bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term social outcome in children with moyamoya disease who have reached adulthood
Authors: Phi Ji Hoon , Wang Kyu-Chang , Cho Byung-Kyu , Lee Myung Sook , Lee Jong-Hwa , Yu Kyung-Sang , Hahm Bong-Jin , Kim Seung-Ki
Published: September 2011

Object

Although the reported surgical outcome is favorable, there is little information regarding the long-term quality of life in pediatric patients with moyamoya disease (MMD) when they grow to adulthood. The authors conducted a survey to provide details of social adaptation and satisfaction in adults who underwent revascularization surgery for MMD during childhood.

Methods

One hundred twenty-three patients with MMD who had undergone surgery during childhood and were older than 18 years of age were recruited for this study. The authors mailed self-administered questionnaires regarding each patient's education, employment, marriage, driver's license, physical condition, and satisfaction. Sixty-five patients (53%) responded.

Results

Compared with the general population, the patients showed a similar rate of attaining a higher education. Forty-nine (80%) of 61 patients who were not currently high school students had entered college or university. However, the presence of neurological deficits on preoperative examination was a negative predictor of entrance into a college or university, as well as employment. Some patients had difficulty in planning marriage because of physical handicaps, and the rate of acquiring a driver's license and actual driving were relatively low. Approximately 80% of the responders were satisfied with their treatment outcomes, but more than one-half reported subjectively assessed neurological problems.

Conclusions

In this study, pediatric patients with MMD showed favorable social adaptation in adulthood. The findings also indicated that early diagnosis and intervention before the establishment of neurological deficits are essential to children with MMD in becoming better socially adapted. Further, more thorough clinical examinations are required during follow-up in patients with MMD.
Encephalocraniocutaneous lipomatosis: a review of its clinical pathology and neurosurgical indications
Authors: Ayer Robert E. , Zouros Alexander
Published: September 2011

Encephalocraniocutaneous lipomatosis (ECCL) is a rare neurocutaneous syndrome whose hallmark lesions are benign lipomas of the brain and spinal cord. The authors present a case of a male infant with ECCL who had extensive brainstem and spinal cord lipomas. The management of this patient's hydrocephalus, cervicomedullary compression, tethered cord, and scoliosis over the course of his first 2 years of life is described. This case report and review of the literature is presented to provide a synopsis of the problems likely to be encountered by neurosurgeons who treat patients with this syndrome.
A sacral arachnoid cyst causing holocord syringomyelia
Authors: Thakar Sumit , Kiran Narayanam Anantha Sai , Hegde Alangar S.
Published: September 2011

Spinal extradural arachnoid cysts (ACs) have an infrequent predilection for the sacrum. As with their counterparts in other regions of the spine, cysts in this location are mostly asymptomatic. Common presentations in symptomatic cases include pain in the low back or perineum, radiculopathy, and sphincteric dysfunction. The authors report a hitherto undescribed presentation in which the predominant symptoms are those related to an associated holocord syrinx. This 15-year-old boy presented with fluctuating, spastic paraparesis and a dissociated sensory loss in the trunk. Admission MR imaging of the spine showed an extradural AC from S-2 to S-4 and a holocord, nonenhancing syrinx. The patient underwent S-2 laminectomy, fenestration of the cyst, and partial excision of its wall. Intradural exploration revealed a normal-looking filum terminale and the absence of any dural communication with the cyst. At a follow-up visit 6 months after surgery, his motor and sensory deficits had resolved. Follow-up MR imaging showed complete resolution of the syrinx in the absence of the sacral AC. This is the first report of a sacral extradural AC causing holocord syringomyelia. Because conventional theories of syrinx formation were not helpful in elucidating this case, a hypothesis is postulated to explain the clinicoradiological oddity.
Cerebrospinal shunt infection in patients receiving antibiotic-impregnated versus standard shunts
Authors: Parker Scott L. , Anderson William N. , Lilienfeld Sean , Megerian J. Thomas , McGirt Matthew J.
Published: September 2011

Object

Cerebrospinal fluid shunt infections are associated with significant morbidity and mortality in the treatment of adult and pediatric hydrocephalus. Antibiotic-impregnated shunt (AIS) catheters have been used with the aim of reducing shunt infection. While many studies have demonstrated a reduction in shunt infection with AIS, this reported efficacy has varied within the literature.

Methods

The authors performed a systematic literature review to identify all published articles comparing the incidence of CSF shunt infection in AIS versus non-AIS catheters. The incidence of infection for AIS versus non-AIS catheters was calculated using the Mantel-Haenszel common odds ratio, and baseline demographics were compared between AIS and non-AIS cohorts.

Results

Twelve AIS versus non-AIS cohort comparisons were identified in the literature (5 pediatric hydrocephalus, 3 adult hydrocephalus, and 4 mixed populations). In a total of 5613 reported shunt procedures (2664 AISs vs 2949 non-AISs), AISs were associated with a reduction in shunt infection (3.3% vs 7.2%; OR 0.439, p < 0.0001). In 787 shunt procedures for adult hydrocephalus (427 AIS vs 360 non-AIS), AISs were associated with reduction in shunt infection (0.9% vs 5.8%; OR 0.153, p < 0.0001). In 1649 shunt procedures for pediatric hydrocephalus (854 AIS vs 795 non-AIS), AISs were associated with reduction in shunt infection (5.0% vs 11.2%; OR 0.421, p < 0.0001).

