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© 2018 Waite, Vanwonterghem, Rinke, Parks, Zhang, Takai, Sievert, Simon, Campbell, Hanson, Woyke, Klotz and Hugenholtz. In our original publication, we proposed the phylum name Epsilonbacteraeota according to a proposal to modify Rule 8 of the International Code of Nomenclature of Prokaryotes, under which the suffix -aeota would be used to denote prokaryotic phyla (Oren et al., 2015). An addendum to this proposal was recently made whereby the shorter suffix -ota, instead of -aeota, be added to the stem of the name of one of the contained classes (Whitman et al., 2018). In accordance with this amendment, and the requirement that a class name is derived from a type genus (Oren et al., 2015), we propose to replace the name Epsilonbacteraeota with Campylobacterota. This change does not affect subordinate ranks of the phylum. Campylobacterota (Cam.py.lo.bac.ter.o'ta. N.L. neut. n. Campylobacter type genus of the type order of the type class of the phylum; suff. -ota, proposed ending to denote a phylum; N.L. neut. pl. n. Campylobacterota the phylum of the class Campylobacteria).

Due to our ageing population, emergency departments (ED) in acute care facilities are dealing with increased transfers of residents from Residential Aged Care Facilities (RACF). These patients are at risk of acts of provision of unwanted treatments, omission of care, and adverse outcomes including increased mortality directly associated with gaps in transfer information. For at least 30 years, research has attempted to address this frequency of information gaps, which in general are thought to be stemming from RACFs. Research to date has largely focused on identifying and quantifying gaps to highlight the magnitude of the problem, and on developing localised transitional minimum datasets. Further attempts have been made to define the appropriateness of transfer and the subsequent impacts of transfer on ED length of stay. As a result, numerous paper and electronic information transfer tools have been introduced. New transfer forms and formats have led to some success in improving the amount of documentation transferred with residents to ED. However, this has not been sustained over time, and there has been little agreement toward developing a uniform mandated transitional minimum dataset. Despite the focus on transfer documents and information gaps there is a dearth of research looking at clinician authorship or clinician documentation practices during transfer, and few studies include ambulance services and their role in information transfer. The aim of this study is to identify practice contributing to the stubbornness of information gaps in the transfer of aged residents from RACF to ED via ambulance. This study examined documents and clinician documentation practices as implemented across transfer from RACF via ambulance to emergency. A pragmatic approach guided the research design. Retrospective document review was used to examine the connection between documents, document content, the sites of practice and the practices of clinicians undertaking transfer of RACF residents. This approach acknowledged documents as collectively social products that represent organisations and users, and therefore also organisational work and work-practice complexities. Electronically scanned documents used across transfer by RACFs, the ambulance service and emergency triage were accessed via the study hospital’s digital medical record system. The digital medical record provided easy access to information from all three groups of interest. Collection of transfer documents and transfer narratives from the same sources and transfer episodes facilitated examination of the relationship of documents to documentation and vice versa, as well as of the trackability of episodic transfer information across organisations. Samples were drawn from 89 transfers undertaken between 1 December 2013 and 31 January 2014. Eighty of these cases met the selection criteria. Data samples collected were: all transfer document types sent from RACFs, all electronic ambulance case records, and all ED triage documents, resulting in 240 cross-facility transfer episodes. From these, 199 verbatim free-text narratives authored by clinicians facilitating each transfer were collected. In addition, 48 yellow transfer envelopes used for transfer by RACFs (not available in the digital medical record) were also collected. A mixed method convergent parallel study design was employed in which quantitative and qualitative data are collected in parallel, analysed separately and then brought together in discussion. Practice Theory was selected as the primary lens for qualitative analysis, applying the concepts of doings, sayings and teleoaffectivity with the concepts of zooming in and zooming out to the overall interconnected web of transfer. Transfer narratives were quantitatively examined for standardisation of salient information using a common handover mnemonic, SBAR (Situation, Background, Assessment, Recommendation or Request). Results identified the foci of information and the presence or absence of salient information in transfer narratives, enabling theorisation of how information is cued by the design of tools and situational context in each of the three groups of interest. The findings showed that consistency, availability and predictability of information were negatively affected by a lack of standardisation of RACF transfer information, despite ambulance and ED triage documents being reasonably