for release in 2009 along with Version 2.0.
Strategies for Protecting the Telecommunications Sector
Authors: Sullivant John
Published: February 2010

This article offers insight into the Telecommunications Sector's infrastructure and services and the importance of its survivability, to the economy and national security. It describes the interconnection between the Information Technology and Telecommunications infrastructures. It demonstrates the criticality of interdependency among other critical infrastructures and how their interconnection with the Information Technology and Telecommunications infrastructures is critical to their survivability. Specific vulnerabilities and challenges facing security planners as well as potential solutions for strengthening security weaknesses and advancing the continuity of telecommunications operations are discussed.
Economic Impact of a Livestock Attack
Authors: Hagerman Amy D. , McCarl Bruce A. , Mu Jianhong
Published: February 2010

This article describes the importance and challenges of modeling the economics of attacks to livestock agriculture through the introduction of an animal or zoonotic disease. The value of including economic evaluation is presented. The various types of economic impact categories needed to do a disease assessment are discussed, as well as what determines the severity of impacts in a particular situation. The article concludes with a short discussion of how to determine which economic loss categories to focus on, and the need for additional focus on key loss areas.
Disease severity and domain‐specific arthritis self‐efficacy: Relationships to pain and functioning in patients with rheumatoid arthritis
Authors: Somers Tamara J. , Shelby Rebecca A. , Keefe Francis J. , Godiwala Neha , Lumley Mark A. , Mosley‐Williams Angelia , Rice John R. , Caldwell David
Published: February 2010

Objective

To examine the degree to which disease severity and domains of self‐efficacy (pain, function, and other symptoms) explain pain and functioning in rheumatoid arthritis (RA) patients.

Methods

Patients (n = 263) completed the Arthritis Impact Measurement Scales 2 to assess pain and functioning (physical, affective, and social), the Arthritis Self‐Efficacy Scale to assess 3 self‐efficacy domains (pain, physical function, and other). Disease severity was assessed with C‐reactive protein level, physician's rating, and abnormal joint count. Structural equation modeling was used to examine 3 hypotheses: does disease severity have a direct relationship with pain and each area of functioning, does disease severity have a direct relationship with each arthritis self‐efficacy domain, and do the self‐efficacy domains mediate the relationship between disease severity and RA pain and each area of functioning.

Results

Disease severity was related to pain, physical functioning, and each self‐efficacy domain (β = 0.28–0.56, P < 0.001). Each self‐efficacy domain was related to its respective domain of functioning (e.g., self‐efficacy for pain was related to pain; β = 0.36–0.54, P < 0.001). Self‐efficacy mediated the relationship between disease severity and pain and functioning (β = 0.12–0.19, P < 0.001). Self‐efficacy for pain control and to perform functional tasks accounted for 32–42% of disease severity's total effect on their respective outcomes (e.g., self‐efficacy for pain control accounted for 32% of disease severity's total effect on pain). Variance accounted for by the total model was 52% for pain, 53% for physical functioning, and 44% for affective and social functioning.

Conclusion

Disease severity and self‐efficacy both impact RA functioning, and intervening in these areas may lead to better outcomes.
Rates and predictors of hydroxychloroquine retinal toxicity in patients with rheumatoid arthritis and systemic lupus erythematosus
Authors: Wolfe Frederick , Marmor Michael F.
Published: February 2010

Objective

Hydroxychloroquine (HCQ) retinopathy is of concern because of the potential seriousness of visual loss and the medicolegal consequences of failure to detect toxicity. However, there have been limited demographic data on which to base recommendations for screening. We have studied the largest unselected series of patients to date to evaluate the risk of toxicity and the relevance of purported risk factors.

Methods

We studied 3,995 patients with rheumatoid arthritis or systemic lupus erythematosus who had used HCQ, including 1,538 current users. We screened for self‐reported toxicity, and followed up on positive cases with detailed interviews and specialist confirmation. We categorized cases as “definite or probable” if there was bull's eye maculopathy or visual field loss.

Results

Of the lifetime users of HCQ, 6.5% discontinued therapy because of an eye problem, including 1.8% who reported HCQ retinal problems. However, definite or probable toxicity was documented in only 0.65% (95% confidence interval 0.31–0.93). The risk of toxicity was low in the initial 7 years of exposure, and was approximately 5 times greater after 7 years of usage (or 1,000 gm total exposure). Toxicity was unrelated to age, weight, or daily dosage. Eye examinations were obtained annually by 50.5% and every 6 months by 40.4% of patients.