Conclusions

The authors' systematic review of the literature demonstrates that AIS catheters are associated with a significant reduction over non-AIS catheters in the reported incidence of CSF shunt infection in adult and pediatric populations. The AIS catheters do not appear to be associated with an increased incidence of antibiotic-resistant microorganisms. Prospective, randomized trials are needed to firmly assess and confirm this apparent difference in infection incidence.
Preliminary Cytotoxicity and Antimicrobial Investigation of Anthocaphalus chinensis
Authors: Hossain M. A. , Sultan M. Z. , Chowdhury A. M. S. , Hasan C. M. , Rashid M. A.
Published: September 2011

The methanol extract of the stem bark of Anthocephalus chinensis as well as its n-hexane, carbon tetrachloride, chloroform and aqueous soluble fractions were subjected to brine shrimp lethality bioassay and microbiological investigation. In the brine shrimp lethality bioassay, the aqueous soluble partitionate of the methanolic extract revealed the highest cytotoxicity having LC50 of 1.19 mg/ml while in case of antimicrobial screening, the chloroform soluble materials demonstrated moderate inhibition of growth of test organisms. Keywords: Anthocephalus chinensis; Rubiaceae; Cytotoxicity; Antimicrobial. © 2011 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved. doi: 10.3329/jsr.v3i3.7529               J. Sci. Res. 3 (3), 689-692 (2011)
Excessive Turbidity Removal from Textile Effluents Using Electrocoagulation Technique
Authors: Islam S. M. N. , Rahman S. H. , Rahman M. M. , Adyel T. M. , Yesman R. A. , Ahmed M. S. , Kaiser N.
Published: September 2011

The work was conducted for improving textile effluent quality via turbidity removal by electrocoagulation (EC) using aluminum sacrificial electrode. Effluents were treated at 30 minutes and 30 volts (30min-30V) and 60 minutes and 40 volts (60min-40V) condition in a 1000 ml reactor cell with anode distance of 4 cm. Prior to EC experiment, physico-chemical parameters of effluent were measured and turbidity level was found eight times higher than the Department of Environment (DoE) standard. Turbidity removal ranged from 53 to 96.2% and 58 to 97.5% for condition one and two, respectively. Dissolved oxygen (DO) increased satisfactorily for both conditions. Total operational cost ranged from 62.50 to 70.41 taka/m3 at 30min-30V and 159.57 to 187.7 taka/m3 at 60min-40V. Moreover, sludge formation ranged from 6.73×10-4 to 8.41×10-4 kg in first condition and 1.21×10-3 to 1.5431×10-3 kg in second one. So, EC treatment was very effective and capable of elevating quality of the textile wastewater effluent in terms of turbidity to discharge into inland surface water. During EC operation it was also possible to lessen the total cost in maximum removal by changing the operating condition and 30min-30V was enough to get environmental friendly solution. Results will encourage the industry-owner to treat polluted effluents by EC.Keywords: Textile industry; ETP; Electrocoagulation; Sacrificial Electrode; Turbidity; Operational cost.© 2011 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved.doi:10.3329/jsr.v3i3.7533               J. Sci. Res. 3 (3), 567-578 (2011)
Analgesic and anti-inflammatory effect of Clausena suffruticosa root extract in animal model
Authors: Rahman M. A. , Chakma J. S. , Islam S. , Rana M. S. , Ahmed N. U.
Published: September 2011

The aim of the study was to evaluate the analgesic and anti-inflammatory effects of Clausena suffruticosa root extract. The effect of different concentrations of ethanolic root extract were studied in animal model using acetic acid induced writhing response, formalin induced pain, hot plate method for analgesic activity in Swiss Albino mice and carrageenan induced paw edema for anti-inflammatory action in Wister Albino rat. The extract reduced writhing response 20% by 0.5g/kg, 57.6% by 1.5g/kg and 78% by 2 g/kg and showed significant analgesic activity as determined by formalin induced pain and hot plate method. In the carrageenan induced paw edema, the extract at a dose of 0.5, 1.0 and 2.0 g/kg showed the highest inhibition 17.23%, 26.30% and 42.46%, respectively, at the 4th hour of administration. The results indicate that the extract shows promising analgesic effect in chemical models of nociception (not related to the opioid system) and anti-inflammatory effect.
Metabolites: A Novel Platform for Converging Research on Metabolism and Metabolomics
Authors: Likić Vladimir A.
Published: September 2011

Technological advances in analytical instrumentation and advances in data modeling are working in synergy to open up new perspectives and research agendas in metabolic research. Thanks to the legacy of the Human Genome Project and its continued impact in the post-genomic era, metabolism is now thought of in a whole-genome context, even when the focus is on a single metabolite and individual metabolic reactions. For a few model organisms we now have extensive, and in some cases complete, information about components that perform integrated metabolic functions. This promises a true paradigm shift in our understanding of the processes of metabolism, but also poses new challenges. As complex and coordinated global behaviors are observed in what were thought to be "simple" organisms, many challenges remain in the experimental domain, as well as in the integration of data generated by increasingly high-throughput analytical techniques. Indeed, in the new era of metabolic research, mathematical and computational modeling is expected to play an increasingly important role. For many complex biochemical phenomena, use of mathematical models may be the best way to build a consistent picture and generate testable hypotheses based on complex yet inevitably incomplete data sets.[...]
Alkylation or Silylation for Analysis of Amino and Non-Amino Organic Acids by GC-MS?
Authors: Villas-Bôas Silas G. , Smart Kathleen F. , Sivakumaran Subathira , Lane Geoffrey A.
Published: September 2011

