bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping the EQ-5D Index from the SF-12: US General Population Preferences in a Nationally Representative Sample
Authors: Sullivan Patrick W. , Ghushchyan Vahram
Published: July 2006

Background Health status measures provide a numeric score representing a profile of health status across several domains, such as physical and mental health. The SF-12 and its longer form, the SF-36, are examples of generic health status measures. Although these Background. Previous mapping algorithms estimating EQ-5D index scores from the SF-12 were based on preferences from a UK community sample. However, preferences based on the general US population are most appropriate for costeffectiveness analyses done from the societal perspective in the United States. Objective. To provide a mapping algorithm for estimating EQ-5D index scores from the SF-12 based on a nationally representative sample and using preferences based on the general US population.Methods. The Medical Expenditure Panel Survey (MEPS) 2002 and 2000 data were used as independent derivation and validation sets to estimate the relationship between SF-12 scores and EQ-5D index scores, controlling for sociodemographic characteristics and comorbidity burden. Prediction equations for end-users who only have access to SF-12 scores were derived and compared. The empirical performance of censored least absolute deviations (CLAD), Tobit, and ordinary least squares (OLS) analytic methods were compared by calculating the mean prediction error in the validation set.Results. The fully specified CLAD model resulted in the lowest mean prediction error, followed by OLS and Tobit. The CLAD prediction equation based only on SF-12 scores performed better than the fully specified OLS and Tobit models.Conclusion. The current research provides an algorithm for mapping EQ-5D index scores from the SF-12. This algorithm may provide analysts with an avenue to obtain appropriate preference-based health-related quality-of-life scores for use in cost-effectiveness analyses when only SF-12 data are available.
A knowledge acquisition process to analyse operational problems in solid waste management facilities
Authors: Dokas Ioannis M. , Panagiotakopoulos Demetrios C.
Published: July 2006

The available expertise on managing and operating solid waste management (SWM) facilities varies among countries and among types of facilities. Few experts are willing to record their experience, while few researchers systematically investigate the chains of events that could trigger operational failures in a facility; expertise acquisition and dissemination, in SWM, is neither popular nor easy, despite the great need for it. This paper presents a knowledge acquisition process aimed at capturing, codifying and expanding reliable expertise and propagating it to non-experts. The knowledge engineer (KE), the person performing the acquisition, must identify the events (or causes) that could trigger a failure, determine whether a specific event could trigger more than one failure, and establish how various events are related among themselves and how they are linked to specific operational problems. The proposed process, which utilizes logic diagrams (fault trees) widely used in system safety and reliability analyses, was used for the analysis of 24 common landfill operational problems. The acquired knowledge led to the development of a web-based expert system ( Landfill Operation Management Advisor, http://loma.civil.duth.gr), which estimates the occurrence possibility of operational problems, provides advice and suggests solutions.
A model to estimate the methane generation rate constant in sanitary landfills using fuzzy synthetic evaluation
Authors: Garg Anurag , Achari Gopal , Joshi Ramesh C.
Published: July 2006

This paper presents a model using fuzzy synthetic evaluation to estimate the methane generation rate constant, k, for landfills. Four major parameters, precipitation, temperature, waste composition and landfill depth were used as inputs to the model. Whereas, these parameters are known to impact the methane generation, mathematical relationships between them and the methane generation rate constant required to estimate methane generation in landfills, are not known. In addition, the spatial variations of k within a landfill combined with the necessity of site-specific information to estimate its value, makes k one of the most elusive parameters in the accurate prediction of methane generation within a landfill. In this paper, a fuzzy technique was used to develop a model to predict the methane generation rate constant. The model was calibrated and verified using k values from 42 locations. Data from 10 sites were used to calibrate the model and the rest were used to verify it. The model predictions are reasonably accurate. A sensitivity analysis was also conducted to investigate the effect of uncertainty in the input parameters on the generation rate constant.
Injury Admissions to Pediatric Intensive Care Are Predictable and Preventable: A Call to Action
Authors: Joffe Ari R. , Lalani Amina
Published: July 2006

Injuries are often preventable yet remain the most common cause of death in children ages 1 to 19 years in Canada. In this retrospective case series, the authors sought to determine the proportion of injury admissions to a tertiary multidisciplinary university hospital Pediatric intensive care unit (PICU) that were preventable by known measures. Patients were a consecutive sample of 104 children, aged 99 (mean [SD] 70; range, 1-215) months, who were admitted to PICU due to injury from July 1997 to June 1998. Charts were reviewed to determine morbidity (PICU days, ventilation days, and discharge to a rehabilitation hospital), mortality, and whether the injury occurred by a preventable mechanism (as recommended by the American Academy of Pediatrics). Out of 790 admissions, 104 (13.2%) were for injury—81% unintentional and 19% intentional. Unintentional injuries occurred by diverse mechanisms, and 65/84 (77%; 95% confidence interval, 67%-86%) were potentially preventable. Unintentional injuries were especially preventable in the younger age groups ( P= .009): 71% (5/7) in those<1 year; 89% (31/35) in those 1 to 4 years; 89% (16/18) in those 5 to 9 years; and 54% (13/24) in those≥10 years. Most intentional injuries were suicide attempts in adolescents, and 88% had multiple risk factors for suicide. Patients were in PICU for 2.9 (SD 4.5) days, ventilated in 73% for 2.8 (SD 4.4) days, had a mortality of 12.5% (95% confidence interval, 6.8%- 20.4%), and demonstrated common need for rehabilitation. Thus, injuries in children resulting in admission to the PICU are common and highly preventable events with significant morbidity and mortality. Novel strategies to improve the public’s perception of the cost of childhood injury are needed.
Synthesis and Fluorescence Behavior of a Novel p-π Conjugated Graft Polymer
Authors: Qi Xiuxiu , Li Najun , Xu Qingfeng , Lu Jianmei , Wang Lihua
Published: July 2006