Conclusion

HCQ toxicity remains uncommon, but increases markedly with the duration of therapy and exceeds 1% after 5–7 years. Toxicity was unassociated with age, daily dosage, or weight. These findings will aid the reformulation of screening guidelines.
Applying SEM‐Based X‐ray Microtomography to Observe Self‐Healing in Solvent Encapsulated Thermoplastic Materials
Authors: Mookhoek Steven D. , Mayo Sheridan C. , Hughes Anthony E. , Furman Scott A. , Fischer Hartmut R. , van der Zwaag Sybrand
Published: February 2010

In this work X‐ray microtomography was used to observe fracture and healing processes in a liquid‐based self‐healing thermoplastic material. The method was able to produce data of sufficient resolution (<10 μm) to observe ∼60 μm microcapsules containing solvent within a polymeric material and in particular their behavior around a crack zone after fracture and healing. The reconstructed data showed the distribution of filled and several empty microcapsules within the matrix material. Additional color segmentation and 3D rendering of the data unambiguously demonstrated a large concentration of ruptured microcapsules near the fracture surfaces, covering ∼75 μm span on both sides of the crack. A close investigation of the crack area confirmed the presence of healed and non‐healed regions. Further analysis of the segmented data allowed a quantitative determination of the release of the encapsulated solvent.
Photoperiod at conception predicts C677T‐MTHFR genotype: A novel gene‐environment interaction
Authors: Lucock Mark , Glanville Tracey , Ovadia Liz , Yates Zoë , Walker James , Simpson Nigel
Published: February 2010

Data is presented, which suggest that the day length a woman experiences during the periconceptional period predicts the C677T‐MTHFR genotype of her child. Logistic regression analysis involving 375 neonates born in the same geographical location within a three year period demonstrated that photoperiod (minutes) at conception predicts both genotype (P = 0.0139) and mutant allele carriage (P = 0.0161); the trend clearly showing that the 677T‐MTHFR allele frequency increases as photoperiod increases. We propose a number of explanations, including a hypothesis in which a long photoperiod around conception decreases maternal systemic folate because of UVA induced dermal oxidative degradation of 5‐methyl‐H4folate, leading to a lower cellular 5,10‐methylene‐H4folate status. In this scenario, 5,10‐methylene‐H4folate would be more efficiently used for dTMP and DNA synthesis by 677T‐MTHFR embryos than wildtype embryos giving the 677T‐MTHFR embryos increased viability, and hence increasing mutant T‐allele frequency. Alternate hypotheses include: increased seasonal availability of folate rich foods that genetically buffer any negative effect of 677T‐MTHFR in embryos; seasonal oxidative stress lowering embryo‐toxic homocysteine; an undefined hormonal effect of photoperiod on the neuroendocrine axis, which mediates genotype/embryo selection. The effect of photoperiod on genotype seems clear, but the speculative molecular mechanism underpinning the effect needs careful examination. Am. J. Hum. Biol., 2010. © 2010 Wiley‐Liss, Inc.
Offspring from endogamic vs. exogamic matings: Absence of anthropometric differences among Sardinian children (Italy)
Authors: Sanna E. , De Micco A. , Palmas L. , Soro M.R. , Vallascas E. , Danubio M.E.
Published: February 2010

This study evaluates possible differences in body dimensions among children from matings of different exogamy levels. The cross‐sectional sample consisted of 867 children, 435 males, and 432 females, 6–10 years old, attending elementary schools in the metropolitan area of Cagliari, the capital of Sardinia (Italy). The children were divided into two groups according to the level of exogamy. The first group consisted of children of parents born in the same Sardinian municipality and was considered endogamous sensu stricto. The second group included children of parents born in municipalities from different Sardinian linguistic domains and was considered exogamous. The Mann–Whitney test did not reveal significant differences between the two groups of children in the mean rank values of the 36 anthropometric variables considered, with the exception of cephalic circumference in males and chest depth in females. In particular, there were no significant differences for anthropometric variables considered to be indirect indicators of nutritional status: sum of skinfolds, waist/hip ratio, body mass index, total upper arm area, upper arm muscle area, and upper arm fat area. The results indicate that Sardinian children from marriages of different exogamy levels do not differ in body dimensions if they grow up with similar nutritional and socioeconomic conditions. Am. J. Hum. Biol., 2010. © 2010 Wiley‐Liss, Inc.
Dairy and milk consumption and child growth: Is BMI involved? An analysis of NHANES 1999–2004
Authors: Wiley Andrea S.
Published: February 2010