Gas chromatography–mass spectrometry (GC-MS) is a widely used analytical technique in metabolomics. GC provides the highest resolution of any standard chromatographic separation method, and with modern instrumentation, retention times are very consistent between analyses. Electron impact ionization and fragmentation is generally reproducible between instruments and extensive libraries of spectra are available that enhance the identification of analytes. The major limitation is the restriction to volatile analytes, and hence the requirement to convert many metabolites to volatile derivatives through chemical derivatization. Here we compared the analytical performance of two derivatization techniques, silylation (TMS) and alkylation (MCF), used for the analysis of amino and non-amino organic acids as well as nucleotides in microbial-derived samples. The widely used TMS derivatization method showed poorer reproducibility and instability during chromatographic runs while the MCF derivatives presented better analytical performance. Therefore, alkylation (MCF) derivatization seems to be preferable for the analysis of polyfunctional amines, nucleotides and organic acids in microbial metabolomics studies.
Théorie de l'utilité et mesure des états de santé, le débat QALYs-HYEs
Authors: Le Pen Claude
Published: September 2011

Utility Theory and Health Status measurement: the Debate QALYs vs HYEs

by Claude Le Pen

A vigorous debate has recently opposed int the field on the economic assessment of medical technologies two methods to value health states : the "Quality Adjusted Life Years" (QALYs) and the "Healthy Years Equivalents" (HYEs). For a given health state, the QALYs are defined as the sum of life years allowed in a définie health state, each year being weighted by a coefficient, which reflects the utility of is "quality". The coefficient value varies between 0 and 1, 0 being attached to the worse quality and 1 to the best. This indicator, whose simplicity and intuitive appeal certainly explain the great success, faces nevertheless serious theoretical probems. It can be shown in fact that the preference pattern of an agent who would prefer health state A to health state B if and only if the number of QALYs in A is grater than that in B, obeys a set of restrictive assumptions, so that the psychological profile of the agent lacks credibility. Some authors have thus proposed an alternate measurement, the HYEs, which have the advantage to give an integrated utility measure of both quality and quantity of life, without requiring a complete and restrictive specification of the utility function. More general from a theoretical point of view, this concept proves impossible to be practically implemented. The methods designef to compute empirically the HYEs implicitly require in fact the same limitung assumptions than the QALYs. So, we have from one hand a concept which is easy to implement empirically but without a great theoretical relevance and, from the other hand, a concept which is richer at the theoretical level but is disappointing at the pratical level. Apart from the technical matters, the debate has the interest to reveal the meaning and the limit of the application of utility theory to the measurement of health state.
Une approche hedonique de la formation des prix des médicaments remboursables
Authors: Jacobzonne Stéphane , Martin Edouard , Perrin Vincent , Werle Julien
Published: September 2011

Une approche hédonique de la formation des prix des médicaments remboursables par Stéphane Jacobzone, Edouard Martin, Vincent Perrin et Julien Werle

Une modélisation hédonique permet de formaliser le processus de formation des prix dans le cas du médicament remboursable. Les données utilisées couvrent 24 % du marché français sur la période 1980-1993, permettent de décrire les propriétés physico-chimiques des produits, et ont été appariées avec des données issues d'enquêtes auprès des entreprises. Elles couvrent deux classes thérapeutiques (antiulcéreux et pansements gastro-intestinaux, antihypertenseurs).

La moitié, voire les deux tiers, de la variance des prix en coupe peut être expliquée par les caractéristiques chimiques et pharmacologiques des produits ainsi que par le conditionnement. L'estimation sur données de panel permet d'obtenir des indices de prix hédoniques, en séparant les effets de renouvellement de produits de ceux de déformation du marché. Ces indices ajustés par la qualité évoluent plus rapidement que les indices statistiques officiels, de l'ordre de 20 %. La dynamique des prix est également liée au caractère du produit, innovant ou non. Ce biais, original au niveau international, serait lié aux possibilités de substitutions stratégiques entre produits, au bénéfice de produits plus récents et plus coûteux.
Les équations hédoniques de salaire et la perception subjective des conditions de travail
Authors: Cañada Vicinay Juan A.
Published: September 2011

Les équations de salaire et la perception subjective des conditions de travail :

approche en coupe instantanée sur données françaises

par Juan A. Canada Vicinay

En partant des mauvais résultats des estimations en coupe instantanée des équations hédoniques de salaires, cet article distingue, d'une part, les caractéristiques des emplois selon la manière objective ou subjective dont elles sont perçues par les travailleurs qui les supportent, et d'autre part, introduit les segmentations du marché qui limitent la capacité de la mobilité à régler la compensation des différences. La modélisation de ces deux aspects permet de formuler et de corriger les biais de subjectivité et d'appariement. Le premier considère l'état d'esprit des travailleurs (plus on a un sentiment défavorable envers le travail moins on le supporte et plus on accorde de l'importance aux facteurs gênants et aux aspects insalubres du poste). Le second prend en compte les travailleurs défavorisés, qui supportent en permanence des pénibilités non-compensées par le salaire.
Les tests de racine unitaire et les modèles Arch : application au taux de chômage
Authors: Trabelsi Jamel
Published: September 2011