The p-< conjugated polyamic acid (PAA) was synthesized by the condensation polymerization of benzoguanamine and pyromellitic dianhydride under microwave irradiation. It was then grafted with a series of toluene-2,4-diisocyanate derivatives with different alkyl chain lengths. The solubility and film-forming capability of the graft PAAs were improved and their emission spectra (PL) were investigated. At the same time, quantum calculation of their molecular oscillator strengths was performed using a single-excitation configuration interaction method. Through these two methods, the effects of the introduction of the graft side chain and the alkyl chain length on the fluorescent behavior were investigated. It was found that the fluorescence intensity of graft polymers were all enhanced according to the length of the alkyl chain. The relationship between fluorescence and molecular structure were compared with the theoretical results.
Professional closure by proxy: the impact of changing educational requirements on class mobility for a cohort of Big 8 partners
Authors: Baskerville Rachel F.
Published: July 2006

Closure events impacting on class mobility may include mechanisms initiated by bodies other than the professional body. The research examines if the introduction of full-time study requirements at universities for aspiring accountants effectively introduced a closure mechanism in the accounting profession. Data was derived from an Oral History study of partners in large firms. The younger partners (born after the Second World War) completed full-time degree study at university, but did not provide evidence of class mobility into the profession. The older cohort, born between 1928 and 1946, completed part-time studies only, few completed a degree, and, in contrast to the younger cohort, shows a perceptible upward movement from lower socio-economic classes into the professional class. This suggests that changing the preferred educational routes for new accountants entering the large chartered accounting (CA) firms compromised the “stepping stone” function of accounting as a portal into the professional class.
Communication Technology and Cultural Politics
Authors: Webb Jen , Schirato Tony
Published: July 2006

The ‘new’ communication technologies occupy a highly contingent place in social consciousness: at once central to our everyday lives, and yet capable of generating anxiety and uncertainty. This article traces some aspects of the relation of everyday people to new media technologies and evaluates the reception and impact of new technologies in their public contexts. Drawing on the thinking of writers such as Slavoj Z izek and Jonathan Crary, we argue that both the fears and celebrations of the media have a considerable lineage. We critically address issues of technological determinism, particularly examining the connection between new media technologies and the politics of global relations.
Interdisciplinary Collaboration and Practice-Based Research
Authors: Leggett Mike
Published: July 2006

Practice-based research and actual collaborative projects between artists and scientists have shown that knowledge about each other's fields, whilst necessary for identifying probable outcomes of mutual benefit, cannot anticipate the emergence of the possible – does knowledge in the form of written papers or experiential artworks emerge from loose collaborations or the highly specified kind? Case studies from early 1970s video through to contemporary digital projects examine collaborations between artists, scientists and technologists and the involvement of audiences with interactive media art that will, between respondent and correspondent, create human computer interaction of a different order, a new aesthetics of interdisciplinary spaces.
Television and Internet Differences by Design
Authors: White Michele
Published: July 2006

The designers and programmers of internet settings may indicate that images and events are distributed in real time and as they happen, the technologies are alive, and that the form is unique, but television and internet sites employ similar narratives about liveness, intimacy, and spatial entrances. Internet renderings of liveness suggest that representations are unmediated because images and texts are presented at the same time as the viewer is watching. This makes the various mediated and constructed aspects of the technologies, including the continuation of normative beliefs about gender, race, and sexuality, easier to ignore. Considering how television structures the viewer, historical and critical writings about television liveness, and narratives about internet liveness, and applying this literature to webcams and other internet settings, indicates that these internet renderings are a part of ongoing cultural conventions and provides methods to resist the more stereotyped aspects of these representations.
The Management of ADHD and Associated Problems in a Young Person with Cleidocranial Dysostosis (CCD) and Mild Intellectual Disability
Authors: McBrien Hamilton , Turk Jeremy , Letch Nicole
Published: July 2006

It is increasingly recognized that comorbidity is common in all fields of psychiatry, and furthermore, it is acknowledged that a large number of individuals with genetically determined conditions have associated behavioural phenotypes, and are more susceptible to particular psychiatric and psychological comorbidities than others. It is also recognized that the identification of such phenotypes enables clinicians to be more aware of the potential difficulties an individual may experience, and hence, facilitate early diagnosis, effective management and prevention, appropriate allocation of resources and psychoeducation for the individual and their family. We describe the case report of a girl with cleidocranial dysostosis (CCD), and comorbid intellectual disability and attention deficit hyperactivity disorder (ADHD), and suggest the possible existence of a behavioural phenotype. We also highlight the lack of an evidence base for the management of ADHD within the learning-disability population, and describe successful management utilizing the current evidence base, which exists for those of average intellectual ability.
Developing a Tier 1 CAMHS Foundation Course: Report on a 4-year Initiative
Authors: Aggett Percy , Boyd Elizabeth , Fletcher John
Published: July 2006