Humans are unique among mammals in that many consume cow's milk or other dairy products well beyond the traditional age of weaning. Milk provides various nutrients and bioactive molecules to support growth and development, and the question arises as to whether this dietary behavior influences growth parameters. There is evidence that milk makes positive contributions to growth in height, but its associations with other aspects of body size, such as body mass index (BMI), are not well‐established. National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 and multivariate regression analysis were used to test the hypothesis that milk (g) or total dairy product consumption (kJ) is associated with higher BMI percentile among US White, Black, and Mexican‐American children of age 2–4 years (n= 1,493) and 5–10 years (n= 2,526). Younger children in the highest quartile of dairy intake had higher BMIs (β = 7.5–8.0;P< 0.01) than those in the lowest two quartiles. Controlling for energy intake eliminated differences between QIV and QI. Among children of 5–10 years of age dairy intake had no relationship to BMI. Young children in the highest quartile of milk intake had higher BMIs than all lower quartiles (β = 7.1–12.8; β = 6.3–11.8 in energy‐controlled models;P< 0.05). Among children of 5–10 years of age, those in QIV for milk intake had higher BMIs than those in QII (β = 8.3; β = 7.1 in energy‐controlled model;P< 0.01). Controlling for total protein or calcium did not change the results. Milk had more consistent positive associations with BMI than did dairy products, and these were strongest among children of 2–4 years of age. Am. J. Hum. Biol., 2010. © 2010 Wiley‐Liss, Inc.
Pyrolysed powdered mussel shells for eutrophication control: effect of particle size and powder concentration on the mechanism and extent of phosphate removal
Authors: Abeynaike Arjan , Wang Luyao , Jones Mark I. , Patterson Darrell A.
Published: February 2010

The international shellfish farming industry has a growing problem with respect to sustainability: the shells, a by‐product, are currently being mostly wasted to landfill. Instead, this calcium‐rich resource can be used to produce lime [calcium oxide (CaO)] and then used to remove phosphate from rural wastewaters. Powdered mussel shell was heat treated to form lime. Two different shell particle sizes (fine, 53–106 µm; coarse, 212–250 µm) as well as various pyrolysis times, heating rates, pyrolysis temperatures and shell concentrations were used to determine the effects of these parameters on the lime formation and subsequent phosphate removal from a synthetic wastewater. Furthermore, the mechanisms of phosphate removal were determined by quantifying the phosphate content in all components before and after reaction with the synthetic wastewater. It was found that with excess of partially calcined pyrolysed shells, at a concentration of 5 g l−1, more than 95% phosphate removal was achieved, irrespective of particle size or pyrolysis conditions. When using optimally heat‐treated shells (particle size: 53–106 µm, pyrolysed for 1 h at 750 °C), it was possible to achieve over 90% phosphate removal using just 196 mg l−1 of shell. For the pyrolysed shells, the main mechanisms of phosphate removal were homogeneous nucleation to form a suspended precipitate, as well as adsorption and heterogeneous precipitation on the surface of the remaining calcite shell particles. Copyright © 2010 Curtin University of Technology and John Wiley & Sons, Ltd.
Adsorption kinetics of methane on a template‐synthesized carbon powder and its pellet
Authors: Guan Cong , Yang Chun , Wang Kean
Published: February 2010

Adsorptive storage of natural gas provides an alternative to the compression storage technology. Activated carbons can provide good storage capacity at relatively low cost. The volumetric storage capacity can be increased (two to three times) on carbon monoliths/pellets compared with the powdered form. The uptake rate and the effect of adsorption heat are important factors as the storage capacity must be realized rapidly for charging cycles.Methane adsorption kinetics was investigated on an activated carbon and its pellet in a batch adsorber at 298 K. The carbon was prepared by templated synthesis whereas the pellet was fabricated using a binderless method. Linear driving force (LDF) and Fickian diffusion (FD) models were utilized to study the kinetics. Both LDF and FD models can adequately describe the observed methane kinetics on the carbon samples when the dosing pressure > 5 bar. The heat of methane adsorption was found as high as 22 kJ/mol, and it plays an important role in the observed kinetic rates on both carbon powder and the pellet. The adsorption kinetics on the pellet appears to be slightly faster than that on the powder due to the quicker dissipation of the sorption heat. The LDF model is recommended for the study of methane uptake kinetics onto both carbon samples because of its simplicity and flexibility, and ability to model the data at both low and high sorption pressures. The effects of isotherm nonlinearity and surface heterogeneity were also discussed. Copyright © 2010 Curtin University of Technology and John Wiley & Sons, Ltd.
Inhibition of fibroblast activation protein and dipeptidylpeptidase 4 increases cartilage invasion by rheumatoid arthritis synovial fibroblasts
Authors: Ospelt Caroline , Mertens Joachim C. , Jüngel Astrid , Brentano Fabia , Maciejewska‐Rodriguez Hanna , Huber Lars C. , Hemmatazad Hossein , Wüest Thomas , Knuth Alexander , Gay Renate E. , Michel Beat A. , Gay Steffen , Renner Christoph , Bauer Stefan
Published: February 2010