Les tests de racine unitaire et les modèles Arch : application au taux de chômage

par Jamel Trabelsi

d'informations sur le marché du travail sont prises en compte. Sur la base des conclusions avancées par Kim et Schmidt, selon lesquelles l'hypothèse nulle de racine unitaire est rejetée en présence d'effets Arch sous certaines conditions (processus intégré et dégénéré), nous élaborons une approche économétrique fondée sur les tests de Dickey et Fuller avec des perturbations Garch. Nous montrons que, pour les principaux pays européens, le taux de chômage est persistant. L'existence d'un tel effet pourrait être expliquée par la persistance des chocs de volatilité.
La durée des contrats interentreprises : une analyse empirique
Authors: Saussier Stéphane
Published: September 2011

La durée des contrats interentreprises : une analyse empirique par Stéphane Saussier

Dans cet article, nous étudions la durée des contrats interentreprises en nous plaçant dans le cadre de la théorie des coûts de transaction. Après avoir explicité l'arbitrage à l'uvre dans le choix de la durée des contrats, nous avançons un ensemble de propositions. Nous effectuons un test économétrique sur une base de données non tronquée représentant l'ensemble des relations contractuelles d' une grande entreprise française avec ses fournisseurs sur la période 1 980- 1 995 . Les résultats confortent la théorie des coûts de transaction.
GEMINI-E3, un modèle d'équilibre général national - international économique, énergétique et environnemental
Authors: Bernard Alain , Vielle Marc
Published: September 2011

GEMINI-E3, un modèle d'équilibre général national - international économique, énergétique et

environnemental

par Alain L. Bernard et Marc Vielle

Les trois articles visent à communiquer, d'une manière pédagogique autant que faire se peut, le résultat d'une expérience accumulée de plus de 4 ans. Le premier article, de nature théorique et méthodologique, a pour ambition de présenter le plus simplement possible les mécanismes principaux qui sont enjeu dans ce type de modélisation et qui résultent en particulier des effets de substitution entre biens ou entre facteurs (visés par les politiques économiques concernées), ainsi que des effets liés au commerce international qui s'apparentent plutôt à des effets de revenu (des transferts). Un élément fondamental de l'analyse économique est la mesure du coût des politiques, c'est-à-dire de la perte de bien-être qu'elles occasionnent aux agents économiques qui constituent à la fois la source de l'activité économique et son bénéficiaire privilégié, pour ne pas dire unique, à savoir les consommateurs finals. Les exemples traités, ainsi que les développements théoriques s'appuyant sur des modèles simples, ont pour objet de préciser les concepts de base et de faire apparaître les principaux facteurs qui rendent compte de la nature et de l'importance de ce coût économique.

Le deuxième article présente de manière détaillée la structure du modèle et justifie les choix de modélisation effectués. Le lecteur pourra se rendre compte de la complexité formelle de ce genre de modèle - nécessaire car il faut qu'il soit exhaustif et cohérent - et de sa grande simplicité conceptuelle, puisqu'il s'agit en toute circonstance de décrire des marchés, c'est-à-dire des demandes, des offres, et les mécanismes d'équilibrage par les prix, tout en s'assurant que le circuit des revenus, sous-jacent au fonctionnement de ces marchés, est convenablement bouclé, dans le respect de la loi fondamentale de l'économie attribuée à Walras.

Depuis sa première version de 1995, le modèle a fait l'objet de nombreuses utilisations et de plusieurs communications dans des congrès et séminaires. Ils visent à évaluer des politiques énergétiques soit nationales (le programme électro-nucléaire français), soit régionales ou internationales (la réduction des émissions de gaz à effet de serre). L'application présentée dans le troisième article est de cette dernière nature et vise plus particulièrement à comparer les coûts économiques de différents dispositifs fiscaux permettant d'atteindre un objectif donné de réduction des émissions. Il permet de montrer et surtout de quantifier, dans un cadre national puis européen, combien peut entraîner de surcoûts un mauvais choix des instruments fiscaux.
La contribution du capital public à la productivité des facteurs privés : une estimation sur panel sectoriel pour dix pays de l'OCDE
Authors: Hurlin Christophe
Published: September 2011

La contribution du capital public à la productivité des facteurs privés : une estimation sur panel sectoriel pour dix pays de l'OCDE

par Christophe Hurlin

Dans cet article, nous proposons une estimation des rendements du capital public à partir d'un panel sectoriel de dix pays de l'OCDE. Il ressort de cette étude que, d'une part, l'introduction d'effets spécifiques aux pays ne permet pas de rejeter l'hypothèse de l'existence d'effets productifs significatifs du capital public, mais que, d'autre part, ces effets sont relativement modestes comparés à ceux qui avaient été obtenus à partir d'une spécification en niveau et sur données agrégées chronologiques. Ainsi on n'observe pas d'écart manifeste ou systématique entre les élasticités estimées du capital public et les parts de l'investissement public dans la production.
Impacts de différents instruments de politique agricole en termes de surplus domestique et de relations commerciales
Authors: Richard Vincent
Published: September 2011

Impacts de différents instruments de politique agricole en termes de surplus domestique et de

relations commerciales

par Vincent Richard

Dans le cadre des débats récents sur la prochaine réforme de la PAC et dans la perspective du prochain cycle de négociations commerciales multilatérales, les théories de l'économie du bien-être permettent d'apporter un éclairage sur les enjeux des choix de politiques agricoles en termes de gains de bien-être pour l'ensemble de l'Union européenne. Les conclusions que l'analyse de différentes politiques sous l'angle de l'économie du bien-être permettent de tirer concernent également les relations commerciales.

