Molecular Mechanisms Regulating Human Dendritic Cell Development, Survival and Function

Dendritic cells (DC) are professional antigen presenting cells (APC) with a dual function in the immune system. On the one hand, these specialized leukocytes are equipped to alert the immune system to invading pathogens or other danger signals. On the other, DC can promote tolerogenic responses, a function believed to be of importance to avoid unlimited immune responses or immunity aga

Modern psychometrics applied in rheumatology - a systematic review

Background Although item response theory (IRT) appears to be increasingly used within health care research in general, a comprehensive overview of the frequency and characteristics of IRT analyses within the rheumatic field is lacking. An overview of the use and application of IRT in rheumatology to date may give insight into future research directions and highlight new possibilities for the improvement of outcome assessment in rheumatic conditions. Therefore, this study systematically reviewed the application of IRT to patient-reported and clinical outcome measures in rheumatology. Methods Literature searches in PubMed, Scopus and Web of Science resulted in 99 original English-language articles which used some form of IRT-based analysis of patient-reported or clinical outcome data in patients with a rheumatic condition. Both general study information and IRT-specific information were assessed. Results Most studies used Rasch modeling for developing or evaluating new or existing patient-reported outcomes in rheumatoid arthritis or osteoarthritis patients. Outcomes of principle interest were physical functioning and quality of life. Since the last decade, IRT has also been applied to clinical measures more frequently. IRT was mostly used for evaluating model fit, unidimensionality and differential item functioning, the distribution of items and persons along the underlying scale, and reliability. Less frequently used IRT applications were the evaluation of local independence, the threshold ordering of items, and the measurement precision along the scale. Conclusion IRT applications have markedly increased within rheumatology over the past decades. To date, IRT has primarily been applied to patient-reported outcomes, however, applications to clinical measures are gaining interest. Useful IRT applications not yet widely used within rheumatology include the cross-calibration of instrument scores and the development of computerized adaptive tests which may reduce the measurement burden for both the patient and the clinician. Also, the measurement precision of outcome measures along the scale was only evaluated occasionally. Performed IRT analyses should be adequately explained, justified, and reported. A global consensus about uniform guidelines should be reached concerning the minimum number of assumptions which should be met and best ways of testing these assumptions, in order to stimulate the quality appraisal of performed IRT analyses

Spa treatment for primary fibromyalgia syndrome: a combination of thalassotherapy, exercise and patient education improves symptoms and quality of life

Objectives: To study the effect of a combination of thalassotherapy, exercise and patient education in people with fibromyalgia. -\ud Methods: Patients with fibromyalgia, selected from a rheumatology out-patient department and from members of the Dutch fibromyalgia patient association, were pre-randomized to receive either 2 weeks of treatment in a Tunisian spa resort, including thalassotherapy, supervised exercise and group education (active treatment) or treatment as usual (control treatment). Primary outcome measure was health-related quality of life, measured with the RAND-36 questionnaire. Secondary measures included the Fibromyalgia Impact Questionnaire, the McGill Pain Questionnaire, the Beck Depression Inventory, tender point score and a 6-min treadmill walk test. -\ud Results: Fifty-eight participants receiving the active treatment reported significant improvement on RAND-36 physical and mental component summary scales. For physical health, differences from the 76 controls were statistically significant after 3 months, but not after 6 and 12 months. A similar pattern of temporary improvement was seen in the self-reported secondary measures. Tender point scores and treadmill walk tests improved more after active treatment, but did not reach significant between-group differences, except for walk tests after 12 months. -\ud Conclusions: A combination of thalassotherapy, exercise and patient education may temporarily improve fibromyalgia symptoms and health-related quality of life

Audiovisual cues to uncertainty

This paper presents research on the use of audiovisual prosody to signal a speaker’s level of uncertainty. The first study con-sists of an experiment, in which subjects are asked factual ques-tions in a conversational setting, while they are being filmed. Statistical analyses bring to light that the speakers ’ Feeling-of-Knowing (FOK) correlate significantly with a number of vi-sual and verbal properties. Interestingly, it appears that an-swers tend to have a higher number of marked feature settings (i.e., divergences of the neutral audiovisual expression) when the FOK score is low, while the reverse is true for non-answers. The second study is a perception experiment, in which a selec-tion of the utterances from the first study is presented to sub-jects in one of three conditions: vision only, sound only or vi-sion+sound. Results reveal that human observers can reliably distinguish HighFOK responses from LowFOK responses in all three conditions, be it that answers are easier than non-answers, and that a bimodal presentation of the stimuli is easier than their unimodal counterparts. Results of these two experiments are potentially relevant for improving the communication style in human-machine interaction. 1