Objective

Since fibroblasts in the synovium of patients with rheumatoid arthritis (RA) express the serine proteases fibroblast activation protein (FAP) and dipeptidylpeptidase 4 (DPP‐4)/CD26, we undertook the current study to determine the functional role of both enzymes in the invasion of RA synovial fibroblasts (RASFs) into articular cartilage.

Methods

Expression of FAP and DPP‐4/CD26 by RASFs was analyzed using fluorescence‐activated cell sorting and immunocytochemistry. Serine protease activity was measured by cleavage of fluorogenic substrates and inhibited upon treatment with L‐glutamyl L‐boroproline. The induction and expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in RASFs were detected using real‐time polymerase chain reaction. Densitometric measurements of MMPs using immunoblotting confirmed our findings on the messenger RNA level. Stromal cell–derived factor 1 (SDF‐1 [CXCL12]), MMP‐1, and MMP‐3 protein levels were measured using enzyme‐linked immunosorbent assay. The impact of FAP and DPP‐4/CD26 inhibition on the invasiveness of RASFs was analyzed in the SCID mouse coimplantation model of RA using immunohistochemistry.

Results

Inhibition of serine protease activity of FAP and DPP‐4/CD26 in vitro led to increased levels of SDF‐1 in concert with MMP‐1 and MMP‐3, which are downstream effectors of SDF‐1 signaling. Using the SCID mouse coimplantation model, inhibition of enzymatic activity in vivo significantly promoted invasion of xenotransplanted RASFs into cotransplanted human cartilage. Zones of cartilage resorption were infiltrated by FAP‐expressing RASFs and marked by a significantly higher accumulation of MMP‐1 and MMP‐3, when compared with controls.

Conclusion

Our results indicate a central role for the serine protease activity of FAP and DPP‐4/CD26 in protecting articular cartilage against invasion by synovial fibroblasts in RA.
ERK‐1/2 and p38 in the regulation of hypertrophic changes of normal articular cartilage chondrocytes induced by osteoarthritic subchondral osteoblasts
Authors: Prasadam Indira , van Gennip Stijn , Friis Thor , Shi Wei , Crawford Ross , Xiao Yin
Published: February 2010

Objective

Previous studies have shown the influence of subchondral bone osteoblasts (SBOs) on phenotypical changes of articular cartilage chondrocytes (ACCs) during the development of osteoarthritis (OA). The molecular mechanisms involved during this process remain elusive, in particular, the signal transduction pathways. The aim of this study was to investigate the in vitro effects of OA SBOs on the phenotypical changes in normal ACCs and to unveil the potential involvement of MAPK signaling pathways during this process.

Methods

Normal and arthritic cartilage and bone samples were collected for isolation of ACCs and SBOs. Direct and indirect coculture models were applied to study chondrocyte hypertrophy under the influence of OA SBOs. MAPKs in the regulation of the cell–cell interactions were monitored by phosphorylated antibodies and relevant inhibitors.

Results

OA SBOs led to increased hypertrophic gene expression and matrix calcification in ACCs by means of both direct and indirect cell–cell interactions. In this study, we demonstrated for the first time that OA SBOs suppressed p38 phosphorylation and induced ERK‐1/2 signal phosphorylation in cocultured ACCs. The ERK‐1/2 pathway inhibitor PD98059 significantly attenuated the hypertrophic changes induced by conditioned medium from OA SBOs, and the p38 inhibitor SB203580 resulted in the up‐regulation of hypertrophic genes in ACCs.