Despite a growing recognition of the strategic importance of the UK's Tier 1 in supporting children and young people with mental health needs, detailed descriptions of the developmental hurdles and content of such courses remain obscure. There are a number of initiatives being undertaken nationally to remedy this and the aim of this article is to contribute the authors’ experience to what is becoming a burgeoning national endeavour. Particular attention is drawn to the problems of developing volume multiagency trainings in areas of significant social deprivation and mental health morbidity but innovation is needed to balance the competing needs for quality, penetration into Tier 1, pressures on staff time and managers’ release constraints. A core syllabus is tentatively suggested, with additional skills components, and a teaching session is explored in detail to illustrate the authors’ methodology and approach.
Application of Computational Fluid Dynamics in Building Design: Aspects and Trends
Authors: Zhai Zhiqiang
Published: July 2006

Computational fluid dynamics (CFD), as the most sophisticated airflow modelling method, can simultaneously predict airflow, heat transfer and contaminant transportation in and around buildings. This paper introduces the roles of CFD in building design, demonstrating its typical application in designing a thermally conformable, healthy and energy-efficient building. The paper discusses the primary challenges of using CFD in the building modelling and design practice. Furthermore, it analyses the developing trends in applying CFD to building design, by thoroughly reviewing the literatures in all the proceedings of the International Conference on Building Simulation, one of the most influential symposiums in the building simulation field.
Formaldehyde and Aromatic Volatile Hydrocarbons in the Indoor Air of Egyptian Office Buildings
Authors: Khoder M. I.
Published: July 2006

Indoor and outdoor measurements of formaldehyde and the aromatic hydrocarbons: benzene, toluene, ethylbenzene, m, p-xylene and o-xylene (BTEX) were conducted at six offices in a suburban area in Giza, Egypt, during the winter 2003-04 season. The mean indoor level of formaldehyde was 59.79ppb in offices where there was no smoking and 85.01ppb in offices where people smoked. The highest mean level of formalde-hyde in offices without smoking was in a new office, 90ppb, and the lowest, 36.16ppb, was in an old office. During the period of study, in 13.33%, 20% and 16.67% of samples from non-smoking, smoking and total offices, respectively, the level of formaldehyde exceeded the ASHRAE standard of 0.1ppm. The mean indoor concentrations of benzene, toluene, ethylbenzene, m, p-xylene and o-xylene were 4.32, 25.06, 3.60, 9.14 and 4.38ppb, respectively, in the six offices. The mean indoor levels in non-smoking offices were lower, and in offices with smoking, higher than the overall mean. The highest mean levels of BTEX in non-smoking offices were found in a new office, whereas the lowest concentrations were recorded in an old office. Significant positive correlations were found between the indoor concentrations of BTEX inside the six offices, except benzene in non-smoking offices. Benzene had only weak positive correlations with these compounds.
From the field phone to the mobile phone: a cultural biography of the telephone in Kibbutz Y
Authors: Ribak Rivka , Rosenthal Michele
Published: July 2006

In 1989, years after the majority of Israeli city dwellers, the members of Kibbutz Y celebrated the installation of telephones in their apartments. We trace the cultural biography of the telephone in Kibbutz Y, with special emphasis upon the practical and symbolic transition from public to private telephones, in order to discuss the role of deliberation in the adoption of new technologies. The biographical approach permits us to discuss parallel developments in the technology, the kibbutz ideology, the society and the interrelationships between them. The article argues that even within a community where ideology is transparent, such as a kibbutz, contradictions and dilemmas inform users’ discourse.
Far-right media on the internet: culture, discourse and power
Authors: Atton Chris
Published: July 2006

This study examines the discourse of the British National Party’s (BNP) website. It explores the site as a form of alternative media, focusing on how it involves members and supporters in its discursive construction of racism. It finds that the discourses and identities produced are played out through a radical reformation of the concepts of power, culture and oppression. Drawing on the post-colonial notion of the Other, the BNP seeks to present itself, its activities and its members as responses to racism and oppression that, it argues, are practised by the Other. While this discourse is constructed through the everyday experiences and attitudes of its members, the hierarchically-determined nature of the site prevents those members from sustained, active involvement in the construction of their own identities. For this reason, the study concludes, the BNP’s site is far from the more open, non-hierarchical practices of ‘progressive’ alternative media.
Appropriating civic information and communication technology: a critical study of Swedish ICT policy visions
Authors: Olsson Tobias
Published: July 2006

