Gill's model of the Antarctic Circumpolar Current, revisited: the role of latitudinal variations in wind stress

Adrian Gill’s (1968) model of the Antarctic Circumpolar Current (ACC) is reinterpreted for a stratified, reduced-gravity ocean, where the barotropic streamfunction is replaced by the pycnocline depth, and the bottom drag coefficient by the Gent and McWilliams eddy diffusivity. The resultant model gives a simple description of the lateral structure of the ACC that is consistent with contemporary descriptions of ACC dynamics. The model is used to investigate and interpret the sensitivity of the ACC to the latitudinal profile of the surface wind stress. A substantial ACC remains when the wind jet is shifted north of the model Drake Passage, even by several thousand kilometers. The integral of the wind stress over the circumpolar streamlines is found to be a useful predictor of the magnitude of the volume transport through the model Drake Passage, although it is necessary to correct for basin-wide zonal pressure gradients in order to obtain good quantitative agreement

E. coli O157 on Scottish cattle farms: evidence of local spread and persistence using repeat cross-sectional data

<b>Background</b><p></p> Escherichia coli (E. coli) O157 is a virulent zoonotic strain of enterohaemorrhagic E. coli. In Scotland (1998-2008) the annual reported rate of human infection is 4.4 per 100,000 population which is consistently higher than other regions of the UK and abroad. Cattle are the primary reservoir. Thus understanding infection dynamics in cattle is paramount to reducing human infections.<p></p> A large database was created for farms sampled in two cross-sectional surveys carried out in Scotland (1998 - 2004). A statistical model was generated to identify risk factors for the presence of E. coli O157 on farms. Specific hypotheses were tested regarding the presence of E. coli O157 on local farms and the farms previous status. Pulsed-field gel electrophoresis (PFGE) profiles were further examined to ascertain whether local spread or persistence of strains could be inferred.<p></p> <b>Results</b><p></p> The presence of an E. coli O157 positive local farm (average distance: 5.96km) in the Highlands, North East and South West, farm size and the number of cattle moved onto the farm 8 weeks prior to sampling were significant risk factors for the presence of E. coli O157 on farms. Previous status of a farm was not a significant predictor of current status (p = 0.398). Farms within the same sampling cluster were significantly more likely to be the same PFGE type (p < 0.001), implicating spread of strains between local farms. Isolates with identical PFGE types were observed to persist across the two surveys, including 3 that were identified on the same farm, suggesting an environmental reservoir. PFGE types that were persistent were more likely to have been observed in human clinical infections in Scotland (p < 0.001) from the same time frame.<p></p> <b>Conclusions</b><p></p> The results of this study demonstrate the spread of E. coli O157 between local farms and highlight the potential link between persistent cattle strains and human clinical infections in Scotland. This novel insight into the epidemiology of Scottish E. coli O157 paves the way for future research into the mechanisms of transmission which should help with the design of control measures to reduce E. coli O157 from livestock-related sources

Applying phylogenomics to understand the emergence of Shiga Toxin producing Escherichia coli O157:H7 strains causing severe human disease in the United Kingdom

Shiga Toxin producing Escherichia coli (STEC) O157:H7 is a recently emerged zoonotic pathogen with considerable morbidity. Since the serotype emerged in the 1980s, research has focussed on unravelling the evolutionary events from the E. coli O55:H7 ancestor to the contemporaneous globally dispersed strains. In this study the genomes of over 1000 isolates from human clinical cases and cattle, spanning the history of STEC O157:H7 in the United Kingdom were sequenced. Phylogenetic analysis reveals the ancestry, key acquisition events and global context of the strains. Dated phylogenies estimate the time to the most recent common ancestor of the current circulating global clone to 175 years ago, followed by rapid diversification. We show the acquisition of specific virulence determinates occurred relatively recently and coincides with its recent detection in the human population. Using clinical outcome data from 493 cases of STEC O157:H7 we assess the relative risk of severe disease including HUS from each of the defined clades in the population and show the dramatic effect Shiga toxin complement has on virulence. We describe two strain replacement events that have occurred in the cattle population in the UK over the last 30 years; one resulting in a highly virulent strain that has accounted for the majority of clinical cases in the UK over the last decade. This work highlights the need to understand the selection pressures maintaining Shiga-toxin encoding bacteriophages in the ruminant reservoir and the study affirms the requirement for close surveillance of this pathogen in both ruminant and human populations

Utility of Whole-Genome Sequencing of Escherichia coli O157 for Outbreak Detection and Epidemiological Surveillance