Conclusion

The findings of this study suggest that the pathologic interaction of OA SBOs and ACCs is mediated via the activation of ERK‐1/2 phosphorylation and deactivation of p38 phosphorylation, resulting in hypertrophic differentiation of ACCs.
Regulation of myeloperoxidase‐specific T cell responses during disease remission in antineutrophil cytoplasmic antibody–associated vasculitis: The role of Treg cells and tryptophan degradation
Authors: Chavele Konstantia‐Maria , Shukla Deepa , Keteepe‐Arachi Tracey , Seidel Judith Anna , Fuchs Dietmar , Pusey Charles D. , Salama Alan D.
Published: February 2010

Objective

T lymphocytes have been implicated in the pathogenesis of antineutrophil cytoplasmic antibody–associated vasculitis (AAV). Patients with myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA) experience relapses less frequently than those with proteinase 3 ANCA, suggesting greater immune regulation. This study was undertaken to investigate MPO‐specific T cell reactivity during disease remission and the factors regulating their responsiveness.

Methods

MPO‐specific T cells were quantified by enzyme‐linked immunospot assay with additional Treg cell depletion or exogenous interleukin‐2. Serum tryptophan and its metabolites were measured. In vivo blockade of indoleamine 2,3‐dioxygenase (IDO) was performed, and its effect on MPO reactivity was assessed.

Results

During disease remission, MPO‐specific interferon‐γ–producing T cell frequencies were comparable with those found in healthy controls and significantly lower than those found in patients with acute disease. CD4+CD25+ regulatory cells did not play a role in maintaining these low MPO‐specific T cell frequencies, since depletion of Treg cells did not augment MPO‐specific responses, and FoxP3 levels were diminished in patients compared with controls. Treg cell function, however, was comparable in patients and controls, suggesting numerical rather than functional deficiency. We found diminished serum tryptophan levels and elevated levels of its metabolite kynurenine in patients with MPO AAV as compared with controls. To confirm the effect of tryptophan degradation on MPO responses in vivo, we inhibited degradation in MPO‐immunized WKY rats and found greater immune responsiveness to MPO and a tendency to more severe glomerulonephritis.

Conclusion

Our findings indicate that MPO‐specific T cell frequencies are regulated during disease remission in association with tryptophan degradation. The tryptophan regulatory pathway is induced during active disease and persists during disease remission.
Assessment of cognitive function in systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis by computerized neuropsychological tests
Authors: Hanly John G. , Omisade Antonina , Su Li , Farewell Vernon , Fisk John D.
Published: February 2010

Objective

Computerized neuropsychological testing may facilitate screening for cognitive impairment in systemic lupus erythematosus (SLE). This study was undertaken to compare patients with SLE, patients with rheumatoid arthritis (RA), and patients with multiple sclerosis (MS) with healthy controls using the Automated Neuropsychological Assessment Metrics (ANAM).

Methods

Patients with SLE (n = 68), RA (n = 33), and MS (n = 20) were compared with healthy controls (n = 29). Efficiency of cognitive performance on 8 ANAM subtests was examined using throughput (TP), inverse efficiency (IE), and adjusted IE scores. The latter is more sensitive to higher cognitive functions because it adjusts for the impact of simple reaction time on performance. The results were analyzed using O'Brien's generalized least squares test.

Results

Control subjects were the most efficient in cognitive performance. MS patients were least efficient overall (as assessed by TP and IE scores) and were less efficient than both SLE patients (P = 0.01) and RA patients (P < 0.01), who did not differ. Adjusted IE scores were similar between SLE patients, RA patients, and controls, reflecting the impact of simple reaction time on cognitive performance. Thus, 50% of SLE patients, 61% of RA patients, and 75% of MS patients had impaired performance on ≥1 ANAM subtest. Only 9% of RA patients and 11% of SLE patients had impaired performance on ≥4 subtests, whereas this was true for 20% of MS patients.