With 71 percent of its households owning computers and having internet access, Sweden is one of the world’s leading information and communication technology (ICT) nations. The prevalence of ICT has inspired the Swedish government to ascribe it as a civic tool, capable of cultivating more active citizenship and a stronger democracy. However, despite its lofty intentions, Sweden’s ICT policy has a significant shortcoming: it is uninformed about the everyday lives of citizens. This article aims to shed light on ICT policy through an analysis of the appropriation of the computer and the internet in Swedish working-class households. Specifically, by drawing on semi-structured interviews, observations and media diaries with household respondents, the article critically discusses civic visions in Swedish ICT policy. It concludes with a recontextualizion of the discussion within an international arena.
‘Quality singles’: internet dating and the work of fantasy
Authors: Arvidsson Adam
Published: July 2006

This article builds on a case study of the worldwide online dating site Match.com to develop a theoretical understanding of the place of communication and affect in the information economy. Drawing on theoretical debates, secondary sources, a qualitative survey of dating profiles and an analysis of the features and affordances of the Match.com site, the article argues that internet dating seeks to guide the technologically enhanced communicative and affective capacities of internet users to work in ways so that this produces economically valuable content. This is primarily achieved through branding, which as a technique of governance that seeks to work ‘from below’ and ‘empower’ users to deploy their freedom in certain particular, pre-programmed ways. The argument is that online dating provides a good illustration of how the information economy actively subsumes communicative action as a form of immaterial labour.
Super or superfluous in the South Pacific?
Authors: Fitzsimmons Phil , McKenzie Barbra
Published: July 2006

English

This article discusses the findings of a project that sought to understand the professional, and perhaps the personal, benefits gained from participating in an overseas teaching practicum. Using in-situ classroom observations, semi-structured interviews and informal discussions, it became apparent that the participating students believed they had become empowered because they were forced to take up sets of nested ideals based around personal and professional responsibility. Students thus became much more empowered and confident in both their personal and professional lives.

French

Cet article analyse les conclusions d'un projet de recherche visant à comprendre les avantages professionnels, et peut-être même personnels, procurés par la participation à un stage d'enseignement à l'étranger. D'après les observations faites dans les salles de classe, différentes entrevues semi-structurées et discussions informelles, il apparaît que les élèves participants ont le sentiment que le fait d'être contraints d'adopter des ensembles d'idéaux entremêlés et fondés sur les notions de responsabilité personnelle et professionnelle a renforcé leurs habilités. Après une telle expérience, les élèves se sentent donc beaucoup plus épanouis, compétents et sãrs d'eux dans leur vie personnelle ainsi que dans leur vie professionnelle.

Spanish

En este artículo se exponen los resultados de un proyecto que pretendía analizar las ventajas profesionales, y quizás personales, de realizar prácticas como profesor en el extranjero. Tras realizar observaciones en aulas, entrevistas semiestructuradas y debates informales, se comprobó que los alumnos participantes consideraron la experiencia muy provechosa, ya que se vieron obligados a asumir una serie de ideales basados en la responsabilidad personal y profesional. De este modo, los alumnos se sentían más facultados y seguros tanto en su vida personal como profesional.
International students in English-speaking universities
Authors: Andrade Maureen Snow
Published: July 2006

English

International students in institutions of higher education in English-speaking countries make valuable educational and economic contributions. For these benefits to continue, universities must become more knowledgeable about the adjustment issues these students face and implement appropriate support services. This review identifies factors that influence the adjustment and academic achievement of international students. Adjustment challenges are primarily attributable to English language proficiency and culture. Achievement is affected by English proficiency, academic skills and educational background. Understanding international student adjustment issues has global implications for intercultural education. Successful support interventions are reviewed and implications for practice discussed.

French

Les élèves internationaux étudiant au sein d'institutions d'enseignement supérieur dans des pays anglophones apportent une contribution précieuse tant sur le plan éducationnel que sur le plan économique. Pour continuer à bénéficier de ces atouts, les universités doivent s'informer davantage sur les questions d'adaptation auxquelles ces élèves sont confrontés et mettre en oeuvre des services de soutien appropriés. Cette étude identifie les facteurs qui influencent l'adaptation et les résultats scolaires des élèves internationaux. Les problèmes d'adaptation sont attribués en premier lieu à la maîtrise de la langue anglaise et à la culture. Les résultats scolaires quant à eux sont affectés par la maîtrise de l'anglais, l'aptitude aux études et les acquis scolaires. Comprendre les questions d'adaptation propres aux élèves internationaux a des implications au niveau mondial en termes d'éducation internationale. L'article analyse les interventions de soutien qui portent leurs fruits et discute des implications sur un plan pratique.