Automating Model Comparison in Factor Graphs

Bayesian state and parameter estimation have been automated effectively in the literature, however, this has not yet been the case for model comparison, which therefore still requires error-prone and time-consuming manual derivations. As a result, model comparison is often overlooked and ignored, despite its importance. This paper efficiently automates Bayesian model averaging, selection, and combination by message passing on a Forney-style factor graph with a custom mixture node. Parameter and state inference, and model comparison can then be executed simultaneously using message passing with scale factors. This approach shortens the model design cycle and allows for the straightforward extension to hierarchical and temporal model priors to accommodate for modeling complicated time-varying processes

Hyperuricaemia: a marker of increased cardiovascular risk in rheumatic patients: analysis of the ACT-CVD cohort

Background Gout and hyperuricaemia may be associated with increased cardiovascular risk, but analyses in different populations show conflicting results. This study investigates the impact of serum uric acid, inflammation and traditional CV risk parameters on CV event risk in patients with gouty arthritis and patients with non-gouty rheumatic disease. Methods cross-sectional and prospective multivariate analysis of the relation between tertiles of serum uric acid and individual traditional CV risk factors in a cohort of gouty arthritis (GA, n=172), rheumatoid arthritis (RA, n=480) and osteoarthritis (OA, n=206) patients. Main outcome measures: systolic blood pressure, TC/HDL ratio, GlyHb, BMI and first CV events. Results Individual CV risk factors were significantly less favourable in GA (systolic blood pressure, TC/HDL ratio, BMI, p<0.05). In RA and OA, but not in GA, individual cardiometabolic parameters correlated with serum uric acid values (OA: RA: systolic blood pressure, TC/HDL ratio, BMI; systolic blood pressure, TC/HDL ratio, GlyHb, BMI; p<0.05). In non-GA individuals the highest tertile of serum uric acid (>0.34 mmol/L) and NT proBNP level were independent predictors of first CV events, against age and GlyHb level in GA (p<0.05). The hazard of first CV events was equally significantly increased in GA patients (HR 3.169, 95% CI 1.287-7.806) and non-GA individuals with a serum uric acid ≥ 0.34 mmol/L (HR 3.721, 95% CI 1.603-8.634) compared to non-GA individuals with a serum uric acid < 0.27. Conclusions GA is associated with a 3.1-fold hazard of first CV events. In non-GA rheumatic patients increasing serum uric acid is associated with increased CV risk, whereas CV risk in GA is independent of serum uric acid values. The presence of GA or a baseline serum uric acid in the upper range are possibly stronger predictors of first CV events than some traditional CV risk factors or parameters of inflammatio

Cardiovascular case fatality in rheumatoid arthritis is decreasing; first prospective analysis of a current low disease activity rheumatoid arthritis cohort and review of the literature

Background Previous studies found increased case fatality after myocardial infarction and more frequent sudden death in RA patients compared to non-RA subjects. The RA associated CV risk might be explained by the combined effects of chronic systemic inflammation and increased lifestyle associated cardiovascular risk factors, and modified by the use of medication such as non steroidal anti-inflammatory drugs, corticosteroids and disease modifying anti-rheumatic drugs. Trends in case fatality rate in RA after the introduction of potent anti-inflammatory biologic therapies and treat-to-target treatment strategies aiming at remission are not known. This study was performed to examine the cardiovascular fatality rate in current low disease activity RA, and to evaluate trends in RA associated CV case fatality over time. Methods Prospective study to determine the incidence of fatal and nonfatal CV events in 480 RA patients included in the ACT-CVD cohort between February 2009 and December 2011. Patients with prior CV disease were excluded. Cox regression analysis was performed to determine CV event risk and contributing risk factors over time. The results of the cohort analysis were put into the context of a review of the literature to evaluate trends in RA associated CV fatality rate over time. Results The study included 480 RA patients, 72.3% female with median disease duration of 4.2 years, 72.1% being in clinical remission (Disease Activity Score in 28 joints). During a mean follow up of 2.9 years 29 patients (6%) experienced a first CV event, 2 fatal and 27 non-fatal, corresponding to a 6.9% case fatality rate. Comparison with previous studies in cohorts with successive enrolment periods shows a trend towards a decrease in CV case fatality in RA from 52.9% in 1998 to 6.9% in our study. Conclusion CV case fatality in current low disease activity RA is importantly lower than in previous studies, and a trend towards decreasing CV fatality in RA is suggeste

Essais d'épandage au sol de la deltaméthrine poudre mouillable à différentes doses contre Glossina palpalis (s.l.) dans une zone préforestière de Côte d'Ivoire

