2,797 research outputs found
Biosimilars in immune-mediated inflammatory diseases: initial lessons from the first approved biosimilar anti-tumour necrosis factor monoclonal antibody
No full text
To taper or not to taper non biological DMARDs in RA remission?
No full textRemission is now a realistic goal in rheumatoid arthritis (RA), with a third of patients achieving sustained remission through the use of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in modern treat-to-target strategies. Nevertheless, csDMARDs pose a risk of severe side-effects and require regular blood safety monitoring, which is both intrusive for patients and expensive for healthcare systems. This poses a therapeutic challenge – when is it appropriate to withdraw csDMARDs from patients with RA in sustained disease remission?In the first part of this presentation we will use case histories to contrast the possible outcomes following withdrawal of csDMARDs from patients in sustained remission, highlighting the uncertainty facing patients and their clinicians in this scenario (presented by Dr Kenneth Baker). In the second section of this lecture (presented by Prof John Isaacs) we will discuss the criteria to consider when stopping csDMARDs, any potential risks to the strategy, and the potential to identify informative biomarkers to help guide management of the patient in remission
Analysis of Fcγ receptor haplotypes in rheumatoid arthritis: FCGR3A remains a major susceptibility gene at this locus, with an additional contribution from FCGR3B
No full textThe Fcγ receptors play important roles in the initiation and regulation of many immunological and inflammatory processes, and genetic variants (FCGR) have been associated with numerous autoimmune and infectious diseases. The data in rheumatoid arthritis (RA) are conflicting and we previously demonstrated an association between FCGR3A and RA. In view of the close molecular proximity with FCGR2A, FCGR2B and FCGR3B, additional polymorphisms within these genes and FCGR haplotypes were examined to refine the extent of association with RA. Biallelic polymorphisms in FCGR2A, FCGR2B and FCGR3B were examined for association with RA in two well characterized UK Caucasian and North Indian/Pakistani cohorts, in which FCGR3A genotyping had previously been undertaken. Haplotype frequencies and linkage disequilibrium were estimated across the FCGR locus and a model-free analysis was performed to determine association with RA. This was followed by regression analysis, allowing for phase uncertainty, to identify the particular haplotype(s) that influences disease risk. Our results reveal that FCGR2A, FCGR2B and FCGR3B were not associated with RA. The haplotype with the strongest association with RA susceptibility was the FCGR3A–FCGR3B 158V-NA2 haplotype (odds ratio 3.18, 95% confidence interval 1.13–8.92 [P = 0.03] for homozygotes compared with all genotypes). The association was stronger in the presence of nodules (odds ratio 5.03, 95% confidence interval 1.44–17.56; P = 0.01). This haplotype was also more common in North Indian/Pakistani RA patients than in control individuals, but not significantly so. Logistic regression analyses suggested that FCGR3A remained the most significant gene at this locus. The increased association with an FCGR3A–FCGR3B haplotype suggests that other polymorphic variants within FCGR3A or FCGR3B, or in linkage disequilibrium with this haplotype, may additionally contribute to disease pathogenesis
Consideration of Interference Correlation Properties in a JD-CDMA Mobile Radio System with Coherent Receiver Antenna Diversity
No full textIn code division multiple access (CDMA) mobile radio systems, both intersymbol interference and multiple access interference arise which can be combatted by using Joint Detection (JD) techniques, to reduce the degradation in performance resulting from time variance, coherent receiver antenna diversity (CRAD) can be used. The application of JD techniques offers the possibility to exploit the knowledge of noise covariances at the receiver. If only intercell (cochannel) interference is considered, the noise covariances in the uplink receiver of a multiple receiver antenna CDMA mobile radio system depend mainly on the directions of arrival (DOAs) of the interfering signals and the receiver antenna placement. Therefore, if the interferer DOAs are known at the base station, these covariances could be estimated. In this thesis, a realistic model of the uplink of a JD CDMA mobile radio system with CRAD is described in which the above mentioned interference cancelling method is used. Simulation results according to this model are given and evaluated.Applied SciencesElectrical EngineeringTelecommunications and Traffic Control Systems Grou
Dairy farmers’ perceptions toward the implementation of on-farm Johne’s disease prevention and control strategies
