bluuebunny/crossref_metadata_2025 huggingface dataset:
High levels of inflammatory chemokines and cytokines in joint fluid and synovial tissue throughout the course of antibiotic‐refractory lyme arthritis
Authors: Shin Junghee J. , Glickstein Lisa J. , Steere Allen C.
Published: March 2007

Objective

To investigate the possible role of chemokines and cytokines in the pathogenesis of Lyme arthritis.

Methods

Using cytometric bead array and flow cytometry techniques, chemokine and cytokine levels were determined in 65 synovial fluid (SF) samples and 7 synovial tissue (ST) samples from 17 patients with antibiotic‐responsive Lyme arthritis and 35 patients with antibiotic‐refractory Lyme arthritis seen during the past 18 years. In the ST samples, expression of chemokine receptors was measured using immunohistochemistry.

Results

Before or during antibiotic therapy, when the majority of patients had positive polymerase chain reaction (PCR) results for Borrelia burgdorferi DNA, SF from patients with antibiotic‐refractory arthritis contained exceptionally high levels of Th1 chemoattractants and cytokines, particularly CXCL9 and interferon‐γ (IFNγ). Compared with the patients whose arthritis was responsive to antibiotic treatment, those with antibiotic‐refractory arthritis had significantly higher levels of CXCL9 and CXCL10 (both P ≤ 0.001) and CCL3, CCL4, CXCL8, IFNγ, tumor necrosis factor α, interleukin‐1β (IL‐1β), and IL‐6 (all P ≤ 0.01). During the post‐antibiotic period, when the results of PCR for B burgdorferi DNA in SF and ST were uniformly negative, patients with antibiotic‐refractory arthritis continued to exhibit high SF and ST levels of these chemokines and cytokines. In addition, synovial samples showed marked expression of the receptors for T cell or macrophage chemokines, CXCR3 and CCR5.

Conclusion

Patients with antibiotic‐refractory Lyme arthritis have high synovial fluid levels of proinflammatory chemokines and cytokines, especially CXCL9 and IFNγ, throughout the illness. Thus, even when antibiotic treatment reduces or completely clears the infection in these patients, the inflammatory response in synovium persists.
Interferon‐γ regulates susceptibility to collagen‐induced arthritis through suppression of interleukin‐17
Authors: Chu Cong‐Qiu , Swart David , Alcorn Dina , Tocker Joel , Elkon Keith B.
Published: March 2007

Objective

The enhanced expression of experimental arthritis in the absence of interferon‐γ (IFNγ) suggests that IFNγ suppresses arthritis. Interleukin‐17 (IL‐17) is a pivotal T cell cytokine in arthritis, and in vitro studies have indicated that IFNγ suppresses IL‐17 production. We undertook this study to test the hypothesis that resistance to collagen‐induced arthritis (CIA) in C57BL/6 (B6) mice is regulated by IFNγ‐mediated suppression of IL‐17.

Methods

Wild‐type (WT) B6 mice, IFNγ‐knockout (KO) B6 mice, and DBA/1 mice were immunized with type II collagen (CII) in Freund's complete adjuvant (CFA). Lymphocytes from immunized mice were analyzed for cytokine production ex vivo by intracellular staining or restimulation with CII and enzyme‐linked immunosorbent assays. In vivo blockade of IL‐17 was achieved with an anti–IL‐17 monoclonal antibody (mAb).

Results

CII restimulation of T cells from CII/CFA‐immunized mice resulted in an ∼5‐fold increase in IL‐17 production in IFNγ‐KO B6 mice compared with WT B6 mice. Neutralization of IFNγ increased IL‐17 production in WT B6 mice, and neutralization of IL‐4 had a synergistic effect. Interestingly, the prototypical CIA‐susceptible strain DBA/1 also demonstrated a high IL‐17 and a low IFNγ cytokine profile compared with WT B6 mice. Administration of the anti–IL‐17 mAb attenuated arthritis in DBA/1 mice and almost completely prevented expression of arthritis in IFNγ‐KO B6 mice.

Conclusion

These results indicate that sensitivity of IFNγ‐deficient B6 mice to CIA is associated with high IL‐17 production and that this cytokine is required for expression of arthritis in this strain.
Aberrant expression of BAFF by B lymphocytes infiltrating the salivary glands of patients with primary Sjögren's syndrome
Authors: Daridon Capucine , Devauchelle Valérie , Hutin Pascal , Berre Rozenn Le , Martins‐Carvalho Christine , Bendaoud Boutahar , Dueymes Maryvonne , Saraux Alain , Youinou Pierre , Pers Jacques‐Olivier
Published: March 2007

Objective

To identify the cells that produce BAFF in the salivary glands of patients with primary Sjögren's syndrome (SS), and to analyze BAFF receptor expression by local T and B lymphocytes.

Methods

We used 3 methods to identify the source of BAFF: in situ hybridization of the transcripts for BAFF combined with staining of membrane markers, regular and real‐time reverse transcription–polymerase chain reaction (RT‐PCR) of cultured epithelial cells, and RT‐PCR of sorted single‐cell T and B lymphocytes eluted from salivary glands. Cells expressing TACI, BCMA, and B lymphocyte stimulator receptor 3 (BR‐3) were disclosed by combining each specific staining of the receptors with each specific staining of the cells. The function of BAFF generated by epithelial cells on B lymphocytes was determined in short‐term cocultures.

Results

Transcripts for BAFF were seen in epithelial cells and infiltrating T lymphocytes and, for the first time, were detected in local B cells. It is interesting that BR‐3 was present on these B cells but not on T cells. In contrast, TACI and, to a lesser degree, BCMA were observed on transitional B lymphocytes, whereas T lymphocytes were devoid of receptors for BAFF. Furthermore, this cytokine was shown to be functional, in that epithelial cell–bound BAFF extended the survival of normal B cells, but cell‐free BAFF released in the supernatants did not.