Il apparaît alors qu'en équilibre partiel sur le secteur agricole, et selon le critère de surplus collectif domestique (somme des gains et des pertes pour les producteurs, les consommateurs et les finances publiques), une économie a intérêt à une suppression multilatérale de toutes les politiques distordant les choix de production et de consommation internes et les échanges commerciaux. Cette voie ne remet pas en cause le respect des objectifs de politique agricole tels ceux assignés à la PAC. Elle permet au contraire de les atteindre au moindre coût, contrairement aux politiques de soutien des prix, assortie ou non de contingentement de l'offre.
Les minima sociaux en France : entre compensation et responsabilité
Authors: Fleurbaey Marc , Hagneré Cyrille , Martinez Michel , Trannoy Alain
Published: September 2011

Les minima sociaux en France : entre compensation et responsabilité par Marc Fleurbaey, Cyrille Hagneré, Michel Martinez et Alain Trannoy

Cet article propose une grille de lecture d'un système de transferts à partir de la notion de responsabilité individuelle : si le montant d'une aide quelconque est indépendant des caractéristiques individuelles des bénéficiaires, ces derniers sont implicitement tenus pour responsables de ces caractéristiques. Après l'exposé du cadre théorique, nous passons en revue l'ensemble des aides destinées aux personnes défavorisées, en examinant successivement la prise en compte de caractéristiques socio-démographiques, et celles des revenus d'activité. Cette approche se révèle utile, en particuUer, pour mettre en lumière des hypothèses implicites un peu bizarres quant aux normes de comportement en matières d'aides inter-individuelles. Un traitement avantageux des familles monoparentales bien que mal adapté semble également émerger. D ' autre part, la prise en compte de la structure dynamique des versements des allocations permet de montrer que la réforme Aubry des minima sociaux a eu un effet non négligeable dans la diminution des trappes à inactivité.
Les hauts revenus face aux modifications des taux marginaux supérieurs de l'impôt sur le revenu en France, 1970-1996
Authors: Piketty Thomas
Published: September 2011

High-Income Taxpayers' Reactions to Marginal Income Tax Rates Changes in France, 1970-1996

by Thomas Piketty

This paper uses the main income tax law changes that occured in France over the 1 970- 1 996 period as " natural experiments " in order to estimate the elasticity of high-income taxpayers' taxable income with respect to marginal tax rates. Given the large pro-cyclicity of the very-high-income taxpayers' income share over the entire period, we use annual tax returns data about the level and composition of income within the top decile and the top centile of the taxpayers distribution of taxable income. The general conclusion is that the relatively large changes in top marginal income tax rates (both in 1981-1982 and 1 986- 1 987) - did not induce any important structural change in the distribution. The distribution of taxable income among high-income taxpayers is extremly stable in France over the entire 1970-1996 period, and short-term fluctuations are better explained by the business cycle than by tax-induced behavioral changes.
Un essai de mesure de la contribution des budgets des pays membres à la cohésion européenne
Authors: Davezies Laurent
Published: September 2011

A Trial Measurement of the Contribution of Member Countries' Budgets to European Cohesion

by Laurent Davezies

This paper presents a preUminary trial measurement, based on a common methodology, of the interregional income transfers resulting from seven European countries' budgets in 1993. A new methodology is proposed, presented and appUed. We find that the national budgets are the main instrument for European interregional cohesion, weU ahead of the Union budget. We also find uneven redistributive effects across the countries studied, which means that European regions with comparable development levels are treated unequally by the pubUc redistributive mechanisms. We conclude with the economic and poUtical implications of this national fragmentation of cohesion mechanisms in Europe.
Synovial Tissue Analysis for the Discovery of Diagnostic and Prognostic Biomarkers in Patients with Early Arthritis: Table 1.
Authors: de HAIR MARIA J.H. , HARTY LEONARD C. , GERLAG DANIELLE M. , PITZALIS COSTANTINO , VEALE DOUGLAS J. , TAK PAUL P.
Published: September 2011

Rheumatoid arthritis (RA) is a chronic disease of unspecified etiology that is manifest by persistent inflammation of the synovium. Considerable efforts have been undertaken globally to study the microenvironment of the inflamed synovium, with many encouraging and enlightening results that bring us closer to unmasking the precise etiologies of RA. Subsequent to these efforts, it has been discovered that CD68-positive macrophages present in abundance in the synovial sublining of the inflamed synovium rescind with treatments that induce clinical improvement in RA. Examination of serial synovial biopsies is now commonly used for screening purposes during early drug development, and the number of centers able to perform synovial tissue biopsy sampling according to standardized methods is increasing.

