37 million individuals are currently infected with Onchocerca volvulus (O. volvulus), a parasitic nematode that elicits various dermal manifestations and eye damage in man. Disease control is ...primarily based on distributing ivermectin in mass drug administration (MDA) programmes which aim at breaking transmission by eliminating microfilariae (MF), the worm's offspring. The majority of infected individuals present generalized onchocerciasis, which is characterized by hyporesponsive immune responses and high parasite burden including MF. Recently, in areas that have been part of MDA programmes, individuals have been identified that present nodules but are amicrofilaridermic (a-MF) and our previous study showed that this group has a distinct immune profile. Expanding on those findings we determined the immune responses of O. volvulus-infected individuals to a Plasmodium-derived antigen MSP-1 (merozoite surface protein-1), which is required by the parasite to enter erythrocytes.
Isolated PBMCs from O. volvulus-infected individuals (164 MF(+) and 46 a-MF) and non-infected volunteers from the same region (NEN), were stimulated with MSP-1 and the resulting supernatant screened for the presence of IL-5, IL-13, IFN-γ, TNF-α, IL-6, IL-17A and IL-10. These findings were then further analyzed following regression analysis using the covariates MF, ivermectin (IVM) and region. The latter referred to the Central or Ashanti regions of Ghana, which, at the time sampling, had received 8 or 1 round of MDA respectively.
IL-5, IL-13 and IFN-γ responses to MSP-1 were not altered between NEN and O. volvulus-infected individuals nor were any associations revealed in the regression analysis. IL-10, IL-6 and TNF-α MSP-1 responses were, however, significantly elevated in cultures from infected individuals. Interestingly, when compared to a-MF individuals, MSP-induced IL-17A responses were significantly higher in MF(+) patients. Following multivariable regression analysis these IL-10, IL-6, TNF-α and IL-17A responses were all dominantly associated with the regional covariate.
Consequently, areas with a lowered infection pressure due to IVM MDA appear to influence bystander responses to Plasmodium-derived antigens in community members even if they have not regularly participated in the therapy.
Mass drug administration (MDA) programmes against Onchocerca volvulus use ivermectin (IVM) which targets microfilariae (MF), the worm's offspring. Most infected individuals are hyporesponsive and ...present regulated immune responses despite high parasite burden. Recently, with MDA programmes, the existence of amicrofilaridermic (a-MF) individuals has become apparent but little is known about their immune responses. Within this immunoepidemiological study, we compared parasitology, pathology and immune profiles in infection-free volunteers and infected individuals that were MF+ or a-MF. The latter stemmed from villages in either Central or Ashanti regions of Ghana which, at the time of the study, had received up to eight or only one round of MDA respectively. Interestingly, a-MF patients had fewer nodules and decreased IL-10 responses to all tested stimuli. On the other hand, this patient group displayed contrary IL-5 profiles following in vitro stimulation or in plasma and the dampened response in the latter correlated to reduced eosinophils and associated factors but elevated neutrophils. Furthermore, multivariable regression analysis with covariates MF, IVM or the region (Central vs. Ashanti) revealed that immune responses were associated with different covariates: whereas O. volvulus-specific IL-5 responses were primarily associated with MF, IL-10 secretion had a negative correlation with times of individual IVM therapy (IIT). All plasma parameters (eosinophil cationic protein, IL-5, eosinophils and neutrophils) were highly associated with MF. With regards to IL-17 secretion, although no differences were observed between the groups to filarial-specific or bystander stimuli, these responses were highly associated with the region. These data indicate that immune responses are affected by both, IIT and the rounds of IVM MDA within the community. Consequently, it appears that a lowered infection pressure due to IVM MDA may affect the immune profile of community members even if they have not regularly participated in the programmes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Determination of the Cable Factor for Deviated Tendon Bundles Weiher, Hermann; Specht, Eckard; Pfeiffer, Barbara ...
Structural engineering international : journal of the International Association for Bridge and Structural Engineering (IABSE),
02/2008, Letnik:
18, Številka:
1
Journal Article
Recenzirano
This article illustrates how the cable factor of deviated bundle tendons and accordingly the pressure between prestressing steel elements and ducts can be accurately determined. The knowledge of the ...maximum pressure between single tendons and the duct of a tendon bundle is important both to estimate the danger of fatigue fracture of the prestressing steel due to fretting corrosion when using corrugated steel ducts and to estimate the imprints into polyethylene (PE) ducts of unbonded tendons. PE ducts serve as corrosion protection sheathing for tendons. Especially for unbonded tendons, it is necessary to limit the wear of ducts to ensure the corrosion protection of the steel, the durability of the tendon and the tensioned structure. The remaining thickness of PE ducts after loading has to fulfill certain requirements (e.g.according to the guideline for European Technical Approval of Post-Tensioning Kits for Prestressing of Structures, ETAG 013 Ed. June 2002). In the past, graphical methods were applied as well as costly and time-consuming simulations of the arrangement of strands or wires in a duct with the help of small-scale samples. For configurations other than the ones tested or for a greater number of wires in a duct these results cannot be used. That is why two numerical approaches of how to arrange single tendons in a duct were developed. After finding a stable arrangement of the tendons it is possible to determine the cable factors and thus the maximum transverse loading by the help of a twodimensional (2D) truss calculation. Additionally, two simplified approaches for estimating the maximum cable factors are presented. They reduce the calculation effort to different extents. The first approach is based on hydrostatic analogy. The second one is a simplified method that allows for a quick estimation with the help of the relevant parameters. When using PE ducts for bonded post-tensioning fatigue fracture due to fretting occurs at the contacts between single tendons. A simplified model quantifying the maximum inner cable factor is presented for the first time. With the help of the tools presented, the curvature design of deviated tendons and the formulation of restrictions in codes can be reconsidered. In addition to this, they can contribute to a qualified assessment of the durability and efficiency of existing post-tensioning systems or to their development.
Access to real-world database systems and their workloads is an invaluable source of information for database researchers. However, usually such full access is not possible due to tracing overheads, ...data protection, or legal reasons. In this paper, we present a tool set to analyze and compare synthetic and real-world database workloads, their characteristics, and access patterns. This tool set processes SQL workload traces and collects fine-grained access information without requiring direct read access to the production system. To gain insights into large real-world systems, we traced a live production enterprise system of a Global 2000 company and compare it with the synthetic benchmarks TPC-C and TPC-E.
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