Conclusion

These experiments establish that in primary SS, BAFF is produced not only by epithelial cells and T cells but also by B cells. The expression of receptors for BAFF would thus allow these receptors to participate in an autocrine pattern of self‐stimulation.
Arthritic pain is processed in brain areas concerned with emotions and fear
Authors: Kulkarni B. , Bentley D. E. , Elliott R. , Julyan P. J. , Boger E. , Watson A. , Boyle Y. , El‐Deredy W. , Jones A. K. P.
Published: March 2007

Objective

Functional neuroimaging studies have shown that experimentally induced acute pain is processed within at least 2 parallel networks of brain structures collectively known as the pain matrix. The relevance of this finding to clinical pain is not known, because no direct comparisons of experimental and clinical pain have been performed in the same group of patients. The aim of this study was to compare directly the brain areas involved in processing arthritic pain and experimental pain in a group of patients with osteoarthritis (OA).

Methods

Twelve patients with knee OA underwent positron emission tomography of the brain, using 18F‐fluorodeoxyglucose (FDG). Scanning was performed during 3 different pain states: arthritic knee pain, experimental knee pain, and pain‐free. Significant differences in the neuronal uptake of FDG between different pain states were investigated using statistical parametric mapping software.

Results

Both pain conditions activated the pain matrix, but arthritic pain was associated with increased activity in the cingulate cortex, the thalamus, and the amygdala; these areas are involved in the processing of fear, emotions, and in aversive conditioning.

Conclusion

Our results suggest that studies of experimental pain provide a relevant but quantitatively incomplete picture of brain activity during arthritic pain. The search for new analgesics for arthritis that act on the brain should focus on drugs that modify this circuitry.
Selective therapeutic control of C5a and the terminal complement complex by anti‐C5 single‐chain Fv in an experimental model of antigen‐induced arthritis in rats
Authors: Fischetti Fabio , Durigutto Paolo , Macor Paolo , Marzari Roberto , Carretta Renzo , Tedesco Francesco
Published: March 2007

Objective

To determine the role of the terminal complement complex (TCC) in the development of experimental antigen‐induced arthritis (AIA) and the therapeutic effects of human anti‐C5 single‐chain Fv (scFv).

Methods

Two different anti‐C5 scFv, one that inhibits both release of C5a and assembly of the TCC (TS‐A 12/22) and another that selectively blocks formation of the TCC (TS‐A 8), were injected at the onset of AIA. The effects of these scFv on disease severity were evaluated for up to 21 days and compared with the effects of injection of an unrelated scFv. AIA was also established in C6‐deficient and C6‐sufficient PVG rats to obtain further information on the role of the TCC in this model.

Results

TS‐A 12/22 and TS‐A 8 proved to be equally effective in reducing joint swelling, cell counts and tumor necrosis factor α levels in synovial lavage fluids, and the degree of histomorphologic changes compared with the effects of the unrelated scFv. TS‐A 12/22 and TS‐A 8 prevented the deposition of C9 but not that of C3, confirming the ability of the 2 scFv to neutralize C5. Administration of the 2 anti‐C5 scFv after AIA onset also reduced disease severity. In C6‐deficient rats with AIA, disease activity was reduced markedly compared with that in C6‐sufficient rats.

Conclusion

These 2 human anti‐C5 scFv could represent potential therapeutic reagents to be used in patients with rheumatoid arthritis. In addition, the finding that TS‐A 8 was as effective as TS‐A 12/22 in reducing disease severity suggests that the TCC is mainly responsible for the joint inflammation and damage observed in AIA.
Light up‐regulated on B lymphocytes and monocytes in rheumatoid arthritis mediates cellular adhesion and metalloproteinase production by synoviocytes
Authors: Kang Young Mo , Kim So Young , Kang Jin Hee , Han Seung Woo , Nam Eon Jeong , Kyung Hee Soo , Park Jae Yong , Kim In San
Published: March 2007

Objective

To study the expression of LIGHT (tumor necrosis factor superfamily 14) and herpesvirus entry mediator (HVEM; tumor necrosis factor receptor superfamily 14) in rheumatoid arthritis (RA) and to determine the regulatory role of LIGHT on the effector functions of fibroblast‐like synoviocytes (FLS).

Methods

The expression of LIGHT and HVEM was assessed by immunohistochemical staining of synovial tissue and by flow cytometric analysis of mononuclear cells. The presence of HVEM and lymphotoxin β receptor was measured by reverse transcriptase–polymerase chain reaction and by flow cytometry. The regulation of effector molecules, including matrix metalloproteinases (MMPs) and adhesion molecules, was evaluated. The adhesiveness of FLS was determined by adhesion assay.

Results

HVEM was detected in most cell types within rheumatoid synovial tissue, while only a few cells were positive for LIGHT. In RA patients, LIGHT expression was significantly up‐regulated only in CD20+ B cells and monocytes, whereas the mean fluorescence intensity of HVEM was down‐regulated in mononuclear cells. The stimulation of FLS with LIGHT resulted in the production of MMPs and the expression of adhesion molecules, which were efficiently inhibited by dexamethasone. LIGHT‐mediated up‐regulation of MMPs and intercellular adhesion molecule 1 was blocked by inhibitors of NF‐κB and JNK, whereas up‐regulation of vascular cell adhesion molecule 1 was blocked by inhibitors of phosphatidylinositol 3‐kinase, as well as NF‐κB.