Having implemented the use of serial synovial tissue biopsies to evaluate the effects of new treatments on the group level in early proof of principle studies, it is the ambition of the OMERACT Synovial Tissue Group to identify synovial diagnostic and prognostic biomarkers that could be used in individual patients. Therefore, we started a prospective study termed the Synoviomics Project aimed at the identification of novel diagnostic and prognostic synovial biomarkers. We will use straightforward and powerful technologies to analyze patient material and assess clinical parameters to identify such biomarkers. These markers may be used in the future to identify patients who are at risk of having persistent and destructive disease and to start tailor-made targeted therapies in an early phase to prevent autonomous disease progression and irreversible joint damage.
Grand âge : Le temps de la re-création
Authors: Dadoun Roger
Published: September 2011

Pour mettre en lumière divers aspects du grand âge, objet courant d’ignorance ou de méconnaissance (le tristement célèbre processus prétendument sénile du « retomber en enfance »), il vaut la peine d’insister sur les capacités créatrices ou re-créatrices de l’enfance comme de la vieillesse. L’espérance de vie qui augmente (à travers de flagrantes inégalités) annonce une ère de centenaires de plus en plus nombreux, en voie de se constituer en fait anthropologique majeur, susceptible d’imprimer un tournant original et imprévisible au mouvement d’une civilisation dont le « malaise » (Freud) confine souvent à la « débâcle » (Péguy).
Repères pour une évaluation de la créativité
Authors: Brun Anne
Published: September 2011

S’il est impossible d’évaluer en soi le taux de créativité d’un sujet, ainsi que de sérier les formes prévisibles de cette créativité, en revanche l’évaluation d’un processus créatif peut être envisagée, au sein d’un atelier à médiation, de façon individuelle ou groupale. L’extension significative ces dernières années des pratiques de soin référées au champ artistique en gérontologie atteste de la portée thérapeutique de ces dispositifs. Il s’agira d’abord de préciser la différence entre créativité et création, afin de définir clairement la visée d’une évaluation de la créativité, puis de différencier, en pratiques institutionnelles, deux types principaux de dispositifs à médiation qui engagent des modalités différentes de créativité, et enfin de proposer quelques repères pour une évaluation de la créativité chez les sujets âgés. Nous verrons que le travail thérapeutique avec des patients souffrant de différentes formes de démence, nécessite de prendre en compte d’autres formes de langage que le langage verbal, à savoir le langage du corps ou le langage sensori-moteur, particulièrement sollicités dans le cadre des médiations thérapeutiques.
Ground‐penetrating radar resolution in cultural heritage applications
Authors: Pérez‐Gracia Vega , González‐Drigo Ramón , Sala Roger
Published: September 2011

High‐resolution methods are required in the non‐destructive study of historical buildings, archaeological sites and cultural heritage structures in general. Ground‐penetrating radar (GPR) is widely used in such studies. However, radar images of archaeological sites and cultural heritage architecture tend to be unclear and are difficult to interpret. Knowledge of the antenna’s behaviour and the optimum expected resolution could help to interpret radar data and define a limit of the real resolution in field surveys. Laboratory tests could provide information about the optimum resolution for each specific antenna. The main goal of this study was to obtain experimental data under lab conditions and thus define the optimum resolution expected in radar surveys. This could then be considered as a limit in field surveys. All of the lab tests were performed using homogeneous media (water and sand) to avoid interference and clutter. As a result, simple images were obtained. The optimum resolution was defined from radar data acquired under these favourable, controlled conditions. In all cases, resolution was defined as the distance (considered as a function of wavelength) between two targets (in the vertical or horizontal axis) that were needed to obtain separate anomalies. All the optimum values were considered to define the limits of the survey resolution in the different cases presented in this paper. In each case, the optimum values were compared with the result and with the radar images to define the best approach to the expected resolution in architectural heritage surveys. To conclude, we define some experimental values of the optimum resolution, described in terms of wavelength. These experimental data are likely to provide a better approach than theoretical estimations.
The shrine of Edward the Confessor: a study in multi‐frequency GPR investigation
Authors: Utsi Erica
Published: September 2011

A series of systematic ground‐penetrating radar (GPR) investigations is being carried out at Westminster Abbey. Following an earlier investigation into the 13th century Cosmati mosaic in the Sanctuary, GPR surveys were commissioned in order to locate the site of a large royal tomb. Antennas of 400 MHz and 4 GHz frequency were used in the area of the High Altar steps and on the floor of the current Shrine Chapel. The investigation uncovered evidence of the target tomb, a number of other graves, some previously unknown and at least one buried object. The paper briefly discusses the frequencies selected, their respective contributions and illustrates how these have resulted in a better understanding of the archaeological and historical evidence.
Cutting Edge: Virus Selectively Primes Human Langerhans Cells for CD70 Expression Promoting CD8+ T Cell Responses
Authors: van der Aar Angelic M. G. , de Groot Rosa , Sanchez-Hernandez Marta , Taanman Esther W. M. , van Lier René A. W. , Teunissen Marcel B. M. , de Jong Esther C. , Kapsenberg Martien L.
Published: September 2011