Spanish

Los alumnos internacionales de instituciones de enseñanza superior de países angloparlantes realizan valiosas contribuciones educativas y económicas. Para continuar beneficiándose de estas aportaciones, es necesario que las universidades conozcan mejor los problemas de adaptación que afrontan dichos alumnos y pongan en práctica los servicios de apoyo adecuados. En este trabajo se señalan los factores que influyen en la adaptación y el desempeño académico de los alumnos procedentes de otros países. Sus problemas de adaptación se pueden atribuir principalmente a sus conocimientos de la cultura y la lengua inglesa. Su desempeño depende de la competencia lingüística en inglés, las habilidades académicas y la formación educativa. Entender los problemas de adaptación de estos alumnos repercute en la educación intercultural a escala mundial. Asimismo, se examinan iniciativas de apoyo positivas y se analizan sus implicaciones a efectos prácticos.
Diakonia in the New Testament: A Dialogue with John N. Collins
Authors: Gooder Paula
Published: July 2006

The word ministry is widely used, though difficult to define. Within the New Testament, ministry most often translates the Greek word diakonia. For many years scholars were agreed that diakonia meant humble service but the work of John N. Collins has challenged this consensus. This paper seeks to evaluate Collins’s work and to ask what his study contributes to an understanding of ‘ministry’ within the church. Its conclusions are that there are no substantial problems with Collins’s interpretation of diakonia and its cognates. Most occurrences of the word are better understood to mean ‘the carrying out of a commissioned task’ than the more traditional ‘humble service’. This can offer some helpful insights into the meaning and shaping of ministry within the church today.
Getting causal considerations back on the right track
Authors: Höfler Michael
Published: July 2006

In their commentary on my paper Phillips and Goodman suggested that counterfactual causality and considerations on causality like those by Bradford Hill are only "guideposts on the road to common sense". I argue that if common sense is understood to mean views that the vast majority of researchers share, Hill's considerations did not lead to common sense in the past – precisely because they are so controversial. If common sense is taken to mean beliefs that are true, then Hill's considerations can only lead to common sense in the simple and well-understood causal systems they apply to. Counterfactuals, however, are largely common sense in the latter meaning.

I suggest that the road of scientific endeavour should lead epidemiologic research toward sound strategies that equip researchers with skills to separate causal from non-causal associations with minimal error probabilities. This is undeniably the right direction and the one counterfactual causality leads to. Hill's considerations are merely heuristics with which epidemiologists may or may not find this direction, and they are likely to fail in complex landscapes (causal systems). In such environments, one might easily lose orientation without further aids (e.g., defendable assumptions on biases). Counterfactual causality tells us when and how to apply these heuristics.
Activation of sterol regulatory element-binding proteins (SREBPs) is critical in IL-8-induced angiogenesis
Authors: Yao Min , Zhou Rui-Hai , Petreaca Melissa , Zheng Lei , Shyy John , Martins-Green Manuela
Published: July 2006

Angiogenesis is essential in many physiological and pathological processes and can be stimulated by many different fators. To better understand and to manipulate this process more effectively, it would be beneficial to identify molecules common to the signaling pathways stimulated by different classes of angiogenic factors. Sterol regulatory element-binding proteins (SREBPs) are involved in the metabolism of cholesterol and fatty acids, molecules that are critical in membrane biology, and hence, many of the processes involved in angiogenesis. Here, we show that angiogenic factors of different families, such as basic fibroblast growth factor, thrombin, and interleukin (IL)-8, stimulate SREBP activation, whereas nonangiogenic factors, such as transforming growth factor-β1, do not. We focused our detailed studies on IL-8 in vitro and in vivo, as this chemokine is also involved in inflammation and hence, has the potential to be critical in inflammation-induced angiogenesis, a process common to many diseases. Using human microvascular endothelial cells, a rabbit skin wound-healing model, and the chorioallantoic membrane assay, we show that IL-8 stimulates the activation of SREBP-1 and -2, and this activation is specific and receptor-mediated. SREBP activation leads to activation of RhoA through 3-hydroxy-3-methylglutaryl CoA reductase. RhoA is a small guanosinetriphosphatase, important in cytoskeletal functions, which in turn, are critical in many of the cellular processes needed for angiogenesis. Given that diverse, angiogenic factors use different cell-surface receptors, identification of this common step in the signal-transduction pathway provides the opportunity for novel approaches for prevention and treatment of diseases involving abnormal angiogenesis.
The Physiology of Human Glucocorticoid Receptor β (hGRβ) and Glucocorticoid Resistance
Authors: LEWIS‐TUFFIN LAURA J. , CIDLOWSKI JOHN A.
Published: July 2006

Abstract: The development of glucocorticoid (GC) resistance is a serious problem that complicates the treatment of immune‐related diseases, such as asthma, ulcerative colitis, and hematologic cancers. hGRα and hGRβ are two isoforms of the human glucocorticoid receptor, which differ in the structural composition of the carboxy‐terminal end of the ligand‐binding domain and therefore in their ability to bind glucocorticoid ligand and in their physiological function. hGRα is the classically functional GR, while hGRβ seems to act mainly as a dominant negative to the function of hGRα. Because of the ability of hGRβ to antagonize the action of hGRα, it has been hypothesized that changes in the expression of hGRβ may underlie the development of glucocorticoid resistance. In this article we review what is known about the expression and physiological action of hGRβ in normal cells and tissue as well as in several disease states. Taken together, the evidence suggests that the ratio of hGRα:hGRβ expression is indeed critical to the glucocorticoid responsiveness of various cells. This ratio can be altered by changing the expression level of hGRα, hGRβ, or both receptors simultaneously. Higher ratios correlate with glucocorticoid sensitivity, while lower ratios correlate with glucocorticoid resistance. Thus hGRβ can be an important modulator of glucocorticoid responsiveness.
Angiotensin‐Converting Enzyme in Systemic Sclerosis
Authors: GUIDUCCI SERENA , FATINI CINZIA , ROGAI VERONICA , CINELLI MARINA , STICCHI ELENA , ABBATE ROSANNA , CERINIC MARCO MATUCCI
Published: July 2006