standardised. The different contextual perspectives of the three organisations gave rise to different information foci: RACF staff focused on access to resources; ambulance staff focused on identifying a primary physiological concern; and ED triage staff focused on aligning physiological issues with numerical scales of urgency. This thesis makes a novel contribution to understanding why information gaps from RACF to ED persist. All of the transfer tools in use were found to be predominately designed as records of care/event, rather than as information sharing tools that accommodate complex information. The results also show that socio-contextual practices narrowly focus narratives on the activities of the author, or on the context of the situation, to the exclusion of other relevant information. Information intended to avert risk is reliant on experiential prediction and subsequent experiential interpretation of the narrative. Transfers fitting the popular expectations of acute ED services are carried out with surprisingly little transfer information, often relying on implicit mutuality. However, resourcerelated transfers that have limited mutual consensus or underlying agreement pre-condition extensive justifications from RACFs to legitimise transfer, because the usual accepted services of the ED are pre-emptively broadened or strained. The detail of the narrative has little bearing on the type, completeness or availability of additional documents sent by RACF in transfer. Because each of these practices (mutuality and extensive narration and argument) work (i.e. the goal of transfer is successfully enacted) there is little incentive for RACFs to standardise practice. Ambulance case narratives implied on-site verbal exchanges between RACFs and paramedics, and generated content capable of filling some information gaps. This finding substantiated the value of the ambulance document and narrative and suggests that it may be a starting point on which to base an interdisciplinary information bridging tool. This study concludes that current transfer tools used by RACF, ambulance services and ED triage generate site-oriented information with little incentive for collaboration or social exchange. The results of this study have the potential to reduce information gaps common across transfer at the clinical, policy and system design levels. More importantly, these findings have the potential to improve continuity and safety for RACF residents transferred to ED.

The human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) appear to have originated by cross-species transmission of simian immunodeficiency virus (SN) from asymptomatically infected African primates. Few of the SIVs characterized to date efficiently infect human primary lymphocytes. Interesting, two of the three identified to infect such cultures (SIVsm and SIVcpz) have appeared in human populations as genetically related HIVs. In the present study, we characterized a novel SIV isolate from an East African monkey of the Cercopithecus genus, the l'hoest monkey (C. l'hoesti), which we designated SIVlhoest. This SN isolate efficiently infected both human and macaque lymphocytes and resulted in a persistent infection of macaques, characterized by high primary virus load and a progressive decline in circulating CD4 lymphocytes, consistent with progression to AIDS. Phylogenetic analyses showed that SIVIhoest is genetically distinct from other previously characterized primate lentiviruses but clusters in the same major lineage as SIV from mandrills (SIVmnd), a West African primate species. Given the geographic distance between the ranges of l'hoest monkeys and mandrills, this may indicate that SIVmnd arose through cross-species transmission from close relatives of l'hoest monkeys that are sympatric with mandrills. These observations lend support to the hypothesis that the primate lentiviruses originated and coevolved within monkeys of the Cercopithecus genus. Regarded in this light, lentivirus infections of primates not belonging to the Cercopithecus genus may have resulted from cross-species transmission in the not-too-distant past.

Mucosa-associated adherent, invasive Escherichia coli (AIEC), found in increased number in Crohn���s disease (CD) ileal and colonic mucosae, can survive and replicate within underlying host immune competent cells (e.g. macrophages and dendritic cells) without triggering host cell death. The intra-macrophage environment plays an essential role in bacterial killing where engulfed bacteria are exposed to a hostile environment of low pH, high levels of proteolytic/lysosomal enzymes, high nitrosative and high oxidative stress, and the activation of a respiratory burst with generation of superoxide ions. Although a few stress response genes have been identified that likely support the paradigm ileal AIEC isolate LF82 to survive and replicate within the macrophage, the key molecular mechanisms involved in supporting Crohn���s disease (CD) mucosa-associated AIEC to resist killing by host mucosal macrophages within harsh environment of the phagolysosome still remains largely unclear. Here we aimed to compare the ability of a number of E. coli strains to survive and replicate inside macrophages, including a number of clinical isolates (from CD, colorectal cancer (CRC) and ulcerative colitis (UC) patients and other infective or non-inflamed sources), and this to toleration of growth in chemical-induced stress conditions mimicking the intra-phagolysosome environment. In addition, a focus was to further understand