Detailed laboratory characterization of Escherichia coli O157 is essential to inform epidemiological investigations. This study assessed the utility of whole-genome sequencing (WGS) for outbreak detection and epidemiological surveillance of E. coli O157, and the data were used to identify discernible associations between genotypes and clinical outcomes. One hundred five E. coli O157 strains isolated over a 5-year period from human fecal samples in Lothian, Scotland, were sequenced with the Ion Torrent Personal Genome Machine. A total of 8,721 variable sites in the core genome were identified among the 105 isolates; 47% of the single nucleotide polymorphisms (SNPs) were attributable to six “atypical” E. coli O157 strains and included recombinant regions. Phylogenetic analyses showed that WGS correlated well with the epidemiological data. Epidemiological links existed between cases whose isolates differed by three or fewer SNPs. WGS also correlated well with multilocus variable-number tandem repeat analysis (MLVA) typing data, with only three discordant results observed, all among isolates from cases not known to be epidemiologically related. WGS produced a better-supported, higher-resolution phylogeny than MLVA, confirming that the method is more suitable for epidemiological surveillance of E. coli O157. A combination of in silico analyses (VirulenceFinder, ResFinder, and local BLAST searches) were used to determine stx subtypes, multilocus sequence types (15 loci), and the presence of virulence and acquired antimicrobial resistance genes. There was a high level of correlation between the WGS data and our routine typing methods, although some discordant results were observed, mostly related to the limitation of short sequence read assembly. The data were used to identify sublineages and clades of E. coli O157, and when they were correlated with the clinical outcome data, they showed that one clade, Ic3, was significantly associated with severe disease. Together, the results show that WGS data can provide higher resolution of the relationships between E. coli O157 isolates than that provided by MLVA. The method has the potential to streamline the laboratory workflow and provide detailed information for the clinical management of patients and public health interventions

Phylogenetic relationship and virulence composition of Escherichia coli O26:H11 cattle and human strain collections in Scotland; 2002-2020

O26 is the commonest non-O157 Shiga toxin (stx)-producing Escherichia coli serogroup reported in human infections worldwide. Ruminants, particularly cattle, are the primary reservoir source for human infection. In this study, we compared the whole genomes and virulence profiles of O26:H11 strains (n = 99) isolated from Scottish cattle with strains from human infections (n = 96) held by the Scottish Escherichia coli O157/STEC Reference Laboratory, isolated between 2002 and 2020. Bovine strains were from two national cross-sectional cattle surveys conducted between 2002–2004 and 2014–2015. A maximum likelihood phylogeny was constructed from a core-genome alignment with the O26:H11 strain 11368 reference genome. Genomes were screened against a panel of 2,710 virulence genes using the Virulence Finder Database. All stx-positive bovine O26:H11 strains belonged to the ST21 lineage and were grouped into three main clades. Bovine and human source strains were interspersed, and the stx subtype was relatively clade-specific. Highly pathogenic stx2a-only ST21 strains were identified in two herds sampled in the second cattle survey and in human clinical infections from 2010 onwards. The closest pairwise distance was 9 single-nucleotide polymorphisms (SNPs) between Scottish bovine and human strains and 69 SNPs between the two cattle surveys. Bovine O26:H11 was compared to public EnteroBase ST29 complex genomes and found to have the greatest commonality with O26:H11 strains from the rest of the UK, followed by France, Italy, and Belgium. Virulence profiles of stx-positive bovine and human strains were similar but more conserved for the stx2a subtype. O26:H11 stx-negative ST29 (n = 17) and ST396 strains (n = 5) were isolated from 19 cattle herds; all were eae-positive, and 10 of these herds yielded strains positive for ehxA, espK, and Z2098, gene markers suggestive of enterohaemorrhagic potential. There was a significant association (p < 0.001) between nucleotide sequence percent identity and stx status for the bacteriophage insertion site genes yecE for stx2 and yehV for stx1. Acquired antimicrobial resistance genes were identified in silico in 12.1% of bovine and 17.7% of human O26:H11 strains, with sul2, tet, aph(3″), and aph(6″) being most common. This study describes the diversity among Scottish bovine O26:H11 strains and investigates their relationship to human STEC infections

Escherichia coli O157 Infection and Secondary Spread, Scotland, 1999–2008

To determine the proportion of Escherichia coli O157 cases in Scotland attributable to secondary spread, we analyzed data obtained through entire-population enhanced surveillance. We identified 11% of cases as secondary. Secondary cases in single households were younger than secondary cases in outbreaks affecting >1 household and had similar risk for hemolytic uremic syndrome

Temporal and spatial patterns of bovine Escherichia coli O157 prevalence and comparison of temporal changes in the patterns of phage types associated with bovine shedding and human E. coli O157 cases in Scotland between 1998-2000 and 2002-2004

