Spatial and genomic data to characterize endemic typhoid transmission

BACKGROUND: Diverse environmental exposures and risk factors have been implicated in the transmission of Salmonella Typhi, however, the dominant transmission pathways through the environment to susceptible humans remain unknown. Here, we utilize spatial, bacterial genomic, and hydrological data to refine our view of Typhoid transmission in an endemic setting. METHODS: 546 patients presenting to Queen Elizabeth Central Hospital in Blantyre, Malawi with blood culture-confirmed typhoid fever between April 2015 and January 2017 were recruited to a cohort study. The households of a subset of these patients were geolocated, and 256 S. Typhi isolates were whole genome sequenced. Pairwise single nucleotide variant (SNV) distances were incorporated into a geostatistical modeling framework using multidimensional scaling. RESULTS: Typhoid fever was not evenly distributed across Blantyre, with estimated minimum incidence ranging across the city from less than 15 to over 100 cases/100,000/year. Pairwise SNV distance and physical household distances were significantly correlated (p=0.001). We evaluated the ability of river catchment to explain the spatial patterns of genomics observed, finding that it significantly improved the fit of the model (p=0.003). We also found spatial correlation at a smaller spatial scale, of households living <192 meters apart. CONCLUSIONS: These findings reinforce the emerging view that hydrological systems play a key role in the transmission of typhoid fever. By combining genomic and spatial data, we show how multi-faceted data can be used to identify high incidence areas, understand the connections between them, and inform targeted environmental surveillance, all of which will be critical to shape local and regional typhoid control strategies

Linkage analysis of longitudinal data and design consideration

BACKGROUND: Statistical methods have been proposed recently to analyze longitudinal data in genetic studies. So far, little attention has been paid to examine the relationship among key factors in genetic longitudinal studies including power, the number of families or sibships, and the number of repeated measures per individual subjects. RESULTS: We proposed a variance component model that extends classic variance component models for a single quantitative trait to mapping longitudinal traits. Our model includes covariate effects and allows genetic effects to vary over time. Using our proposed model, we examined the power, pedigree structures, and sample size through simulation experiments. CONCLUSION: Our simulation results provide useful insights into the study design for genetic, longitudinal studies. For example, collecting a small number of large sibships is much more powerful than collecting a large number of small sibships or increasing the number of repeated measures, when the total number of measurements is comparable

Analysis of spatial relationships in three dimensions: tools for the study of nerve cell patterning

<p>Abstract</p> <p>Background</p> <p>Multiple technologies have been brought to bear on understanding the three-dimensional morphology of individual neurons and glia within the brain, but little progress has been made on understanding the rules controlling cellular patterning. We describe new matlab-based software tools, now available to the scientific community, permitting the calculation of spatial statistics associated with 3D point patterns. The analyses are largely derived from the Delaunay tessellation of the field, including the nearest neighbor and Voronoi domain analyses, and from the spatial autocorrelogram.</p> <p>Results</p> <p>Our tools enable the analysis of the spatial relationship between neurons within the central nervous system in 3D, and permit the modeling of these fields based on lattice-like simulations, and on simulations of minimal-distance spacing rules. Here we demonstrate the utility of our analysis methods to discriminate between two different simulated neuronal populations.</p> <p>Conclusion</p> <p>Together, these tools can be used to reveal the presence of nerve cell patterning and to model its foundation, in turn informing on the potential developmental mechanisms that govern its establishment. Furthermore, in conjunction with analyses of dendritic morphology, they can be used to determine the degree of dendritic coverage within a volume of tissue exhibited by mature nerve cells.</p

Crop Updates 2006 - Oilseeds

This session covers thirteen papers from different authors: 1. INTRODUCTION, Graham Walton, CONVENOR, Department of Agriculture 2. The performance of new TT canola varieties in National Variety Testing (NVT) WA, Fiona Martin, Research Agronomist, Agritech Crop Research 3. Comparison of TT Canola Varieties in Oilseeds WA Trials – 2005, Collated by G.H. Walton, Department of Agriculture, WA, from a collaboration between Oilseeds WA, Seed Companies, Agronomists and Growers 4. An overview of the potential for a Biofuels Industry in Western Australia, Anne Wilkins and Nathan Hancock, Department of Agriculture 5. Retrieval of fertile progeny from interspecific crosses between Brassica napus and B. carinata using microspore culture, Matthew Nelson, Marie-Claire Castello, Linda Thomson, Anouska Cousin, Guijun Yan and Wallace Cowling; School of Plant Biology (M084), The University of Western Australia 6. Advances in canola blackleg epidemiology and its implication in understanding and managing the disease, Moin Salam, Bill MacLeod, Ravjit Khangura, Jean Galloway and Art Diggle, Department of Agriculture 7. Effect of fertiliser phosphorus and nitrogen on grain yields and concentration of oil and protein of canola grain, R.F. Brennan, M.D.A. Bolland, Department of Agriculture 8. Effect of applying fertiliser potassium and nitrogen on canola grain yields and concentration of oil and protein in grain, R.F. Brennan, M.D.A. Bolland, Department of Agriculture 9. Effect of fertiliser nitrogen and sulfer on canola yields and concentration of oil in grain, R.F. Brennan, M.D.A. Bolland, Department of Agriculture 10. Uptake of K from topsoil and subsoil by canola, P.M. Damon and Z. Rengel, Faculty of Natural and Agricultural Sciences, The University of WA 11. Accumulation of P and K by canola plants, Terry Rose, Zed Rengel and Qifu Ma, Faculty of Natural and Agricultural Sciences, The University of WA 12. Varied response from applying nitrogen at late flowering in canola! Dave Eksteen, Agronomist, United Farmers Cooperative 13. To investigate the timing, rate and placement of nitrogen on canola – Jerdacuttup 2005, Dave Eksteen, Agronomist, United Farmers Cooperativ