Conclusion

These data suggest that binding of LIGHT with its receptors may play a role in the progression of inflammation within rheumatoid synovium, especially by mediating the interactions between infiltrating inflammatory cells and stromal cells. These findings thus emphasize the relevance of LIGHT as a potential therapeutic target in RA.
Bone erosions and bone marrow edema as defined by magnetic resonance imaging reflect true bone marrow inflammation in rheumatoid arthritis
Authors: Jimenez‐Boj Esther , Nöbauer‐Huhmann Iris , Hanslik‐Schnabel Beatrice , Dorotka Ronald , Wanivenhaus Axel‐Hugo , Kainberger Franz , Trattnig Siegfried , Axmann Roland , Tsuji Wayne , Hermann Sonja , Smolen Josef , Schett Georg
Published: March 2007

Objective

To investigate the pathologic nature of features termed “bone erosion” and “bone marrow edema” (also called “osteitis) on magnetic resonance imaging (MRI) scans of joints affected by rheumatoid arthritis (RA).

Methods

RA patients scheduled for joint replacement surgery (metacarpophalangeal or proximal interphalangeal joints) underwent MRI on the day before surgery. The presence and localization of bone erosions and bone marrow edema as evidenced by MRI (MRI bone erosions and MRI bone marrow edema) were documented in each joint (n = 12 joints). After surgery, sequential sections from throughout the whole joint were analyzed histologically for bone marrow changes, and these results were correlated with the MRI findings.

Results

MRI bone erosion was recorded based on bone marrow inflammation adjacent to a site of cortical bone penetration. Inflammation was recorded based on either invading synovial tissue (pannus), formation of lymphocytic aggregates, or increased vascularity. Fat‐rich bone marrow was replaced by inflammatory tissue, increasing water content, which appears as bright signal enhancement on STIR MRI sequences. MRI bone marrow edema was recorded based on the finding of inflammatory infiltrates, which were less dense than those of MRI bone erosions and localized more centrally in the joint. These lesions were either isolated or found in contact with MRI bone erosions.

Conclusion

MRI bone erosions and MRI bone marrow edema are due to the formation of inflammatory infiltrates in the bone marrow of patients with RA. This emphasizes the value of MRI in sensitively detecting inflammatory tissue in the bone marrow and demonstrates that the inflammatory process extends to the bone marrow cavity, which is an additional target structure for antiinflammatory therapy.
Structural insertion/deletion variation in IRF5 is associated with a risk haplotype and defines the precise IRF5 isoforms expressed in systemic lupus erythematosus
Authors: Kozyrev Sergey V. , Lewén Susanna , Reddy Prasad M. V. Linga , Pons‐Estel Bernardo ,   Argentine Collaborative Group, Witte Torsten ,   German Collaborative Group, Junker Peter , Laustrup Helle , Gutiérrez Carmen , Suárez Ana , Francisca González‐Escribano Maria , Martín Javier ,   Spanish Collaborative Group, Alarcón‐Riquelme Marta E.
Published: March 2007

Objective

To determine whether specific isoforms of IRF5 are transcribed in patients with systemic lupus erythematosus (SLE) who have risk genotypes in the exon 1B donor splice site at single‐nucleotide polymorphism (SNP) no. rs2004640.

Methods

Peripheral blood mononuclear cells were obtained from SLE patients and healthy controls from Argentina, Spain, and Germany and from trio families from Spain and Denmark. A reporter assay was used to investigate the role of SNP no. rs2004640. IRF5 expression in relation to the genotypes of functional SNPs was analyzed using quantitative polymerase chain reaction. Sequencing and genotyping of the IRF5 gene was performed.

Results

Sequencing of complementary DNA from individuals with different genotypes showed 4 basic isoforms transcribed from all 5′‐untranslated regions (5′‐UTRs), suggesting no preferential isoform transcription based on rs2004640 genotypes. Analysis of translation efficiency showed that exon 1A was the most efficient in initiating protein synthesis. We identified a novel polymorphic insertion/deletion that defines the pattern of expression of isoforms of IRF5. The insertion consists of 4 repeats in exon 6 affecting the protein interaction domain. The insertion segregates in the risk haplotype with the high expression allele of a poly(A) site SNP no. rs10954213 and the exon 1B donor splice allele of the 5′‐UTR SNP no. rs2004640. The poly(A) polymorphism correlated with levels of IRF5 in cells stimulated with interferon‐α. The SNP most strongly associated with SLE was SNP no. rs2070197 (P = 5.2 × 10−11), which is a proxy of the risk haplotype, but does not appear to be functional.

Conclusion

None of the functional variants investigated in this study is strongly associated with SLE, with the exception of the exon 1B donor splice site, and its functional importance appears to be small. Our results suggest that there may be other functional polymorphisms, yet to be identified, in IRF5. We did not observe evidence of epistatic interaction between the functional SNPs.
Risk of serious bacterial infections among rheumatoid arthritis patients exposed to tumor necrosis factor α antagonists
Authors: Curtis Jeffrey R. , Patkar Nivedita , Xie Aiyuan , Martin Carolyn , Allison Jeroan J. , Saag Michael , Shatin Deborah , Saag Kenneth G.
Published: March 2007

Objective

To evaluate the risk of serious bacterial infections associated with tumor necrosis factor α (TNFα) antagonists among rheumatoid arthritis (RA) patients.

Methods

A retrospective cohort study of US RA patients enrolled in a large health care organization identified patients who received either TNFα antagonists or methotrexate (MTX). Administrative data were used to identify hospitalizations with possible bacterial infections; corresponding medical records were abstracted and reviewed by infectious disease specialists for evidence of definite infections. Proportional hazards models evaluated time‐dependent infection risks associated with TNFα antagonists.