Conclusion

ANAM is sensitive to cognitive impairment. While such computerized testing may be a valuable screening tool, our results emphasize the lack of specificity of slowed performance as a reliable indicator of impairment of higher cognitive function in SLE patients.
Simulation of sirolimus exposures and population variability immediately post renal transplantation: importance of the patient's CYP3A5 genotype in tailoring treatment
Authors: Lukas John C. , Calvo Rosario , Zografidis Anastasios , Ortega Ignacio , Suárez Elena
Published: February 2010

The rapid achievement of efficacious exposure to sirolimus (SRL) after renal transplantation is crucial. However, there is high unpredictability in the dose to exposure relationship. Part of the variation is related to patients originating from subpopulations of fast or slow metabolizers via the CYP3A5*1/*3 genotype. The probability of achieving therapeutic SRL blood concentrations for each subpopulation under two equal‐intensity increasing‐frequency protocols after the start of treatment was explored with Monte Carlo simulation. The population pharmacokinetic model and inter‐patient variability distributions of Djebli et al. (DRH2006) were sampled. They developed a base and final model with a genotype covariate for CL/F in patients receiving calcineurin inhibitor (CNI)‐free therapy with SRL, mycophenolate mofetil and corticosteroids. Fast metabolizers (expressers) had a CL/F of 28.3 l/h whilst slow metabolizers (non‐expressers) had a CL/F of 14.1 l/h. Here, in simulation, a standard 10 mg QD SRL was contrasted with a higher frequency of 5 mg BID SRL as related to the proportion of next dosed patients being within the 15–30 ng/ml trough levels on day 7 after transplantation. Near 0% of expressers on either regimen reached or exceeded the 30 ng/ml trough on day 7. Expressers showed protocol dependence for the chance of being within the 15–30 ng/ml range with the 5 mg BID protocol doubling those chances. Non‐expressers appeared less protocol dependent for the probability of being above or below the 15–30 ng/ml range. The ability to determine the genotype early on may help to rationalize the initial titration of individual patients receiving CNI‐free renal transplantation treatment with SRL. Copyright © 2010 John Wiley & Sons, Ltd.
A stopped‐flow study of the dual chemiluminescence for the luminol–KIO4–Mn2+ system in strong alkaline solutions
Authors: Huang Tsung‐Yuan , Lin Wann‐Yin
Published: February 2010

A novel phenomenon of dual chemiluminescence (CL) was observed for the KIO4–luminol–Mn2+ system in strong alkaline solutions using the stopped‐flow technique. Scavenging study of the reactive oxygen species (ROS) suggested that the two CL peaks originated from different CL pathways precipated by distinct ROS (O2− and •OH for the first peak, mainly 1O2 for the second peak). Generation of these ROS at different time intervals from the reactions involving IO4−, O2, and Mn2+ and their subsequent reactions with luminol induced the intense CL emission. The relative intensity of the two CL peaks can be tuned over a wide range by varying the concentrations of Mn2−, luminol and KIO4. Because of the involvement of different ROS in each pathway, the two CL peaks could respond quite differently to various substances. Moreover, variation of the intensity ratio of the two CL peaks altered the relative proportions of the corresponding ROS, thereby changing their responses to a given substance. The dual CL emission acts like a pair of tunable probes and it is believed that this CL system has great potential in analytical applications. Copyright © 2010 John Wiley & Sons, Ltd.
Propensity scored analysis of outcomes after ruptured abdominal aortic aneurysm
Authors: Holt P J E , Karthikesalingam A , Poloniecki J D , Hinchliffe R J , Loftus I M , Thompson M M
Published: February 2010

Background

This study examined the population outcome of ruptured abdominal aortic aneurysm (rAAA) in England, the role of endovascular repair (EVAR), and the relationship between outcome and hospital workload.

Methods

Data were retrieved from Hospital Episode Statistics between 1 April 2003 and 31 March 2008. Propensity scoring was used to compare the outcomes of stratified patients undergoing EVAR and open repair. The relationship between workload and outcome was determined.

Results

Some 3725 urgent and 4414 rAAA repairs were included. Mortality rates were 21·3 per cent for urgent repair and 46·3 per cent for rAAA repair. EVAR was employed for 16·3 and 7·6 per cent of urgent and rAAA repairs respectively. EVAR was associated with significantly reduced mortality for urgent repair (odds ratio (OR) 0·531, 95 per cent confidence interval 0·415 to 0·680; P < 0·001) and rAAA repair (OR 0·527, 0·416 to 0·668; P < 0·001). A propensity scored analysis confirmed the benefit of EVAR for rAAA repair (P < 0·001). Repair of rAAA at hospitals with a higher elective aneurysm workload was associated with lower mortality rates irrespective of the mode of treatment (P < 0·001). Higher-volume hospitals were more likely to operate on rAAA (P = 0·033).