Abstract: The main pathologic hallmark of systemic sclerosis (SSc) is endothelial derangement; the pathologic alterations of the vessel wall in SSc are strikingly similar to the modification detected in the atherosclerotic lesions, and it is now evident that SSc is also characterized by accelerated macrovascular disease. Peptides related to angiotensin II, the final product of the renin–angiotensin system (RAS), play a role as regulators of endothelial cell function. Angiotensin‐converting enzyme (ACE), the key enzyme in the RAS, is the predominant pathway of angiotensin II formation in blood and tissues. In intron 16 of the gene encoding for ACE an insertion/deletion (I/D) polymorphism, consisting of the presence or absence of a 287–base pair Alu sequence, has been identified. This polymorphism has been related to ACE enzyme levels, and data from experimental studies reported a functional role for this polymorphism in modulating the angiotensin II levels. We previously documented a high ACE D allele frequency in SSc patients and its role in increasing the risk of SSc, thus suggesting that the I/D polymorphism might be a useful genetic marker to identify SSc patients at risk to develop a severe vascular disease, frequently leading to gangrene. Moreover, our preliminary data, besides supporting the role of ACE I/D polymorphism as a predisposing factor to SSc, demonstrated its involvement in accelerated macrovascular disease by increasing the intima media thickness. Therefore, in SSc, not only endothelial dysfunction, but also vascular damage, linked to ACE I/D polymorphism, may significantly contribute to accelerated macrovascular disease, as the ACE D allele, by regulating both the production of angiotensin II and the degradation of bradykinin, contributes to mechanisms involved in the induction and maintenance of vessel wall modification.
Genetic Variation in the Endothelin System
Authors: ROSSI GIAN PAOLO , PITTER GISELLA
Published: July 2006

Abstract: Endothelin‐1 (ET‐1) exerts multiple biological effects, including vasoconstriction and the stimulation of cell proliferation in tissues both within and outside of the cardiovascular system. ET‐1 is synthesized by ET‐converting enzymes (ECE), chymases (CMAs), and non‐ECE metalloproteases through a process regulated in an autocrine fashion in vascular and nonvascular cells. ET‐1 acts through the activation of Giprotein–coupled receptors. ETAreceptors mediate vasoconstriction and cell proliferation, whereas ETBreceptors are important for aldosterone secretion, endothelial cell (EC) migration, the release of nitric oxide (NO) and prostacyclin, the clearance of ET‐1, and the inhibition ofECE‐1. ET is activated in scleroderma, hypertension, atherosclerosis, restenosis, heart failure, idiopathic cardiomyopathy, and renal failure. Tissue concentrations more reliably reflect the activation of the ET system because of the predominantly abluminal secretion of the peptide. Experimental studies and clinical trials have demonstrated that ET‐1 plays a major role in normal cardiovascular homeostasis and in the functional and structural changes observed in arterial and pulmonary hypertension, glomerulosclerosis, atherosclerosis, and heart failure. Accordingly, ET antagonists are promising new agents in the treatment of cardiovascular diseases. Single nucleotide polymorphisms (SNPs) of the genes ofpreproET‐1,ECE‐1, CMA, ETAand ETBreceptors have been identified and can be important for their functional regulation. However, for most of them the association with disease conditions and the evidence for a functional role remain controversial. Thus, even though ET antagonists are being used for the treatment of pulmonary hypertension, there is no convincing evidence for a role of SNPs in affecting the therapeutic strategies.
The Impact of Stressors on Health Status and Hypothalamic‐Pituitary‐Adrenal Axis and Autonomic Nervous System Responsiveness in Rheumatoid Arthritis
Authors: GEENEN RINIE , VAN MIDDENDORP HENRIËT , BIJLSMA JOHANNES W.J.
Published: July 2006

Abstract:  The hypothalamic‐pituitary‐adrenal (HPA) axis and the autonomic nervous system (ANS) are critically involved in inflammation and are activated by stress. This suggests that stressful circumstances may affect the chronic inflammation of rheumatoid arthritis (RA). Fifty‐six scientific publications of the past 15 years were reviewed to get insight into the possible impact of stressors (grouped in five categories) on the health status and HPA axis and ANS functioning of adult patients with RA. Our findings in this review were: (1) In response to mental and physical effort and applied physiological stressors, patients demonstrate ANS hyporesponsiveness and “too normal” HPA axis responsiveness considering the elevated immune activity. A premorbid defect, past and current inflammatory activity, past and current stress, and physical deconditioning may explain disturbed physiological responses. (2) After brief naturalistic stressors, self‐perceived and clinician's ratings of disease activity are increased; inflammation parameters have been insufficiently examined. (3) Major life events do not univocally affect disease status, but appear able to modify disease activity in a positive or negative way, depending on the nature, duration, and dose of the accompanying physiological stress response. (4) Enduring (e.g., work‐related or interpersonal) stressors are associated with perceived health. Because this stressor category mingles with personality variables, the mere observation of a correlation does not prove that chronic stressors provoke health changes, although this might be the case. (5) Not one study rigorously examined the prospective hypothesis that past stressors (e.g., childhood victimization or pre‐onset stressful incidents) may trigger RA or aggravate existing RA, which is a realistic belief for some patients.
Increased Neural Sympathetic Activation in Fibromyalgia Syndrome
Authors: SARZI‐PUTTINI PIERCARLO , ATZENI FABIOLA , DIANA ALESSANDRO , DORIA ANDREA , FURLAN RAFFAELLO
Published: July 2006

