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Coeliac disease (CD) and Type 1 diabetes mellitus (T1DM) are immune-mediated diseases. Emerging evidence suggests that dysbiosis in the gut microbiome plays a role in the pathogenesis of both diseases and may also be associated with the development of neuropathy. The primary goal in this cross-sectional pilot study was to identify whether there are distinct gut microbiota alterations in children with CD (n = 19), T1DM (n = 18) and both CD and T1DM (n = 9) compared to healthy controls (n = 12). Our second goal was to explore the relationship between neuropathy (corneal nerve fiber damage) and the gut microbiome composition. Microbiota composition was determined by 16S rRNA gene sequencing. Corneal confocal microscopy was used to determine nerve fiber damage. There was a significant difference in the overall microbial diversity between the four groups with healthy controls having a greater microbial diversity as compared to the patients. The abundance of pathogenic proteobacteria Shigella and E. coli were significantly higher in CD patients. Differential abundance analysis showed that several bacterial amplicon sequence variants (ASVs) distinguished CD from T1DM. The tissue transglutaminase antibody correlated significantly with a decrease in gut microbial diversity. Furthermore, the Bacteroidetes phylum, specifically the genus Parabacteroides was significantly correlated with corneal nerve fiber loss in the subjects with neuropathic damage belonging to the diseased groups. We conclude that disease-specific gut microbial features traceable down to the ASV level distinguish children with CD from T1DM and specific gut microbial signatures may be associated with small fiber neuropathy. Further research on the mechanisms linking altered microbial diversity with neuropathy are warranted.  相似文献   
2.
An important and difficult part of project management is the conceptualization stage – particularly when dealing with multiple powerful stakeholders and ‘messy’ situations. Pragmatism provides a way forward that makes central the ‘concepts’ being used to conceptualize the project (e.g. ‘timeliness’ or ‘sustainability’). This paper argues for a sequence of two approaches suggested in the literature that combine this pragmatism and soft systems thinking to conceptualize projects. These are Alexander’s ‘Synthesis’ [1] and Checkland’s ‘CATWOE’ [2]. The first identifies concepts or worldviews, the second uses these to draft a series of ‘what needs to be done’ statements. In the way of Pragmatic Systems Inquiry, these approaches suggested from the literature are then compared to a real case study: the LC-25 project.  相似文献   
3.
The conceptualisation of complex projects requires an ability to manage the contradictory claims of stakeholders. Argument mapping provides one means of helping with this problem, offering a scientific mutable mobile or collaborative cartography. It structures what is known from the warrants and rebuttals inherent in what is said. It also offers opportunity to give voice to all stakeholders, thus aligning with and giving acknowledgement to the Australian cultural norm of a ‘fair go’. In this paper we explain why and how argument mapping using Toulmin's model can be used to help project managers conceptualise complex projects. This includes explaining the long association between dialectic argument and knowledge claims, presenting a common pedigree between argument and the philosophy of science. Following that, we explain the means and motive behind putting dialectic arguments into a graphical form. Next, the paper provides an illustration of an argument map drafted to highlight the concepts involved in managing an Australian mining export project. Australian mining projects dependent on the China market need to be aware of the growing geo-political tensions between the US and China. The mapping is used to emerge some planning concepts, providing a means of sense-making or structuring, a complex Australian project.  相似文献   
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