Background: Escherichia coli O157 is an important cause of acute diarrhoea, haemorrhagic colitis and, especially in children, haemolytic uraemic syndrome (HUS). Incidence rates for human E. coli O157 infection in Scotland are higher than most other United Kingdom, European and North American countries. Cattle are considered the main reservoir for E. coli O157. Significant associations between livestock related exposures and human infection have been identified in a number of studies. Results: Animal Studies: There were no statistically significant differences (P = 0.831) in the mean farm-level prevalence between the two studies (SEERAD: 0.218 (95% CI: 0.141-0.32); IPRAVE: 0.205 (95% CI: 0.135-0.296)). However, the mean pat-level prevalence decreased from 0.089 (95% CI: 0.075-0.105) to 0.040 (95% CI: 0.028-0.053) between the SEERAD and IPRAVE studies respectively (P < 0.001). Highly significant (P < 0.001) reductions in mean pat-level prevalence were also observed in the spring, in the North East and Central Scotland, and in the shedding of phage type (PT) 21/28. Human Cases: Contrasting the same time periods, there was a decline in the overall comparative annual reported incidence of human cases as well as in all the major PT groups except 'Other' PTs. For both cattle and humans, the predominant phage type between 1998 and 2004 was PT21/28 comprising over 50% of the positive cattle isolates and reported human cases respectively. The proportion of PT32, however, was represented by few (<5%) of reported human cases despite comprising over 10% of cattle isolates. Across the two studies there were differences in the proportion of PTs 21/28, 32 and 'Other' PTs in both cattle isolates and reported human cases; however, only differences in the cattle isolates were statistically significant (P = 0.002). Conclusion: There was no significant decrease in the mean farm-level prevalence of E. coli O157 between 1998 and 2004 in Scotland, despite significant declines in mean pat-level prevalence. Although there were declines in the number of human cases between the two study periods, there is no statistically significant evidence that the overall rate (per 100,000 population) of human E. coli O157 infections in Scotland over the last 10 years has altered. Comparable patterns in the distribution of PTs 21/28 and 32 between cattle and humans support a hypothesized link between the bovine reservoir and human infections. This emphasizes the need to apply and improve methods to reduce bovine shedding of E. coli O157 in Scotland where rates appear higher in both cattle and human populations, than in other countrie

Genome structural variation in Escherichia coli O157:H7

The human zoonotic pathogen Escherichia coli O157:H7 is defined by its extensive prophage repertoire including those that encode Shiga toxin, the factor responsible for inducing life-threatening pathology in humans. As well as introducing genes that can contribute to the virulence of a strain, prophage can enable the generation of large-chromosomal rearrangements (LCRs) by homologous recombination. This work examines the types and frequencies of LCRs across the major lineages of the O157:H7 serotype. We demonstrate that LCRs are a major source of genomic variation across all lineages of E. coli O157:H7 and by using both optical mapping and Oxford Nanopore long-read sequencing prove that LCRs are generated in laboratory cultures started from a single colony and that these variants can be recovered from colonized cattle. LCRs are biased towards the terminus region of the genome and are bounded by specific prophages that share large regions of sequence homology associated with the recombinational activity. RNA transcriptional profiling and phenotyping of specific structural variants indicated that important virulence phenotypes such as Shiga-toxin production, type-3 secretion and motility can be affected by LCRs. In summary, E. coli O157:H7 has acquired multiple prophage regions over time that act to continually produce structural variants of the genome. These findings raise important questions about the significance of this prophage-mediated genome contingency to enhance adaptability between environments

The real-world problem of care coordination: a longitudinal qualitative study with patients living with advanced progressive illness and their unpaid caregivers.

OBJECTIVES: To develop a model of care coordination for patients living with advanced progressive illness and their unpaid caregivers, and to understand their perspective regarding care coordination. DESIGN: A prospective longitudinal, multi-perspective qualitative study involving a case-study approach. METHODS: Serial in-depth interviews were conducted, transcribed verbatim and then analyzed through open and axial coding in order to construct categories for three cases (sites). This was followed by continued thematic analysis to identify underlying conceptual coherence across all cases in order to produce one coherent care coordination model. PARTICIPANTS: Fifty-six purposively sampled patients and 27 case-linked unpaid caregivers. SETTINGS: Three cases from contrasting primary, secondary and tertiary settings within Britain. RESULTS: Coordination is a deliberate cross-cutting action that involves high-quality, caring and well-informed staff, patients and unpaid caregivers who must work in partnership together across health and social care settings. For coordination to occur, it must be adequately resourced with efficient systems and services that communicate. Patients and unpaid caregivers contribute substantially to the coordination of their care, which is sometimes volunteered at a personal cost to them. Coordination is facilitated through flexible and patient-centered care, characterized by accurate and timely information communicated in a way that considers patients' and caregivers' needs, preferences, circumstances and abilities. CONCLUSIONS: Within the midst of advanced progressive illness, coordination is a shared and complex intervention involving relational, structural and information components. Our study is one of the first to extensively examine patients' and caregivers' views about coordination, thus aiding conceptual fidelity. These findings can be used to help avoid oversimplifying a real-world problem, such as care coordination. Avoiding oversimplification can help with the development, evaluation and implementation of real-world coordination interventions for patients and their unpaid caregivers in the future