2,644 research outputs found
Clinical phenotypes in bronchiectasis: right on track to develop precision medicine in respiratory diseases
Consideration of Interference Correlation Properties in a JD-CDMA Mobile Radio System with Coherent Receiver Antenna Diversity
In 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
Association study of mannose-binding lectin levels and genetic variants in lectin pathway proteins with susceptibility to age-related macular degeneration: A case-control study
BACKGROUND: In age-related macular degeneration (AMD) the complement system is thought to be activated by chronic oxidative damage with genetic variants identified in the alternative pathway as susceptibility factors. However, the involvement of the lectin pathway of complement, a key mediator of oxidative damage, is controversial. This study investigated whether mannose-binding lectin (MBL) levels and genetic variants in lectin pathway proteins, are associated with the predisposition to and severity of AMD. METHODS: MBL levels and single nucleotide polymorphisms (SNPs) in the MBL2 and the ficolin-2 (FCN2) gene were determined in 109 patients with AMD and 109 age- and sex-matched controls. RESULTS: MBL expression levels were equally distributed in both cases (early and late AMD) and controls (p>0.05). However, there was a trend towards higher median MBL levels in cases with late AMD compared to cases with early AMD (1.0 vs. 0.4 μg/ml, p = 0.09) and MBL deficiency (0.05 for all analyses) as were MBL2 genotypes. Similarly, there was no significant difference in allele frequencies in any SNPs in either the MBL2 or FCN2 gene in cases with early vs. late AMD. CONCLUSIONS: SNPs of lectin pathway proteins investigated in this study were not associated with AMD or AMD severity. However, MBL levels deserve further study in a larger cohort of early vs. late AMD patients to elucidate any real effect on AMD severity
Dairy farmers’ perceptions toward the implementation of on-farm Johne’s disease prevention and control strategies
mplementation 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
IDEOLOGICALLY CHALLENGING ENTERTAINMENT (ICE)
Ideologically Challenging Entertainment (ICE) is entertainment that challenges ‘us vs. them’ ideologies associated with radicalization, violent conflict and terrorism. ICE presents multiple perspectives on a conflict through mainstream entertainment. This article introduces the theoretical underpinnings of ICE, the first ICE production and the audience responses to it.
The first ICE production was Two Merchants: The Merchant of Venice adapted to challenge ideologies of the Arab-Israeli Conflict. A mixed-methods study of audience responses explored whether this production inspired audiences to shift their ideological views. Each performance included two versions of the adaptation: a Jewish dominated society with an Arab Muslim minority, contrasted with an Arab Muslim dominated society and a Jewish minority. A mixed-methods study of audience responses explored whether this production inspired audiences to shift their ideological views to become more tolerant of differences away from ideological radicalization.
Of audience members who did not initially agree with the premise of the production, 40% reconsidered their ideological views, indicating increased tolerance, greater awareness of and desire to change their own prejudices. In addition, 86% of the audience expressed their intention to discuss the production with others, thereby encouraging critical engagement with, and broader dissemination of the message. These outcomes suggest that high quality entertainment – as defined by audience responses to it - can become a powerful tool in the struggle against radicalised ideologies
Lectin pathway of complement and bacterial colonisation in bronchiectasis
Bronchiectasis is a chronic inflammatory lung disease associated with failure of the
normal mucociliary escalator, chronic bacterial colonisation of the airways,
neutrophil mediated inflammation and a resulting clinical syndrome of respiratory
infections, lung damage and symptoms such as cough, sputum production and
shortness of breath. These are few effective treatments and the cause of
bronchiectasis is unknown in the majority of patients. It is hypothesised that
unrecognised immune defects may predispose to bronchiectasis or affect the severity
of lung disease.
Ficolin-2 is a circulating innate immune protein able to activate the lectin pathway of
complement through interaction with mannose binding lectin associated serine
protease-2. Through its structural and functional similarity to complement
component C1q and mannose binding lectin, it is hypothesised that ficolin-2 may be
involved in opsonophagocytosis of pathogens. A number of single nucleotide
polymorphisms in the ficolin-2 gene have been described causing considerable
variation in human ficolin-2 serum concentrations in healthy individuals.
In this thesis, the role of the key lectin pathway components ficolin-2 and mannose
binding lectin, are investigated in patients with bronchiectasis.
We demonstrate a significant association between single nucleotide polymorphisms
in the FCN2 gene and disease severity in bronchiectasis. Specifically, patients with
low expressing FCN2 haplotypes have a higher frequency of chronic colonisation,
colonisation with P. aeruginosa, more frequent exacerbations and worse health
related quality of life. An association between MBL deficient genotypes and disease
severity is also demonstrated suggesting an important role for the lectin pathway of
complement in modifying disease severity in bronchiectasis.
In-vitro studies identify that ficolin-2 is the major lectin pathway component
responsible for complement activation on P. aeruginosa and that ficolin-2 binds to a
wide range of clinically relevant pathogens.
Neutrophils isolated from the sputum of patients with bronchiectasis showed
significant alterations in surface receptor expression and function compared to
peripheral blood neutrophils, with a novel effect of neutrophil elastase cleavage of
CD88 contributing to reduced phagocytosis by airway neutrophils. Despite loss of
phagocytic receptors from sputum neutrophils, opsonisation by ficolin-2/MASP-2
complexes still enhanced phagocytosis of P. aeruginosa by sputum neutrophils,
suggesting that ficolin-2 may be relevant in the clearance of P. aeruginosa in the
airway.
In summary, ficolin-2 was found to be an important modifier of disease severity in
bronchiectasis
Knowledge gaps that hamper prevention and control of Mycobacterium avium subspecies paratuberculosis infection
In 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
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