The two outermost compartments of skin are populated by different Ag-presenting dendritic cell types. Epidermal Langerhans cells (LCs) are evolutionarily adapted to the continuous presence of harmless skin commensals by the selective lack of cell surface TLRs that sense bacteria. In this article, we analyze the ability of LCs and dermal dendritic cells (DDCs) to respond to virus infection. Live virus and intracellular TLR3-agonist dsRNA commit LCs more effectively than DDCs to stimulate naive CD8+ T cell expansion and their differentiation into effector cells. This potent CD8+ T cell-promoting capacity of LCs is causally related to high levels of virus-induced CD70 expression but not to IL-12 production. These data suggest a remarkable specialization of LCs in the induction of pathogen class-specific adaptive immunity. Whereas LCs ignore bacteria, they are superior to DDCs to initiate effective CD70-mediated CD8+ T cells in response to virus stimulation.
Depletion of Autoreactive Plasma Cells and Treatment of Lupus Nephritis in Mice Using CEP-33779, a Novel, Orally Active, Selective Inhibitor of JAK2
Authors: Lu Lily D. , Stump Kristine L. , Wallace Nate H. , Dobrzanski Pawel , Serdikoff Cynthia , Gingrich Diane E. , Dugan Benjamin J. , Angeles Thelma S. , Albom Mark S. , Mason Jennifer L. , Ator Mark A. , Dorsey Bruce D. , Ruggeri Bruce A. , Seavey Matthew M.
Published: September 2011

Accumulating evidence suggests that autoreactive plasma cells play an important role in systemic lupus erythematosus (SLE). In addition, several proinflammatory cytokines promote autoreactive B cell maturation and autoantibody production. Hence, therapeutic targeting of such cytokine pathways using a selective JAK2 inhibitor, CEP-33779 (JAK2 enzyme IC50 = 1.3 nM; JAK3 enzyme IC50/JAK2 enzyme IC50 = 65-fold), was tested in two mouse models of SLE. Age-matched, MRL/lpr or BWF1 mice with established SLE or lupus nephritis, respectively, were treated orally with CEP-33779 at 30 mg/kg (MRL/lpr), 55 mg/kg or 100 mg/kg (MRL/lpr and BWF1). Studies included reference standard, dexamethasone (1.5 mg/kg; MRL/lpr), and cyclophosphamide (50 mg/kg; MRL/lpr and BWF1). Treatment with CEP-33779 extended survival and reduced splenomegaly/lymphomegaly. Several serum cytokines were significantly decreased upon treatment including IL-12, IL-17A, IFN-α, IL-1β, and TNF-α. Anti-nuclear Abs and frequencies of autoantigen-specific, Ab-secreting cells declined upon CEP-33779 treatment. Increased serum complement levels were associated with reduced renal JAK2 activity, histopathology, and spleen CD138+ plasma cells. The selective JAK2 inhibitor CEP-33779 was able to mitigate several immune parameters associated with SLE advancement, including the protection and treatment of mice with lupus nephritis. These data support the possibility of using potent, orally active, small-molecule inhibitors of JAK2 to treat the debilitative disease SLE.
CD134 Plus CD137 Dual Costimulation Induces Eomesodermin in CD4 T Cells To Program Cytotoxic Th1 Differentiation
Authors: Qui Harry Z. , Hagymasi Adam T. , Bandyopadhyay Suman , St. Rose Marie-Clare , Ramanarasimhaiah Raghunath , Ménoret Antoine , Mittler Robert S. , Gordon Scott M. , Reiner Steven L. , Vella Anthony T. , Adler Adam J.
Published: September 2011

Cytotoxic CD4 Th1 cells are emerging as a therapeutically useful T cell lineage that can effectively target tumors, but until now the pathways that govern their differentiation have been poorly understood. We demonstrate that CD134 (OX40) costimulation programs naive self- and virus-reactive CD4 T cells to undergo in vivo differentiation into cytotoxic Th1 effectors. CD137 (4-1BB) costimulation maximized clonal expansion, and IL-2 was necessary for cytotoxic Th1 differentiation. Importantly, the T-box transcription factor Eomesodermin was critical for inducing the cytotoxic marker granzyme B. CD134 plus CD137 dual costimulation also imprinted a cytotoxic phenotype on bystanding CD4 T cells. Thus, to our knowledge, the current study identifies for the first time a specific costimulatory pathway and an intracellular mechanism relying on Eomesodermin that induces both Ag-specific and bystander cytotoxic CD4 Th1 cells. This mechanism might be therapeutically useful because CD134 plus CD137 dual costimulation induced CD4 T cell-dependent tumoricidal function in a mouse melanoma model.
MicroRNA-155 Is Essential for the T Cell-Mediated Control of Helicobacter pylori Infection and for the Induction of Chronic Gastritis and Colitis
Authors: Oertli Mathias , Engler Daniela B. , Kohler Esther , Koch Manuel , Meyer Thomas F. , Müller Anne
Published: September 2011