Results

Hospital medical records with claims‐identified suspected bacterial infections were abstracted (n = 187) among RA patients who received TNFα antagonists (n = 2,393; observation time 3,894 person‐years) or MTX (n = 2,933; 4,846 person‐years). Over a median followup time of 17 months, the rate of hospitalization with a confirmed bacterial infection was 2.7% among the patients treated with TNFα antagonists compared with 2.0% among the patients treated with MTX only. The multivariable‐adjusted hazard ratio (HR) of infection among the patients who received TNFα antagonists was 1.9 (95% confidence interval [95% CI] 1.3–2.8) compared with patients who received MTX only. The incidence of infections was highest within 6 months after initiating TNFα antagonist therapy (2.9 versus 1.4 infections per 100 person‐years; multivariable‐adjusted HR 4.2, 95% CI 2.0–8.8).

Conclusion

The multivariable‐adjusted risk of hospitalization with a physician‐confirmed definite bacterial infection was ∼2‐fold higher overall and 4‐fold higher in the first 6 months among patients receiving TNFα antagonists versus those receiving MTX alone. RA patients were at increased risk of serious infections, irrespective of the method used to define an infectious outcome. Patients and physicians should vigilantly monitor for signs of infection when using TNFα antagonists, particularly shortly after treatment initiation.
Interstitial pneumonitis in Blau syndrome with documented mutation in CARD15
Authors: Becker Mara L. , Martin Tammy M. , Doyle Trudy M. , Rosé Carlos D.
Published: March 2007

This is the first report of a CARD15 mutation–positive patient with Blau syndrome who exhibited interstitial lung disease, a feature historically considered absent from Blau syndrome, while typical of the adult form of sarcoidosis. This case illustrates the continued evolution of the phenotype of a disease initially conceived as a familial inflammatory granulomatous disease limited to the triad of synovitis, dermatitis, and uveitis.
Association between valgus and varus alignment and the development and progression of radiographic osteoarthritis of the knee
Authors: Brouwer G. M. , Tol A. W. Van , Bergink A. P. , Belo J. N. , Bernsen R. M. D. , Reijman M. , Pols H. A. P. , Bierma‐Zeinstra S. M. A.
Published: March 2007

Objective

Although knee malalignment is assumed to correlate with knee osteoarthritis (OA), it is still unknown whether malalignment precedes the development of OA or whether it is a result of OA. The aim of this study was to assess the relationship between malalignment and the development of knee OA as well as progression of knee OA.

Methods

A total of 1,501 participants in the Rotterdam study were randomly selected. Knee OA at baseline and at followup (mean followup 6.6 years) was scored according to the Kellgren/Lawrence (K/L) grading system. Alignment was measured by the femorotibial angle on radiographs at baseline. Multivariable logistic regression for repeated measurements was used to analyze the association of malalignment with the development and progression of OA.

Results

Of 2,664 knees, 1,012 (38%) were considered to have normal alignment, 693 (26%) had varus alignment, and 959 (36%) had valgus alignment. A comparison of valgus alignment and normal alignment showed that valgus alignment was associated with a borderline significant increase in development of knee OA (odds ratio [OR] 1.54, 95% confidence interval [95% CI] 0.97–2.44), and varus alignment was associated with a 2‐fold increased risk (OR 2.06, 95% CI 1.28–3.32). Stratification for body mass index showed that this increased risk was especially seen in overweight and obese individuals but not in non‐overweight persons. The risk of OA progression was also significantly increased in the group with varus alignment compared with the group with normal alignment (OR 2.90, 95% CI 1.07–7.88).

Conclusion

An increasing degree of varus alignment is associated not only with progression of knee OA but also with development of knee OA. However, this association seems particularly applicable to overweight and obese persons.
A randomized crossover trial of a wedged insole for treatment of knee osteoarthritis
Authors: Baker Kristin , Goggins Joyce , Xie Hui , Szumowski Karen , LaValley Michael , Hunter David J. , Felson David T.
Published: March 2007

Objective

In uncontrolled studies, a lateral‐wedge insole has reduced knee pain in patients with medial knee osteoarthritis (OA). The aim of this study was to test the efficacy of this simple, low‐cost intervention for pain in patients with medial knee OA.

Methods

We conducted a double‐blind, randomized, crossover trial designed to detect a small effect of treatment. Participants were at least 50 years of age and had medial joint space narrowing on posteroanterior semiflexed radiographs and scores indicating moderate pain for 2 of the 5 items on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale. Participants were randomized to receive a 5° lateral‐wedge insole or a neutral insole for 6 weeks. Following a 4‐week washout period, participants crossed over to the other treatment for 6 weeks. Knee pain, the primary outcome, was assessed by the WOMAC pain scale (visual analog scale version). Secondary outcomes included the WOMAC disability subscale, overall knee pain, 50‐feet walk time, chair‐stand time, and use of medications for knee pain.

Results

Ninety patients were randomized. The mean difference in pain between the 2 treatments was 13.8 points on the WOMAC pain scale (95% confidence interval −3.9, 31.4 [P = 0.13]). We observed similar small effects for the secondary outcomes.