Des essais d'épandage au sol de deltaméthrine poudre mouillable 2,5% (NRDC 161) ont été effectués en janvier et novembre 1981 dans le foyer à Trypanosomiase humaine de Bouaflé, Côte d'Ivoire. Ces essais visaient à évaluer l'effet de différentes doses de ce pyréthrinoïde de synthèse sur la densité apparente par piègeage de G. palpalis (s.l.), vecteur de la maladie du sommeil dans la zone concernée. Trois doses ont été testées: 60 g de matière active (g.m.a.) par hectare à la concentration de 0,08% en janvier; 20 et 12 g.m.a./ha en novembre, aux concentrations de 0,027 et 0,016% respectivement. Pour chaque dose donnée, les traitements ont été exécutés une suele fois et à l'aide d'atomiseurs portatifs, Solo Port 423 de 5 m de portée. Les effets immédiats, à court et à moyen terme de l'insecticide sont très satisfaisants qu'il s'agisse des doses de 60 et 20 g.m.a./ha ou de la plus faible dose de 12 g.m.a./ha: taux de réduction de la densité apparente (D.A.P.) du vecteur compris dans l'ensemble entre 90 et 98% durant les deux premiers mois après traitement, quelle que soit la dose. A long terme, des taux de réduction dépassant 95% ont été obtenus jusqu'à 4 mois après épandage même avec la plus faible dose de 12 g.m.a./ha. La plus forte dose de 60 g.m.a./ha ne semble apporter aucun gain appréciable ni dans les taux de mortalité du vecteur, ni dans la rémanence de l'insecticide dans la zone d'étude. Afin de diminuer le cout en insecticide d'une éventuelle campagne de lutte chimique antiglossine et de sauvegarder au mieux les ressources de l'environnement, il est donc recommandé que la deltaméthrine p.m. en épandage au sol et en traitement rémanent, soit utilisée à la dose de 12 g.m.a./h

A branch-point approximant for the equation of state of hard spheres

Using the first seven known virial coefficients and forcing it to possess two branch-point singularities, a new equation of state for the hard-sphere fluid is proposed. This equation of state predicts accurate values of the higher virial coefficients, a radius of convergence smaller than the close-packing value, and it is as accurate as the rescaled virial expansion and better than the Pad\'e [3/3] equations of state. Consequences regarding the convergence properties of the virial series and the use of similar equations of state for hard-core fluids in $d$ dimensions are also pointed out.Comment: 6 pages, 4 tables, 3 figures; v2: enlarged version, extension to other dimensionalities; v3: typos in references correcte

How age and sex affect the erythrocyte sedimentation rate and C-reactive protein in early rheumatoid arthritis

BACKGROUND: The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are two commonly used measures of inflammation in rheumatoid arthritis (RA). As current RA treatment guidelines strongly emphasize early and aggressive treatment aiming at fast remission, optimal measurement of inflammation becomes increasingly important. Dependencies with age, sex, and body mass index have been shown for both inflammatory markers, yet it remains unclear which inflammatory marker is affected least by these effects in patients with early RA. METHODS: Baseline data from 589 patients from the DREAM registry were used for analyses. Associations between the inflammatory markers and age, sex, and BMI were evaluated first using univariate linear regression analyses. Next, it was tested whether these associations were independent of a patient's current disease activity as well as of each other using multiple linear regression analyses with backward elimination. The strengths of the associations were compared using standardized beta (beta) coefficients. The multivariate analyses were repeated after 1 year. RESULTS: At baseline, both the ESR and CRP were univariately associated with age, sex, and BMI, although the association with BMI disappeared in multivariate analyses. ESR and CRP levels significantly increased with age (beta-ESR = 0.017, p < 0.001 and beta-CRP = 0.009, p = 0.006), independent of the number of tender and swollen joints, general health, and sex. For each decade of aging, ESR and CRP levels became 1.19 and 1.09 times higher, respectively. Furthermore, women demonstrated average ESR levels that were 1.22 times higher than that of men (beta = 0.198, p = 0.007), whereas men had 1.20 times higher CRP levels (beta = -0.182, p = 0.048). Effects were strongest on the ESR. BMI became significantly associated with both inflammatory markers after 1 year, showing higher levels with increasing weight. Age continued to be significantly associated, whereas sex remained only associated with the ESR level. CONCLUSIONS: Age and sex are independently associated with the levels of both acute phase reactants in early RA, emphasizing the need to take these external factors into account when interpreting disease activity measures. BMI appears to become more relevant at later stages of the disease