Conclusion

EVAR offered a survival advantage over open repair for non-elective aneurysm procedures. Services for the treatment of rAAA should incorporate access to EVAR and would benefit from being based in units with a high elective caseload.
Randomized controlled trial of pelvic calcium alginate following rectal cancer surgery
Authors: Maggiori L , Rullier E , Meyer C , Portier G , Faucheron J L , Panis Y
Published: February 2010

Background

The aim of this randomized controlled trial was to assess the possible benefit of using a new haemostatic agent (Hémoionic®) in the pelvic cavity in sphincter-saving surgery for rectal cancer.

Methods

Eighty-five patients undergoing elective sphincter-saving rectal resection for cancer were randomized into Hémoionic® (41 patients) and control (44) groups. In both groups, a pelvic suction drain was left in place for as long as the daily output exceeded 20 ml. The primary endpoint was volume of fluid collected by the suction drain; secondary endpoints were duration of drainage, and postoperative mortality and morbidity rates.

Results

The mean total drainage volume was significantly lower in the Hémoionic® group (453 ml versus 758 ml in control group; P = 0·031). There was no significant difference between groups in duration of drainage and morbidity. The mortality rate was four of 41 in the Hémoionic® group and one of 44 in the control group (P = 0·192).

Conclusion

Hémoionic® may reduce the drainage volume after sphincter-saving surgery for rectal cancer, but offers no clinical advantage. Registration number: ISRCTN79721331 (http://www.isrctn.org).
Laparoscopic resection with transcolonic specimen extraction for ileocaecal Crohn's disease
Authors: Eshuis E J , Voermans R P , Stokkers P C F , van Berge Henegouwen M I , Fockens P , Bemelman W A
Published: February 2010

Background

Ileocolic resection for Crohn's disease can be performed entirely laparoscopically. However, an incision is needed for specimen extraction. This prospective observational study assessed the feasibility of endoscopic transcolonic specimen removal.

Methods

Endoscopic specimen removal was attempted in a consecutive series of ten patients scheduled for laparoscopic ileocolic resection. Primary outcomes were feasibility, operating time, reoperation rate, pain scores, morphine requirement and hospital stay. To assess applicability, outcomes were compared with previous data from patients who had laparoscopically assisted operations.

Results

Transcolonic removal was successful in eight of ten patients; it was considered not feasible in two patients because the inflammatory mass was too large (7–8 cm). Median operating time was 208 min and median postoperative hospital stay was 5 days. After surgery two patients developed an intra-abdominal abscess, drained laparoscopically or percutaneously, and one patient had another site-specific infection. The operation took longer than conventional laparoscopy, with no benefits perceived by patients in terms of cosmesis or body image.

Conclusion

Transcolonic removal of the specimen in ileocolic Crohn's disease is feasible in the absence of a large inflammatory mass but infection may be a problem. It is unclear whether the technique offers benefit compared with conventional laparoscopic surgery.
Transradial carotid stenting in a patient with bovine arch anatomy
Authors: Gan Hwa Wooi , Bhasin Anuj , Wu Chiung‐Jen
Published: February 2010

Carotid stenting in difficult arch anatomy can be safely done by transradial route depending upon operator's experience. Left carotid artery stenosis with Bovine arch anatomy can be approached by right arm approach (radial/brachial) easily. In cases with Bovine arch anatomy, left arm approach by modified looping technique is still possible. We report a case of carotid stenting in a patient with bovine arch anatomy using percusurge anchoring technique through left radial approach. © 2010 Wiley‐Liss, Inc.
Towards Solar Fuels from Water and CO2
Authors: Centi Gabriele , Perathoner Siglinda
Published: February 2010

Solar fuels from water and CO2 are a topic of current large scientific and industrial interest. Research advances on bioroutes, concentrated solar thermal and low‐temperature conversion using semiconductors and a photoelectrocatalytic (PEC) approach, are critically discussed and compared in an attempt to define challenges and current limits and to identify the priorities on which focus research and development (R&D). The need to produce fuels that are easy to transport and store, which can be integrated into the existing energy infrastructure, is emphasized. The role of solar fuels produced from CO2 in comparison with solar H2 is analyzed. Solar fuels are complementary to solar to electrical energy conversion, but they still need intensified R&D before possible commercialization.
Development of otolith receptors in Japanese quail
Authors: Huss David , Navaluri Rena , Faulkner Kathleen F. , David Dickman J.
Published: February 2010