Conclusion

The effect of treatment with a lateral‐wedge insole for knee OA was neither statistically significant nor clinically important.
Probabilistic models for medical insurance claims
Authors: Tessera Abebe
Published: March 2007

The paper develops two probabilistic models for claim size in health insurance based on the claims of families and individuals covered by the policy. First, general models for the numbers of families and persons covered by a medical insurance are developed. These are then used to construct models for claim size. Applications of these general models are then analysed and discussed. Copyright © 2007 John Wiley & Sons, Ltd.
Achieving the educational standards we need
Authors: Stewart Donald M.
Published: March 2007

This article is based on remarks presented by Donald M. Stewart at the Open Forum on National Standards held at the Second National Conference on School/College Collaboration, cosponsored by the American Association for Higher Education and the College Board in Atlanta, Georgia, on July 26, 1991.
Assessment as an episode of learning
Authors: Wolf Dennis Palmer
Published: March 2007

This article is an excerpt of a research report by the same title. An earlier version of the report will appear as a chapter in R. Bennett and W. Ward (eds.), Construction Versus Choice in Cognitive Measurement, to be published by Lawrence Earlbaum Associates.
Assessment of general education at Clayton State College
Authors: Rice Bradley R. , McElroy Elliott W.
Published: March 2007

This article is an excerpt from a report issued by Clayton State College and from an article by B. R. Rice and E. W. McElroy, “General Education at Clayton State College” in Outcomes: The Quarterly Journal of the Network for Outcome‐Based Schools, 10 (1), Spring 1991.
It's Déjà vu all over again: Assessment in Great Britain
Authors: Smith Terry B.
Published: March 2007

The author gratefully acknowledges the Fulbright U.S.‐U.K. Academic Administrator Fellowship program for making his work in Great Britain possible and Dr. Peter Findlay at Portsmouth Polytechnic in England for his editorial assistance.
Poland syndrome associated with an aberrant subclavian artery and vascular abnormalities of the retina in a child exposed to misoprostol during pregnancy
Authors: Rosa Rafael Fabiano Machado , Travi Giovanni M. , Valiatti Fabiana , Zen Paulo Ricardo Gazzola , Pinto Louise Lapagesse , Kiss Andrea , Graziadio Carla , Paskulin Giorgio Adriano
Published: March 2007

BACKGROUND:Poland syndrome has been attributed to a process of vascular disruption, and exposure to misoprostol at 6–8 weeks of gestation has been shown to produce defects attributed to vascular disruption. Herein we report the first case of a patient with Poland syndrome associated with an aberrant subclavian artery and vascular abnormalities of the retina, whose mother used misoprostol during pregnancy.CASE:A White boy of 1 year and 7 months of age, whose mother used misoprostol during the second month of pregnancy, presented with bilateral epicanthal folds, aplasia of the sternocostal head of the pectoralis major muscle with a hypoplastic nipple on the right side, and asymmetry between the upper limbs. The results of an angiotomographic study showed the presence of an aberrant right subclavian artery. Ultrasonographic evaluation showed turbulence and a high peak in the diastolic velocity in both carotid arteries, suggesting stenosis. Ophthalmologic assessment disclosed an intense bilateral tortuosity of the retinal blood vessels, with arterialnarrowing and rarefaction of the retinal pigment epithelium.CONCLUSIONS:This case suggests that the mechanism of vascular disruption of misoprostol could be related to the aberrant subclavian artery and the observed Poland syndrome. His retinal findings are different from those in cases described thus far in the literature, and this pattern of anomaly has never been associated with a gestational exposure to misoprostol. The possibility of a relationship of the aberrant right subclavian artery and the pattern of blood flow verified in the carotid arteries with the eye fundus abnormalities could be causally related or simply coincidental. Birth Defects Research (Part A), 2007. © 2007 Wiley‐Liss, Inc.
Behavior modification and the principle of normalization: clash or synthesis?
Authors: Ntinas Konstantinos M.
Published: March 2007

The aim of this article is to analyze the relationship between the principle of normalization and behavior modification with reference to the use of moderate punishment. Applying the normalization ideology through non‐aversive strategies alone has resulted in poor outcomes. Research demonstrates that moderate punishment can be a useful aid towards the development of normative interventions. In this way the negative implications of the dogmatic equation of ‘normativeness’ with non‐aversiveness on the effectiveness of intervention are avoided. Copyright © 2007 John Wiley & Sons, Ltd.
The non‐problem of free will in forensic psychiatry and psychology
Authors: Morse Stephen J.
Published: March 2007

This article demonstrates that there is no free will problem in forensic psychiatry by showing that free will or its lack is not a criterion for any legal doctrine and it is not an underlying general foundation for legal responsibility doctrines and practices. There is a genuine metaphysical free will problem, but the article explains why it is not relevant to forensic practice. Forensic practitioners are urged to avoid all usage of free will in their forensic thinking and work product because it is irrelevant and spawns confusion. Copyright © 2007 John Wiley & Sons, Ltd.
Free will in context: a contemporary philosophical perspective
Authors: Grim Patrick
Published: March 2007

Philosophical work on free will is inevitably framed by the problem of free will and determinism. This paper offers an overview of the current state of the philosophical art. Early sections focus on quantum indeterminism, an outline of the most influential logical argument for incompatibilism between free will and determinism, and telling problems that face incompatibilism. A major portion of the paper focuses on the compatiblist alternative, favored by many working philosophers. The conditional account of free will offered by classical compatibilism can be shown to be inadequate. A number of compatibilist options remain open, however, and seem promising for future research. These include ‘hierarchical’ or ‘mesh’ accounts of free will, normative perspectives and an approach to free will in terms of an emphasis on context. Final sections draw out the implications of contemporary compatibilism for the brain and behavioral sciences and for the law. Copyright © 2007 John Wiley & Sons, Ltd.
A brief history of the concept of free will: issues that are and are not germane to legal reasoning
Authors: Cary Phillip
Published: March 2007