the molecular mechanisms responsible for acid tolerance of the paradigm CD isolates and examine their replication within macrophages defective in NF-��B pathway signalling. Finally, to also assess whether CD AIEC possess ability to alter host oxidative stress response gene expression in macrophages to support their survival/replication. Both ileal and colonic CD isolates (AIEC) were found to possess ability to either survive and/or replicate within murine macrophages (i.e. J774-A1 cell-line and wild-type (WT) C57BL/6 bone marrow derived macrophages [BMDM]) and to tolerate all stress conditions mimicking those within the phagolysosome, e.g. low nutrient, high acid, high nitrosative, high oxidative stress including exposure to superoxide ions. Interestingly pathogenic E. coli isolates from urinary tract infection (UTI) and some healthy-mucosa associated E. coli strains behaved similarly. Crohn���s AIEC were unable to survive and replicate inside Nf��b1-/- and Nf��b2-/- BMDM, whilst they survived/replicated within WT and c-Rel-/- BMDM. Thus Crohn���s AIEC survival and replication appears dependent on host NF��B signalling within the macrophage. Conversely, all CRC and UC isolates tested and the majority of laboratory E. coli strains studied were unable to survive inside murine J774-A1 macrophage phagolysosomes and they were also intolerant to most stress conditions, in particular superoxidative stress. Colonic CD AIEC isolate HM605 showed higher initial levels of expression of acid response genes gadA and gadB that may support adaptation to the intra-macrophage phagolysosome niche. Adaptation to an intra-macrophage lifestyle appeared not to be through any ability to alter host macrophage oxidative stress response to infection as no differential changes were observed in the expression of 84 host genes related to oxidative stress to that seen with non-replicating laboratory E. coli strain. Overall this study provides new insight into how CD mucosa-associated E. coli isolates resist killing by mucosal macrophages through adaptation to the acidic, high oxidative environment within the macrophage phagolysosome. The data may support future development of new therapeutic strategies that target the fundamental pathology of CD, in particular support a reduction in bacterial persistence/increased killing of intra-macrophage E. coli in CD patient mucosae.

It has long been proposed that a high intake of dietary fibre promotes good intestinal health. Work performed previously by our research group suggests that soluble dietary fibre might have a particularly beneficial impact on intestinal health via its ability to inhibit potentially harmful interactions between bacterial pathogens and the gut epithelium. The aims of this thesis were to evaluate soluble plantain NSP for its ability to disrupt the epithelial interactions of diarrhoeal pathogens C. difficile and Enterotoxigenic Escherichia coli (ETEC), as well as other bacterial components implicated in diarrhoeal disease. Work was also performed to characterise the specific inhibitory fraction of plantain NSP, and in addition, to establish the molecular mechanism underlying its inhibitory activity. A range of soluble dietary fibres were shown to significantly inhibit the in vitro epithelial adhesion of C. difficile and ETEC, but out of all the fibres tested, soluble plantain NSP exhibited the highest efficacy. Plantain NSP also significantly inhibited the epithelial adhesion of eleven C. difficile clinical isolates, irrespective of their toxin expression or ribotype status. Furthermore, plantain NSP blocked the epithelial interactions of five purified C. difficile spore preparations. In addition to its anti-adhesive effects, soluble plantain NSP significantly down-regulated the pro-inflammatory, cytotoxicity and apoptotic response induced by C. difficile and its toxins. Similar effects were also found with respect to mucosally-associated E. coli isolated from ulcerative colitis (UC) patients, as well as bacterial components such as flagellin and LPS. Results demonstrated that the inhibitory activity of plantain NSP was mediated by its acidic polysaccharide fraction, which is mainly composed of pectic material. In addition, it was shown that soluble plantain disrupted bacterial-epithelial interactions via an interaction with the intestinal epithelium. Whilst plantain NSP induced increased cellular chloride secretion, this mechanism was not responsible for inhibitory activity. It was also hypothesised that plantain NSP might mimic intestinal MUC2 glycans by interacting with cell-surface galectin-3, with consequent nuclear localisation of β-catenin and down-regulation of inflammatory cytokines. Whilst plantain NSP was shown to induce activation of β-catenin, the knockdown of surface galectin-3 expression had no effect on inhibitory activity. Thus, the specific mechanism underlying the inhibitory activity of plantain NSP requires further investigation. This work supports the hypothesis that soluble plantain fibre can inhibit harmful interactions between bacteria and the human intestinal epithelium. Indeed, these studies provide convincing evidence to suggest that soluble plantain fibre, acting as a ‘contrabiotic’, could be developed as a potential prophylaxis or treatment against C. difficile and ETEC, which represent the main cause of antibiotic-associated diarrhoea and traveller’s diarrhoea, respectively. In addition, dietary supplementation with soluble plantain NSP may also confer a therapeutic benefit in inflammatory bowel disease (IBD).