No full textmplementation of specific management strategies on dairy farms is currently the most effective way to reduce the prevalence of Johne’s disease (JD), an infectious chronic enteritis of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). However, dairy farmers often fail to implement recommended strategies. The objective of this study was to assess perceptions of farmers participating in a JD prevention and control program toward recommended practices, and explore factors that influence whether or not a farmer adopts risk-reducing measures for MAP transmission. Semi-structured interviews were conducted with 25 dairy farmers enrolled in a voluntary JD control program in Alberta, Canada. Principles of classical grounded theory were used for participant selection, interviewing, and data analysis. Additionally, demographic data and MAP infection status were collected and analyzed using quantitative questionnaires and the JD control program database. Farmers’ perceptions were distinguished according to 2 main categories: first, their belief in the importance of JD, and second, their belief in recommended JD prevention and control strategies. Based on these categories, farmers were classified into 4 groups: proactivists, disillusionists, deniers, and unconcerned. The first 2 groups believed in the importance of JD, and proactivists and unconcerned believed in proposed JD prevention and control measures. Groups that regarded JD as important had better knowledge about best strategies to reduce MAP transmission and had more JD risk assessments conducted on their farm. Although not quantified, it also appeared that these groups had more JD prevention and control practices in place. However, often JD was not perceived as a problem in the herd and generally farmers did not regard JD control as a “hot topic” in communications with their herd veterinarian and other farmers. Recommendations regarding how to communicate with farmers and motivate various groups of farmers according to their specific perceptions were provided to optimize adoption of JD prevention and control measures and thereby increase success of voluntary JD control programs
Knowledge gaps that hamper prevention and control of Mycobacterium avium subspecies paratuberculosis infection
No full textIn the last decades, many regional and country‐wide control programmes for Johne's disease (JD ) were developed due to associated economic losses, or because of a possible association with Crohn's disease. These control programmes were often not successful, partly because management protocols were not followed, including the introduction of infected replacement cattle, because tests to identify infected animals were unreliable, and uptake by farmers was not high enough because of a perceived low return on investment. In the absence of a cure or effective commercial vaccines, control of JD is currently primarily based on herd management strategies to avoid infection of cattle and restrict within‐farm and farm‐to‐farm transmission. Although JD control programmes have been implemented in most developed countries, lessons learned from JD prevention and control programmes are underreported. Also, JD control programmes are typically evaluated in a limited number of herds and the duration of the study is less than 5 year, making it difficult to adequately assess the efficacy of control programmes. In this manuscript, we identify the most important gaps in knowledge hampering JD prevention and control programmes, including vaccination and diagnostics. Secondly, we discuss directions that research should take to address those knowledge gaps
Evaluation of an alternative method of herd classification for infection with paratuberculosis in cattle herds in the United States
No full textObjective - To develop a better system for classification of herd infection status for paratuberculosis (Johne's disease JD]) in US cattle herds on the basis of the risk of potential transmission of Mycobacterium avium subsp paratubeculosis. Sample - Simulated data for herd size and within-herd prevalence; sensitivity and specificity for test methods obtained from consensus-based estimates. Procedures - Interrelationships among variables influencing interpretation and classification of herd infection status for JD were evaluated by use of simulated data for various herd sizes, true within-herd prevalences, and sampling and testing methods. The probability of finding ≥1 infected animal in herds was estimated for various testing methods and sample sizes by use of hypergeometric random sampling. Results - 2 main components were required for the new herd JD classification system: the probability of detection of infection determined on the basis of test results from a sample of animals and the maximum detected number of animals with positive test results. Tables were constructed of the estimated probability of detection of infection, and the maximum number of cattle with positive test results or fecal pools with positive culture results with 95% confidence for classification of herd JD infection status were plotted. Herd risk for JD was categorized on the basis of 95% confidence that the true within-herd prevalence was ≤15%, ≤10%, ≤5%, or ≤2%. Conclusions and Clinical Relevance - Analysis of the findings indicated that a scientifically rigorous and transparent herd classification system for JD in cattle is feasible.Source type: Electronic(1
- …