Examining the history of the concept of free will helps distinguish metaphysical issues beyond the interest of a court of law from considerations about the nature of human action germane to legal reasoning. The latter include Plato's conception of the rational governance of the soul and Aristotle's conception of voluntary action, both of which arose before Hellenistic philosophers propounded analogues of modern positions against determinism (Epicureans) or for the compatibility of free will and determinism (Stoics). The concept of will itself also has a history, being first conceived as a distinct power by Augustine. Modern physics raised new problems about free will, as human motivations began to look less like rational perceptions of the good and more like mechanistic causes. Contemporary philosophy has not solved the problem of free will but has spun off analyses of the nature of action and moral responsibility that are of interest for legal reasoning. Copyright © 2007 John Wiley & Sons, Ltd.
The historical debate on brain and legal responsibility—revisited
Authors: Kroeber Hans‐Ludwig
Published: March 2007

The actual discussion on brain research, free will, and legal responsibility repeats all the arguments of a very similar discussion in central Europe 100 years ago, around 1900. Already back then the idea that human perception, emotions, thinking and behavior have a material basis was not new. It is conditioned and limited by the structure and workings of the brain. This applies to sane and sick brains alike. In this debate criminality was made a topic of biology by interpreting it as a symptom of genetic “degeneration”. In regard to brain damage in humans with socially deviant behavior, psychiatry claimed responsibility for a large proportion of criminals. This article lays out some important positions of psychiatry and jurisprudence in this debate on the foundations of legal responsibility and their impact up to now. The debate leads to the conclusion that human behavior cannot be described adequately in physical terms of cause and effect. The psychological approach to describe reasons, motives and intentions is substantially more appropriate. This method is also accepted by criminal law. Copyright © 2007 John Wiley & Sons, Ltd.
Common components and specific weight analysis and multiple co‐inertia analysis applied to the coupling of several measurement techniques
Authors: Hanafi M. , Mazerolles G. , Dufour E. , Qannari E. M.
Published: March 2007

The present paper compares two multiblock techniques: the Common Components and Specific Weights Analysis (CCSWA) and the Multiple Co‐inertia Analysis (MCoA). Both methods are used to (1) to investigate the relationships among various data tables and (2) to extract latent variables from information of different nature, reflecting different facets of a food product. Our objective is to study the ability of these methods to extract, from a set of data tables, latent characteristics which are representative of the whole modifications brought to a complex system (food product) by a modification of a given process factor. The comparison of these methods is based on the investigation of their conceptual framework by particularly highlighting new properties of CCSWA. Moreover, the two techniques of analysis are compared on the basis of a case study in cheese processing where each cheese sample is described by different kinds of measurements. Copyright © 2007 John Wiley & Sons, Ltd.
An Anthracene‐Appended β‐Cyclodextrin‐Based Dyad: Study of Self‐Assembly and Photoinduced Electron‐Transfer Processes
Authors: Balan Bijitha , Gopidas Karical R.
Published: March 2007

The self‐assembly of a β‐cyclodextrin (β‐CD)‐based supramolecular dyad is reported, in which the donor anthracene moiety is covalently linked to the smaller rim of the β‐CD and the acceptor pyromellitic diimide (PMDI) is encapsulated within the β‐CD cavity. Encapsulation of the PMDI into the β‐CD cavity was studied by a variety of techniques, which suggested that PMDI is encapsulated so as to position the aromatic part at the centre of the cavity with the 2‐propyl end at the narrower rim among the overhanging primary OH groups and the N‐ethylpyridinium end situated at the wider rim exposed to water. Photoinduced electron transfer (PET) in the system was studied by fluorescence quenching and laser flash photolysis techniques. At [PMDI]<10−4 M, the equilibrium is in favour of the free molecules, and under these conditions fluorescence quenching is negligible and diffusion‐mediated electron transfer involving the triplet excited state of anthracene predominates. At higher concentrations of PMDI, the equilibrium is largely in favour of the supramolecular dyad and intra‐ensemble PET processes predominate. The experimentally determined electron‐transfer rate constant agrees very well with that calculated by using the Marcus equation. It was observed that a fraction of the ion pairs survived for more than 200 μs.
Solution and Solid‐State Preparation of 18‐Crown[6] Complexes with M[HSO4]n Salts (M = NH4+, K+, Sr2+ and n = 1, 2) and an Investigation of Solvation/Desolvation Processes and Crystal Polymorphism
Authors: Braga Dario , Gandolfi Massimo , Lusi Matteo , Paolucci Demis , Polito Marco , Rubini Katia , Grepioni Fabrizia
Published: March 2007

18‐Crown[6] ether has been used to prepare a new class of organic–inorganic complexes of general formula 18‐crown[6]⋅M[HSO4]n (where M = NH4+, K+, Sr2+ and n = 1, 2) by reacting directly in solution or in the solid state the crown ether 18‐crown[6] with inorganic salts such as [NH4][HSO4], K[HSO4], and Sr[HSO4]2. The structures of 18‐crown[6]⋅[NH4][HSO4]⋅2 H2O (1⋅2 H2O), 18‐crown[6]⋅[NH4][HSO4] (1), 18‐crown[6]⋅K[HSO4]⋅2 H2O (2⋅2 H2O), 18‐crown[6]⋅K[HSO4] (2), and 18‐crown[6]⋅Sr[HSO4]2 (3) have been characterized by single‐crystal X‐ray diffraction. The reversible water loss in compounds 1⋅2 H2O and 2⋅2 H2O leads to formation of the corresponding anhydrous phases 18‐crown[6]⋅[NH4][HSO4] (1), and 18‐crown[6]⋅K[HSO4] (2), which undergo, on further heating, enantiotropic solid‐solid transitions very likely associated with the on‐set of a solid state dynamical process. Similar high‐temperature behavior is shown by 18‐crown[6]⋅Sr[HSO4]2 (3). The dehydration and phase‐transition processes have been investigated by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and variable temperature X‐ray powder diffraction.
Determination of the absolute configurations of flexible molecules: Synthesis and theoretical simulation of electronic circular dichroism/optical rotation of some pyrrolo[2,3‐b]indoline alkaloids—A case study
Authors: Giorgio Egidio , Tanaka Katsunori , Verotta Luisella , Nakanishi Koji , Berova Nina , Rosini Carlo
Published: March 2007