Rapid Detection and Subtyping of Human Influenza A Viruses and Reassortants by Pyrosequencing

Background: Given the continuing co-circulation of the 2009 H1N1 pandemic influenza A viruses with seasonal H3N2 viruses, rapid and reliable detection of newly emerging influenza reassortant viruses is important to enhance our influenza surveillance. Methodology/Principal Findings: A novel pyrosequencing assay was developed for the rapid identification and subtyping of potential human influenza A virus reassortants based on all eight gene segments of the virus. Except for HA and NA genes, one universal set of primers was used to amplify and subtype each of the six internal genes. With this method, all eight gene segments of 57 laboratory isolates and 17 original specimens of seasonal H1N1, H3N2 and 2009 H1N1 pandemic viruses were correctly matched with their corresponding subtypes. In addition, this method was shown to be capable of detecting reassortant viruses by correctly identifying the source of all 8 gene segments from three vaccine production reassortant viruses and three H1N2 viruses. Conclusions/Significance: In summary, this pyrosequencing assay is a sensitive and specific procedure for screening large numbers of viruses for reassortment events amongst the commonly circulating human influenza A viruses, which is mor

Long-Term Follow-Up of a High School Alcohol Misuse Prevention Program's Effect on Students' Subsequent Driving

Alcohol-related injuries, particularly motor vehicle, are an important cause of adolescent mortality. School-based alcohol prevention programs have not been evaluated in terms of driving outcomes. This study examined the effects on subsequent driving of a high school-based alcohol prevention program. Methods : The Alcohol Misuse Prevention Study included a randomized test of the effectiveness of an alcohol misuse prevention curriculum conducted among 4635 10th-grade students. Students were assigned to intervention ( n = 1820) or control ( n = 2815) groups and were followed for an average of 7.6 years after licensure, which typically occurred during or shortly after 10th grade. Outcomes examined included alcohol-related and other serious offenses, and at-fault, single-vehicle, and alcohol-related crashes. Results : Only serious offenses (which included alcohol-related) had a significant treatment effect (statistically marginal) after we adjusted for sex, age, race, alcohol use/misuse, family structure, presence of prelicense offenses, age of driver licensure, and parental attitudes toward teen drinking. The effect was found only during the first year of licensure (estimated adjusted relative risk = 0.80, confidence interval = 0.63–1.01). Two first-year serious offense interactions were found. The positive effect was strongest among the largest subgroup of students, those who were drinking less than one drink per week on average before the curriculum, compared with those who drank more than one drink per week ( p = 0.009). The effect was also stronger for the small subgroup of students whose parents had not expressed disapproval of teens’ drinking, compared with those whose parents had disapproved ( p = 0.004). Conclusions : These findings suggest that a high school-based alcohol prevention program can positively affect subsequent driving, particularly that of students who do not use alcohol regularly. The results highlight the need to start prevention efforts early and extend them beyond the initial exposure to driving. Programs should incorporate the differing backgrounds of the students.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65493/1/j.1530-0277.2001.tb02227.x.pd

Influence of Two Vaccination Campaigns on Genetic Diversity of Invasive Neisseria meningitidis Isolates in Northern Spain (1997–2008)