MicroRNAs govern immune responses to infectious agents, allergens, and autoantigens and function by posttranscriptional repression of their target genes. In this paper, we have addressed the role of microRNA-155 (miR-155) in the control of Helicobacter pylori infection of the gastrointestinal tract and the development of H. pylori-induced chronic gastritis and associated gastric preneoplastic pathology. We show that miR-155 is upregulated in the gastric mucosa of experimentally infected mice and that miR-155−/− mice fail to control H. pylori infection as a result of impaired pathogen-specific Th1 and Th17 responses. miR-155−/− mice are also less well protected against challenge infection after H. pylori-specific vaccination than their wild-type (wt) counterparts. As a consequence of their impaired T cell responses to H. pylori, miR-155−/− mice develop less severe infection-induced immunopathology manifesting as chronic atrophic gastritis, epithelial hyperplasia, and intestinal metaplasia. T cells from miR-155−/− mice that are activated by CD3/CD28 cross-linking expand less and produce less IFN-γ and IL-17 than wt T cells. Finally, we show in this paper using adoptive transfers that the phenotypes of miR-155−/− mice are likely due to T cell-intrinsic defects. In contrast to wt T cells, miR-155−/− T cells from infected donors do not control H. pylori infections in T cell-deficient recipients, do not differentiate into Th1 or Th17 cells, and do not cause immunopathology. In addition, naive miR-155−/− T cells fail to induce chronic Th17-driven colitis in an adoptive transfer model. In conclusion, miR-155 expression is required for the Th17/Th1 differentiation that underlies immunity to H. pylori infection on the one hand and infection-associated immunopathology on the other.
The Joint UK Land Environment Simulator (JULES), model description – Part 1: Energy and water fluxes
Authors: Best M. J. , Pryor M. , Clark D. B. , Rooney G. G. , Essery R .L. H. , Ménard C. B. , Edwards J. M. , Hendry M. A. , Porson A. , Gedney N. , Mercado L. M. , Sitch S. , Blyth E. , Boucher O. , Cox P. M. , Grimmond C. S. B. , Harding R. J.
Published: September 2011

Abstract. This manuscript describes the energy and water components of a new community land surface model called the Joint UK Land Environment Simulator (JULES). This is developed from the Met Office Surface Exchange Scheme (MOSES). It can be used as a stand alone land surface model driven by observed forcing data, or coupled to an atmospheric global circulation model. The JULES model has been coupled to the Met Office Unified Model (UM) and as such provides a unique opportunity for the research community to contribute their research to improve both world-leading operational weather forecasting and climate change prediction systems. In addition JULES, and its forerunner MOSES, have been the basis for a number of very high-profile papers concerning the land-surface and climate over the last decade. JULES has a modular structure aligned to physical processes, providing the basis for a flexible modelling platform.
Effects of the Change in Cutoff Values for Human Epidermal Growth Factor Receptor 2 Status by Immunohistochemistry and Fluorescence In Situ Hybridization: A Study Comparing Conventional Brightfield Microscopy, Image Analysis-Assisted Microscopy, and Interobserver Variation
Authors: Atkinson Roscoe , Mollerup Jens , Lænkholm Anne-Vibeke , Verardo Mark , Hawes Debra , Commins Deborah , Engvad Birte , Correa Adrian , Ehlers Charlotte Cort , Nielsen Kirsten Vang
Published: September 2011

Context.—New guidelines for HER2 testing have been introduced.

Objectives.—To evaluate the difference in HER2 assessment after introduction of new cutoff levels for both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) and to compare interobserver agreement and time to score between image analysis and conventional microscopy.

Design.—Samples from 150 patients with breast cancer were scored by 7 pathologists using conventional microscopy, with a cutoff of both 10% and 30% IHC-stained cells, and using automated microscopy with image analysis. The IHC results were compared individually and to HER2 status as determined by FISH, using both the approved cutoff of 2.0 and the recently introduced cutoff of 2.2.

Results.—High concordance was found in IHC scoring among the 7 pathologists. The 30% cutoff led to slightly fewer positive IHC observations. Introduction of a FISH equivocal zone affected 4% of the FISH scores. If cutoff for FISH is kept at 2.0, no difference in patient selection is found between the 10% and the 30% IHC cutoff. Among the 150 breast cancer samples, the new 30% IHC and 2.2 FISH cutoff levels resulted in one case without a firm diagnosis because both IHC and FISH were equivocal. Automated microscopy and image analysis-assisted IHC led to significantly better interobserver agreement among the 7 pathologists, with an increase in mean scoring time of only about 30 seconds per slide.

Conclusions.—The change in cutoff levels led to a higher concordance between IHC and FISH, but fewer samples were classified as HER2 positive.
Effect of Heterogeneous Distribution of Monosomy 3 on Prognosis in Uveal Melanoma
Authors: Bronkhorst Inge HG , Maat Willem , Jordanova Ekaterina S , Kroes Wilma GM , Schalij-Delfos Nicoline E , Luyten Gregorius PM , Jager Martine J
Published: September 2011

Context.—Fluorescence in situ hybridization (FISH) analyses on tumor sections and on isolated nuclei showed that even low numbers of cells with monosomy of chromosome 3 adversely affected survival.

Objective.—To determine what percentage of uveal melanoma cells with monosomy of chromosome 3 influences patient mortality.

Design.—To determine the presence of monosomy 3, karyotyping and FISH on cultured cells and FISH on isolated nuclei were performed on 50 primary uveal melanomas. Clinical and pathologic prognostic factors were assessed and compared with 5-year survival data. Analyses were performed using Cox proportional hazards test, log-rank analysis, sensitivity, specificity, and positive and negative likelihood ratios.

Results.—Combined karyotyping and FISH on cultured cells showed monosomy 3 in 19 of 50 cases (38%), whereas determination of the monosomy 3 status by FISH on isolated nuclei with a threshold of 5% assigned 31 of 50 cases (62%) to the monosomy-3 category. When monosomy 3 on isolated nuclei with a cutoff value of 5% was used, a significant difference in 5-year survival was present (hazard ratio, 15.5; P  =  .007), indicating that monosomy 3 in greater than 5% of tumor cells is related to death due to metastases.

Conclusion.—In uveal melanoma, the presence of greater than 5% of cells with monosomy 3, as determined by FISH on isolated nuclei, is associated with the development of metastases within 5 years after enucleation.