The paper describes the synthesis and chiroptical properties of (−)‐1,2,3,3a,8,8a,‐hexahydro‐1,3a‐dimethyl‐pyrrolo[2,3‐b]indole, (−)‐1, one of the monomeric units of many flexible polypyrroloindoline alkaloids and (−)‐chimonanthine, (−)‐2. The aim of this investigation is to show that, under certain circumstances, namely, with molecules for which the sign and order of magnitude of [α]D are determined by the lowest‐energy valence‐shell transitions (referred to as class (a) molecules), a small basis set calculation of chiroptical properties provides reliable results, and that such a treatment can be employed for absolute configurational assignment of larger oligomers, for which the increased flexibility renders the analysis as formidable task. Actually, as the aforementioned two molecules belong to class (a) systems, a TDDFT/B3LYP/6‐31G* calculation of the ECD and ORD spectra gives rise to a more than satisfactory simulation of these data, assuming the reported absolute configurations. In other words, the use of the TDDFT/B3LYP method with the small 6‐31G* basis set enables one to treat large and flexible molecules such as (−)‐2 (52 atoms and 6 conformers) by usage of a simple PC in about 2 weeks. This protocol demonstrates that an ab initio prediction of ECD/ORD spectra results in reliable assignments of absolute configuration of even relatively large natural products, thus economizing computation time. Chirality, 2007. © 2007 Wiley‐Liss, Inc.
Role of racemization in optically active drugs development
Authors: Ali Imran , Gupta Vinod K. , Aboul‐Enein Hassan Y. , Singh Prashant , Sharma Bhavtosh
Published: March 2007

U.S. Food and Drug Administration issues certain guidelines for marketing of optically active drugs as some enantiomers racemize into human body, leading to the generation of other antipodes, which may be toxic or ballast to the human beings. Moreover, racemization reduces the administrated dosage concentration as optically active enantiomer converted into its inactive counter part. Therefore, the study of racemization of such type of drugs is an important and urgent need of today. This article describes in vitro and in vivo racemization of optically active drugs. The racemization process of various optically active drugs has been discussed considering the effect of different variables i.e. pH, temperature, concentration of the drug, ionic concentration, etc. Attempts have also been made to discuss the mechanisms of racemization. Besides, efforts have been made to suggest the safe dosages of such type of drugs too. Chirality, 2007. © 2007 Wiley‐Liss, Inc.
NHC‐containing chiral bidentate ligands: Synthesis and evaluation in enantioselective copper‐catalyzed conjugate addition
Authors: Clavier Hervé , Guillemin Jean‐Claude , Mauduit Marc
Published: March 2007

New chiral phosphine‐, thiolate‐, mesylate‐, and tosylate‐containing N‐heterocyclic carbene ligands have been synthesized in fair to excellent yield. These bidentate ligands have been evaluated in enantioselective copper‐catalyzed conjugate addition to both cyclic and acyclic enones and displayed good catalytic activities and poor to good enantiomeric excesses (up to 80%). Chirality, 2007. © 2007 Wiley‐Liss, Inc.
Optimierung einer auf dem Verfahren der mechanischen Brüdenverdichtung basierenden Meerwasserentsalzungsanlage
Authors: Diezel L. L. , Fröba A. P. , Lukić N. , Leipertz A.
Published: March 2007

Eine Betrachtung des weltweiten Meerwasserentsalzungsmarktes zeigt, dass das Verfahren der mechanischen Brüdenverdichtung trotz seiner technischen Zuverlässigkeit und der Realisierung einer autarken dezentralen Betriebsweise nur einen geringen Marktanteil einnimmt. Der Grund hierfür liegt insbesondere im hohen spezifischen Trinkwasserpreis für dieses Verfahren. In dieser Arbeit wird eine Verbesserung der Effizienz des Verfahrens über die Ionenimplantation der wärmeübertragenden Flächen zur Intensivierung des Kondensations‐ und Verdampfungsprozesses vorgeschlagen. Dazu wird zunächst ein Modell entwickelt, das die notwendigen Wärmetransportmechanismen im Bereich der Verdampfer‐/Kondensatoreinheit für die Prozessenergien beschreibt.
Adsorption und Reaktion von NO an unterschiedlichen Aktivkohlen und ‐koksen
Authors: Klose W. , Rincón S.
Published: March 2007

Die Vorgänge, die bei der Adsorption und Reduktion von NO an Aktivkohle bzw. ‐koks ablaufen, werden von einer Vielzahl von Variablen beeinflusst. Aus den experimentellen Ergebnissen konnten keine Abhängigkeiten zwischen den physikalischen Eigenschaften der Aktivkohlen und ‐kokse und den ablaufenden Prozessen ermittelt werden. Die chemischen Eigenschaften der Oberfläche der Aktivkohle bzw. ‐kokse spielen eine sehr wichtige Rolle. Die Anwesenheit von Sauerstoffkomplexen und die katalytischen Effekte der mineralischen Komponenten der Asche sind für den Ablauf der Prozesse entscheidend.
Modell zur Berechnung des Wärmeüberganges in Rohren und Kanälen mit technischen Profilrauigkeiten
Authors: Pöhlmann M.
Published: March 2007