Abstract:  Fibromyalgia (FM) is a syndrome characterized by widespread musculoskeletal pain, although the mechanisms underlying the pain have not been fully elucidated. FM patients describe a number of nonspecific symptoms, such as anxiety, depression, fatigue, unrefreshing sleep, and gastrointestinal complaints, which appear after a flu‐like illness, or after physical or emotional trauma in half of the patients, and are often exacerbated by exertion, stress, lack of sleep, and weather changes. There may also be symptoms of orthostatic intolerance, which suggests underlying abnormalities in cardiovascular neural regulation. Research suggests that various components of the central nervous system are involved, including the hypothalamic‐pituitary‐adrenal (HPA) axis, pain‐processing pathways, and the autonomic nervous system (ANS). This review discusses the general aspects of the altered HPA and ANS, sympathetic overactivity, and alterations in cardiovascular autonomic responses to gravitational stimuli.
Innervation of the Joint and Role of Neuropeptides
Authors: KONTTINEN YRJÖ T. , TIAINEN VELI‐MATTI , GOMEZ‐BARRENA ENRIQUE , HUKKANEN MIKA , SALO JARI
Published: July 2006

Abstract:  Rheumatoid arthritis is considered to represent a disease of the synovial membrane, osteoarthritis of the hyaline articular cartilage, and osteoporosis of the bone. It can be questioned to what extent this is true and to what extent these diseases could be considered to be due to extra‐articular, extra‐skeletal pathology related to the neuroendocrine system. Pain is the main symptom in arthritis. This is related to prostaglandin‐mediated sensitization of the primary afferent nociceptive nerves. Accordingly, nonsteroidal anti‐inflammatory drugs are used in symptomatic treatment, occasionally together with opioids and tricyclic antidepressants. The midline symmetry and involvement of the richly innervated, small peripheral joints in rheumatoid arthritis have raised speculation about the role of neurogenic inflammation and neuropeptides in its pathogenesis. In contrast to the free nerve endings, the role of the proprioceptive sensors is to provide information of our actual motor performance (the afferent copy of our movements) compared to the efferent motor program, which is activated by our will to move. These include proprioceptors in the skin (e.g., Meissner corpuscles), muscles (annulospiral and flower‐spray endings of the muscle spindles), Golgi tendon organs, and Ruffini end organs and Pacinian corpuscles in the superficial and deep layers of the joint capsule. Elderly people may have slow reflexes, lax joints, joint incongruity, and loss of muscle power; obesity, alcohol and medicinal use, and joint pain can be combined with poor/nonexisting capacity for repair and remodeling of the musculoskeletal tissues. Impaired biomechanics contributes to increased joint tenderness, accumulation of minor trauma (secondary osteoarthritis), and falls (osteoporotic fractures). More attention needs to be paid to aging of proprioception, not only to the terminal disease target.
Inflammation and Sex Hormone Metabolism
Authors: SCHMIDT MARTIN , NAUMANN HEIDRUN , WEIDLER CLAUDIA , SCHELLENBERG MARTINA , ANDERS SVEN , STRAUB RAINER H.
Published: July 2006

Abstract:  The incidence of autoimmune diseases is higher in females than in males. In both sexes, adrenal hormones, that is, glucocorticoids, dehydroepiandrosterone (DHEA), and androgens, are inadequately low in patients when compared to healthy controls. Hormonally active androgens are anti‐inflammatory, whereas estrogens are pro‐inflammatory. Therefore, the mechanisms responsible for the alterations of steroid profiles in inflammation are of major interest. The local metabolism of androgens and estrogens may determine whether a given steroid profile found in a subject's blood results in suppression or promotion of inflammation. The steroid metabolism in mixed synovial cells, fibroblasts, macrophages, and monocytes was assessed. Major focus was on cells from patients with rheumatoid arthritis (RA), while cells from patients with osteoarthritis served as controls. Enzymes directly or indirectly involved in local sex steroid metabolism in RA are: DHEA‐sulfatase, 3β‐hydroxysteroid dehydrogenase, 17β‐hydroxysteroid dehydrogenase, and aromatase (CYP19), which are required for the synthesis of sex steroids from precursors, 5α‐reductase and 16α‐hydroxylase, which can be involved either in the generation of more active steroids or in the pathways leading to depletion of active hormones, and 3α‐reductase and 7α‐hydroxylase (CYP7B), which unidirectionally are involved in the depletion of active hormones. Androgens inhibit aromatization in synovial cells when their concentration is sufficiently high. As large amounts of estrogens are formed in synovial tissue, there may be a relative lack of androgens. Production of 5α‐reduced androgens should increase the local anti‐inflammatory activity; however, it also opens a pathway for the inactivation of androgens. The data discussed here suggest that therapy of RA patients may benefit from the use of nonaromatizable androgens and/or the use of aromatase inhibitors.
Circadian Rhythms
Authors: CUTOLO MAURIZIO , SULLI ALBERTO , PIZZORNI CARMEN , SECCHI MARIA ELENA , SOLDANO STEFANO , SERIOLO BRUNO , STRAUB RAINER H. , OTSA KATI , MAESTRONI GEORGES J.
Published: July 2006