BACKGROUND: Neisseria meningitidis diversifies rapidly, due to its high recombination rates. The aim of this study was to analyze the possible impact of two vaccination campaigns (a once-off A/C polysaccharide vaccination campaign in people aged 18 months to 20 years old in 1997, and a meningococcal C conjugate vaccination campaign in children aged < or = 6 years old from 2000 to 2008) on diversification of the population of invasive isolates obtained between 1997 and 2008. All of the 461 available isolates were included (2, 319, 123, 11 and 6 belonging to serogroups A, B, C, Y and W-135, respectively). METHODOLOGY/PRINCIPAL FINDINGS: The isolates were analyzed for diversity using multilocus sequence typing, eBURST and the S.T.A.R.T.2 program. One hundred and seven sequence types (ST) and 20 clonal complexes were obtained. Five different STs (ST11, ST8, ST33, ST1163 and ST3496) included 56.4% of the isolates. With the exception of ST11, all other STs were associated with a specific serogroup. Epidemic circulation of serogroup C ST8 isolates was detected in 1997-1998, as well as epidemic circulation of ST11 isolates (serogroups B and C) in 2002-2004. The epidemic behavior of serogroup B ST11 (ST11_B:2a:P1.5) was similar, although with lesser intensity, to that of ST11 of serogroup C. Although clonality increased during epidemic years, the overall diversity of the meningococcal population did not increase throughout the 12 years of the study. CONCLUSION: The overall diversity of the meningococcal population, measured by the frequency of STs and clonal complexes, numbers of alleles, polymorphic sites, and index of association, remained relatively constant throughout the study period, contradicting previous findings by other researchers

The Pseudomonas aeruginosa PSL Polysaccharide Is a Social but Noncheatable Trait in Biofilms

Extracellular polysaccharides are compounds secreted by microorganisms into the surrounding environment, and they are important for surface attachment and maintaining structural integrity within biofilms. The social nature of many extracellular polysaccharides remains unclear, and it has been suggested that they could function as either cooperative public goods or as traits that provide a competitive advantage. Here, we empirically tested the cooperative nature of the PSL polysaccharide, which is crucial for the formation of biofilms in Pseudomonas aeruginosa. We show that (i) PSL is not metabolically costly to produce; (ii) PSL provides population-level benefits in biofilms, for both growth and antibiotic tolerance; (iii) the benefits of PSL production are social and are shared with other cells; (iv) the benefits of PSL production appear to be preferentially directed toward cells which produce PSL; (v) cells which do not produce PSL are unable to successfully exploit cells which produce PSL. Taken together, this suggests that PSL is a social but relatively nonexploitable trait and that growth within biofilms selects for PSL-producing strains, even when multiple strains are on a patch (low relatedness at the patch level). IMPORTANCE: Many studies have shown that bacterial traits, such as siderophores and quorum sensing, are social in nature. This has led to an impression that secreted traits act as public goods, which are costly to produce but benefit both the producing cell and its surrounding neighbors. Theories and subsequent experiments have shown that such traits are exploitable by asocial cheats, but we show here that this does not always hold true. We demonstrate that the Pseudomonas aeruginosa exopolysaccharide PSL provides social benefits to populations but that it is nonexploitable, because most of the fitness benefits accrue to PSL-producing cells. Our work builds on an increasing body of work showing that secreted traits can have both private and public benefits to cells

Pseudomonas aeruginosa Overrides the Virulence Inducing Effect of Opioids When It Senses an Abundance of Phosphate

The gut during critical illness represents a complex ecology dominated by the presence of healthcare associated pathogens, nutrient scarce conditions, and compensatory host stress signals. We have previously identified key environmental cues, opioids and phosphate depletion that independently activate the virulence of Pseudomonas aeruginosa. Opioids induce quinolone signal production (PQS), whereas phosphate depletion leads to a triangulated response between MvfR-PQS, pyoverdin, and phosphosensory/phosphoregulatory systems (PstS-PhoB). Yet how P. aeruginosa manages its response to opioids during nutrient scarce conditions when growth is limited and a quorum is unlikely to be achieved is important in the context of pathogenesis in gut during stress. To mimic this environment, we created nutrient poor conditions and exposed P. aeruginosa PAO1 to the specific k-opioid receptor agonist U-50,488. Bacterial cells exposed to the k-opioid expressed a striking increase in virulence- and multi-drug resistance-related genes that correlated to a lethal phenotype in C. elegans killing assays. Under these conditions, HHQ, a precursor of PQS, rather than PQS itself, became the main inducer for pqsABCDE operon expression. P. aeruginosa virulence expression in response to k-opioids required PqsE since ΔPqsE was attenuated in its ability to activate virulence- and efflux pumps-related genes. Extracellular inorganic phosphate completely changed the transcriptional response of PAO1 to the k- opioid preventing pqsABCDE expression, the activation of multiple virulence- and efflux pumps-related genes, and the ability of P. aeruginosa to kill C. elegans. These results indicate that when P. aeruginosa senses resource abundance in the form of phosphate, it overrides its response to compensatory host signals such as opioids to express a virulent and lethal phenotype. These studies confirm a central role for phosphate in P. aeruginosa virulence that might be exploited to design novel anti- virulence strategies