Beschrieben wird ein Modell zur Berechnung von Wärmeübergangskoeffizienten und Reibungsbeiwerten in Rohren bzw. Kanälen mit künstlichen technischen Profilrauigkeiten. Ausgehend von einer allgemeinen Darstellung des Wärmeüberganges werden schrittweise die Modellgleichungen hergeleitet. Die Darstellung berechneter Verläufe gegenüber Messwerten zeigt eine gute Übereinstimmung der Ergebnisse.
Anwendung hydrodynamisch erzeugter „Superkavitation”︁ in der Belüftungstechnik
Authors: Schmid A.
Published: March 2007

Ein neu entwickeltes System zur feinblasigen Belüftung durch Lufteintrag bei „Superkavitation”︁ ist deutlich leistungsfähiger als herkömmliche bekannte Belüfter auf Basis des Strahlpumpenprinzips und vergleichbar mit Sauerstoffeintragswerten von Membran‐ und Folienplattenbelüftern. Der eingebaute Prototyp (Superkavitationsbelüfter) in einer Kläranlage weist einen um ca. 1/3 geringeren Lufteintrag im Gegensatz zum substituierten Strahlpumpensystem auf. Trotz dieser geringeren Lufteintragsleistung reduzierte sich der tägliche Reinsauerstoffbedarf des zusätzlich installierten Membranbelüftungssystems um ca. 49 % und dies über einen Versuchszeitraum von mehr als sieben Monaten. Durch Einsatz dieses neuen Belüfters konnten bereits während der ersten Versuchsphase von drei Monaten mehr als 10 000 € durch Reduzierung des Reinsauerstoffbedarfs eingespart werden.
Mathematical solution of the problem of roll‐waves in inclined opel channels
Authors: Dressler Robert F.
Published: March 2007

The purpose of this paper is to obtain solutions which are periodic with respect to distance, describing the phenomenon called “roll‐waves,” for water flow along a wide inclined channel, and to discuss the behavior of the mathematical solutions. The basic idea presented in Part I is that discontinuous periodic solutions can be constructed by joining together sections of a continuous solution through shocks (or “bores”). It is shown first that no continuous solutions can be periodic and that only one special continuous solution can be used as the basis for constructing discontinuous periodic solutions. The analysis is based upon the non‐linear partial differential equations of the “shallow water theory,” augmented by the Cheay formula to allow for turbulent resistance. The Bresse profile equation is obtained in a form applicable for progressing wave flows. Shock conditions are derived for the case of an arbitrary continuous channel bed and for a flow subject to a resisting force. The special continuous solution is explicitly obtained and analyzed. Branches of it are then joined together through shocks. It is proved that roll‐waves cannot occur either if the resistance is zero or if the resistance exceeds a certain critical value. As the resistance decreases, the size of the waves decreases also; and if the resistance becomes too large, the profiles reverse their direction and can no longer be joined by shocks. This critical value is reached when the (dimensionless) resistance coefficient equals one‐fourth the value of the channel slope. The presence of a resistance force which varies merely with velocity is not sufficient to permit the construction of periodic solutions; the resistance must also act in such a manner that it decreases as the water depth increases. The analysis proves that the ratio of wave height to wave length of roll‐waves is always independent of the speed of the waves. Explicit expressions for water height and shock height as functions of wave length are derived. The investigation studies the static discharge rate as a function of the wave speed, and asymptotic formulas for the wave speed in terms of the average discharge rate are derived. Twelve sets of curves arc presented, based on the equations obtained here, to illustrate the quantitative behavior of roll‐waves; these may be used to check this theory against observed data. For prescribed values of slope, resistance, and wave speed, there is a one‐parameter family of roll‐wave solutions. If the wave length is also prescribed, the solution will then be unique.
New Types of Brönsted Acid–Base Ionic Liquids‐Based Membranes for Applications in PEMFCs
Authors: Fernicola Alessandra , Panero Stefania , Scrosati Bruno , Tamada Masahiro , Ohno Hiroyuki
Published: March 2007

A series of ionic liquids (ILs) are prepared by neutralizing tertiary amines with N,N‐bis(trifluoromethanesulfonyl)imide (HTFSI). As demonstrated by thermal and electrochemical characterizations, these ILs have very good temperature stability and a high ionic conductivity, that is, of the order of 10−2 S cm−1. By incorporating these ILs into a poly(vinylidenfluoride‐co‐hexafluoropropylene) polymer matrix, membranes with a high melting temperature, high decomposition point and with an ionic conductivity of about 10−2 S cm−1 at 140 °C, are obtained. These IL‐based, proton‐conducting membranes are proposed as new polymer electrolytes for high‐temperature polymer electrolyte membrane fuel cells (PEMFCs).
Conflict within the structure of peer mediation: An examination of controlled confrontations in an at‐risk school
Authors: Nix Chris L. , Hale Claudia
Published: March 2007

The purpose of the research reported in this article was to examine the conflict mediation process among middle school students through critical observations and by addressing the disputants' perceptions of their experiences. The interactions and mediations that were observed are examined by the ways in which mediators' adherence to, and deviation from, the mediation script influenced the mediation and the disputants' perceptions of their mediation experience.
My professor is so unfair: Student attitudes and experiences of conflict with faculty
Authors: Harrison Tyler R.
Published: March 2007

A survey of 308 students revealed that student–faculty conflict is widespread, with approximately one‐third of all students reporting a conflict they have pursued. In assessing student knowledge of ombuds processes as an option to resolve conflicts, approximately half of all students had heard of the ombuds office at their institution but had limited understanding of the functions of the office, and virtually none of those surveyed had used the office.