Abstract:  Circadian rhythms are driven by biological clocks and are endogenous in origin. Therefore, circadian changes in the metabolism or secretion of endogenous glucocorticoids are certainly responsible in part for the time‐dependent changes observed in the inflammatory response and arthritis. More recently, melatonin (MLT), another circadian hormone that is the secretory product of the pineal gland, has been found implicated in the time‐dependent inflammatory reaction with effects opposite those of cortisol. Interestingly, cortisol and MLT show an opposite response to the light. The light conditions in the early morning have a strong impact on the morning cortisol peak, whereas MLT is synthesized in a strictly nocturnal pattern. Recently, a diurnal rhythmicity in healthy humans between cellular (Th1 type) or humoral (Th2 type) immune responses has been found and related to immunomodulatory actions of cortisol and MLT. The interferon (IFN)‐γ/interleukin (IL)‐10 ratio peaked during the early morning and correlated negatively with plasma cortisol and positively with plasma MLT. Accordingly, the intensity of the arthritic pain varies consistently as a function of the hour of the day: pain is greater after waking up in the morning than in the afternoon or evening. The reduced cortisol and adrenal androgen secretion, observed during testing in rheumatoid arthritis (RA) patients not treated with glucocoticoids, should be clearly considered as a “relative adrenal insufficiency” in the presence of a sustained inflammatory process, and allows Th1 type cytokines to be produced in higher amounts during the late night. In conclusion, the right timing (early morning) for the glucocorticoid therapy in arthritis is fundamental and well justified by the circadian rhythms of the inflammatory mechanisms.
Is the Course of Steroid‐Treated Polymyalgia Rheumatica More Severe in Women?
Authors: CIMMINO MARCO A. , PARODI MASSIMILIANO , CAPORALI ROBERTO , MONTECUCCO CARLOMAURIZIO
Published: July 2006

Abstract:  Polymyalgia rheumatica (PMR) has a marked preponderance in women. The female sex has been claimed to be a risk factor for longer‐course corticosteroid therapy and to be associated with more severe systemic symptoms and lower hemoglobin levels. Eighty consecutive patients affected by PMR, seen at two tertiary referral centers, were followed‐up for a mean period of 14.9 months after initiating corticosteroid treatment. At presentation, women had longer disease duration and lower hemoglobin levels (both P= 0.05) than men. In contrast, their systemic signs of PMR were less common (P= 0.01). Women were treated with a slightly higher mean daily dose of prednisone (P= 0.055), and assumed a significantly higher cumulative dosage of the drug (P= 0.01). Accordingly, the mean number of steroid‐related side effects was higher among women (P= 0.003). The number of relapses during steroid treatment (P= 0.02), but not that of recurrences, was increased in women. ESR, which was raised at presentation, significantly declined during follow‐up to normal values in both subgroups (P < 0.00001 by analysis of variance [ANOVA]). Its decrease was significantly more pronounced in men than in women. Hemoglobin at follow‐up was significantly higher in men than in women at any given time point. In conclusion, sex is probably modulating the response to corticosteroids. This finding emphasizes the need to consider differences between males and females in the clinical and therapeutic approach to PMR patients.
Predicting and Preventing Autoimmunity, Myth or Reality?
Authors: HAREL MICHAL , SHOENFELD YEHUDA
Published: July 2006

Abstract:  Many autoimmune diseases are chronic conditions that progress over the course of years, and are characterized by the presence of autoantibodies that precede the overt disease by months or years. As examples, the presence of two islet cell antibodies (ICA) are associated with a 50% risk of developing diabetes mellitus in 5 years, anticyclic citrullinated (anti‐CCP) antibodies are found in the sera of rheumatoid arthritis (RA) patients a median of 4.5 years before the overt disease, and in systemic lupus erythematosus (SLE), patients accrue antibodies throughout a foreseen course during the 3–4 years prior to the clinical symptoms. This ability to predict autoimmune diseases, or rather their clinical manifestations, leads to the prospect of screening healthy individuals for autoantibodies. The importance of such a notion lies not only in the ability to prevent life‐threatening manifestations, such as Addisonian's crisis and thyroid storm, but also in the ability to treat and even prevent overt autoimmune diseases. Among such documented treatment modalities are administration of aspirin in antiphospholipid syndrome, ursodeoxycholic acid in primary biliary cirrhosis (PBC), vitamin D in SLE and autoimmune thyroid diseases (AITD), and more. Although additional studies are still needed to fully assess these notions, as well as the appropriate screening strategies to apply them, one cannot ignore the prospect of predicting and preventing autoimmunity.