This study examined the morphological development of the otolith vestibular receptors in quail. Here, we describe epithelial growth, hair cell density, stereocilia polarization, and afferent nerve innervation during development. The otolith maculae epithelial areas increased exponentially throughout embryonic development reaching asymptotic values near posthatch day P7. Increases in hair cell density were dependent upon macular location; striolar hair cells developed first followed by hair cells in extrastriola regions. Stereocilia polarization was initiated early, with defining reversal zones forming at E8. Less than half of all immature hair cells observed had nonpolarized internal kinocilia with the remaining exhibiting planar polarity. Immunohistochemistry and neural tracing techniques were employed to examine the shape and location of the striolar regions. Initial innervation of the maculae was by small fibers with terminal growth cones at E6, followed by collateral branches with apparent bouton terminals at E8. Calyceal terminal formation began at E10; however, no mature calyces were observed until E12, when all fibers appeared to be dimorphs. Calyx afferents innervating only Type I hair cells did not develop until E14. Finally, the topographic organization of afferent macular innervation in the adult quail utricle was quantified. Calyx and dimorph afferents were primarily confined to the striolar regions, while bouton fibers were located in the extrastriola and Type II band. Calyx fibers were the least complex, followed by dimorph units. Bouton fibers had large innervation fields, with arborous branches and many terminal boutons. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 436–455, 2010
Nanostructured Dioxomolybdenum(VI) Catalyst for the Liquid‐Phase Epoxidation of Olefins
Authors: Castro Alichandra , Alonso João C. , Valente Anabela A. , Neves Patrícia , Brandão Paula , Félix Vitor , Ferreira Paula
Published: February 2010

A new organosilica hybrid mesoporous material (HM) containing phosphane oxide surface groups was prepared via the “dual” organosilane templated co‐condensation of 4‐bis(triethoxysilyl)benzene and (diphenylphosphanyl)propyltriethoxysilane, followed by post‐synthesis oxidation of the phosphane surface groups. The HM material was used to immobilise the [Mo(O)2Cl2] complex. The resultant material (HM‐Mo) is an active and selective catalyst in the liquid‐phase epoxidation of olefins [cis‐cyclooctene, (R)‐(+)‐limonene, trans‐2‐octene, 1‐octene] with tBuOOH at 55 °C and gives comparable epoxide yields to those observed for the free complex [MoCl2(O)2{OP(CH2CH3)(Ph)2}2] (1), under similar reaction conditions: the crystal structure of complex 1 remains the same after reaction with tBuOOH. The oxidant is essentially consumed in the HM‐Mo or 1 catalysed epoxidation of the olefin. In the case of limonene (possesses endo‐ and exocyclic C=C bonds), the molar ratio of 1,2‐epoxy‐p‐menth‐8‐ene/1,2–8,9‐diepoxy‐p‐menthane at ca. 90 % conversion (reached after 24 h reaction) is ca. 5 and 10 for 1 and HM‐Mo, respectively, indicating a favourable regioselectivity towards the epoxidation of the endocyclic C1–C2 double bond, especially in the case of the heterogeneous catalyst.
Selective Tuning of the HOMO–LUMO Gap of Carbazole‐Based Donor–Acceptor–Donor Compounds toward Different Emission Colors
Authors: Zhang Huaqiang , Wan Xiangjian , Xue Xiaosong , Li Yanqin , Yu Ao , Chen Yongsheng
Published: February 2010

Carbazole‐based donor–acceptor compounds with tunable HOMO–LUMO gaps were synthesized by Suzuki and Sonogashira cross‐coupling reactions. Their optical and electrochemical properties were fully characterized. The results show that materials with different emission colors ranging from blue to green to orange could be obtained. The experimental results were also supported by theoretical calculations.
Nafion Coated Silver Amalgam Electrode for Determination of Trace Metals by Anodic Stripping Voltammetry
Authors: Strasunske Kristina , Mikkelsen Øyvind , Billon Gabriel
Published: February 2010

This paper describes characterization and application of Nafion coated solid silver amalgam electrodes to prevent surface fouling of surfactants in determination of trace metals by differential pulse anodic stripping voltammetry (DPASV). Polymer films of different thickness were tested using Nafion solutions in the range 0.25%–1%. Optimum thickness was archived using a 0.5% Nafion solution, resulting in both increased response and stability over time compared to uncoated electrodes. The influence of model surface active macromolecules was studied using triton X‐100, sodium dodecyl sulfate, dodecyl pyridinium chloride and bovine serum albumin as representatives for surfactants. The resistance to surfactants makes the studied Nafion coated solid silver amalgam electrodes an interesting alternative for practical use in environmental monitoring.