Geogenomic segregation and temporal trends of human pathogenic Escherichia coli o157:H7, Washington, USA, 2005-2014

The often-noted and persistent increased incidence of Escherichia coli O157:H7 infections in rural areas is not well understood. We used a cohort of E. coli O157:H7 cases reported in Washington, USA, during 2005–2014, along with phylogenomic characterization of the infecting isolates, to identify geographic segregation of and temporal trends in specific phylogenetic lineages of E. coli O157:H7. Kernel estimation and generalized additive models demonstrated that pathogen lineages were spatially segregated during the period of analysis and identified a focus of segregation spanning multiple, predominantly rural, counties for each of the main clinical lineages, Ib, IIa, and IIb. These results suggest the existence of local reservoirs from which humans are infected. We also noted a secular increase in the proportion of lineage IIa and IIb isolates. Spatial segregation by phylogenetic lineage offers the potential to identify local reservoirs and intervene to prevent continued transmission

Chapter Five. Systematic review results by biomarker classifications

5.1 Markers of Absorption and Permeability Overview 5.2 Markers of Absorption 5.3 Markers of Permeability 5.4 Markers of Digestion 5.5 Markers of Intestinal Inflammation and Intestinal Immune Activation 5.6 Markers of Systemic Inflammation and Systemic Immune Activation 5.7 Markers of Microbial Drivers 5.8 Markers of Nonspecific Intestinal Injury 5.9 Markers of Extra-Small Intestinal Function 5.10 Relationships Between Markers of EED, Including Histopathology 5.11 Relationships between EED Biomarkers and Growth or Other Outcomes of Interesthttps://digitalcommons.wustl.edu/tropicalenteropathybook/1006/thumbnail.jp

Chapter Three. EED library as a basis for systematic reviews

3.1 Defining Systematic Review Question Priorities 3.2 Determining Relevance to the Systematic Review 3.3 Acquisition of References and Copyright Fair Use Compliance 3.4 Documenting Relevance to the Systematic Review 3.5 Data Extraction for the Systematic Review 3.6 EED Library: Search Results Overview 3.7 Quality Control 3.8 EED Library Statushttps://digitalcommons.wustl.edu/tropicalenteropathybook/1004/thumbnail.jp

J Regularization Improves Imbalanced Multiclass Segmentation

We propose a new loss formulation to further advance the multiclass segmentation of cluttered cells under weakly supervised conditions. When adding a Youden's J statistic regularization term to the cross entropy loss we improve the separation of touching and immediate cells, obtaining sharp segmentation boundaries with high adequacy. This regularization intrinsically supports class imbalance thus eliminating the necessity of explicitly using weights to balance training. Simulations demonstrate this capability and show how the regularization leads to correct results by helping advancing the optimization when cross entropy stagnates. We build upon our previous work on multiclass segmentation by adding yet another training class representing gaps between adjacent cells. This addition helps the classifier identify narrow gaps as background and no longer as touching regions. We present results of our methods for 2D and 3D images, from bright field images to confocal stacks containing different types of cells, and we show that they accurately segment individual cells after training with a limited number of images, some of which are poorly annotated

Chapter Six. Conclusions and future implications

6.1 Summary of Findings 6.2 Future Biomarker and Diagnostics Researchhttps://digitalcommons.wustl.edu/tropicalenteropathybook/1007/thumbnail.jp

Chapter One. Environmental enteric dysfunction (EED) background

1.1 EED History and Overview 1.2 An Old Problem Requiring New Knowledge 1.3 Pathophysiologic Processes and Consequences of EED 1.4 The Role of Biomarkers and Diagnostics in EED 1.5 Scientific Basis for this Reviewhttps://digitalcommons.wustl.edu/tropicalenteropathybook/1002/thumbnail.jp

Front Matter

The front matter contains the title page, table of contents, list of tables, list of figures, list of appendices, acknowledgements, abbreviations and synopsis.https://digitalcommons.wustl.edu/tropicalenteropathybook/1001/thumbnail.jp

Appendices

https://digitalcommons.wustl.edu/tropicalenteropathybook/1008/thumbnail.jp

Evolutionary patchwork of an insecticidal toxin shared between plant-associated pseudomonads and the insect pathogens Photorhabdus and Xenorhabdus.

BACKGROUND: Root-colonizing fluorescent pseudomonads are known for their excellent abilities to protect plants against soil-borne fungal pathogens. Some of these bacteria produce an insecticidal toxin (Fit) suggesting that they may exploit insect hosts as a secondary niche. However, the ecological relevance of insect toxicity and the mechanisms driving the evolution of toxin production remain puzzling. RESULTS: Screening a large collection of plant-associated pseudomonads for insecticidal activity and presence of the Fit toxin revealed that Fit is highly indicative of insecticidal activity and predicts that Pseudomonas protegens and P. chlororaphis are exclusive Fit producers. A comparative evolutionary analysis of Fit toxin-producing Pseudomonas including the insect-pathogenic bacteria Photorhabdus and Xenorhadus, which produce the Fit related Mcf toxin, showed that fit genes are part of a dynamic genomic region with substantial presence/absence polymorphism and local variation in GC base composition. The patchy distribution and phylogenetic incongruence of fit genes indicate that the Fit cluster evolved via horizontal transfer, followed by functional integration of vertically transmitted genes, generating a unique Pseudomonas-specific insect toxin cluster. CONCLUSIONS: Our findings suggest that multiple independent evolutionary events led to formation of at least three versions of the Mcf/Fit toxin highlighting the dynamic nature of insect toxin evolution