Hidden Markov modeling of eye movements with image information leads to better discovery of regions of interest

Conference Theme: Integrating Psychological, Philosophical, Linguistic, Computational and Neural PerspectivesPoster Session 2: no. 56Hidden Markov models (HMM) can describe the spatial and temporal characteristics of eye-tracking recordings in cognitive tasks. Here, we introduce a new HMM approach. We developed HMMs based on fixation locations and we also used image information as an input feature. We demonstrate the benefits of the newly proposed model in a face recognition study wherein an HMM was developed for every subject. Discovery of regions of interest on facial stimuli is improved compared to earlier approaches. Moreover, clustering of the newly developed HMMs lead to very distinct groups. The newly developed approach also allows reconstructing image information at fixation.postprin

Population genetic structure of Streptococcus pneumoniae in Kilifi, Kenya, prior to the introduction of pneumococcal conjugate vaccine.

BACKGROUND: The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in Kenya in 2011. Introduction of any PCV will perturb the existing pneumococcal population structure, thus the aim was to genotype pneumococci collected in Kilifi before PCV10. METHODS AND FINDINGS: Using multilocus sequence typing (MLST), we genotyped >1100 invasive and carriage pneumococci from children, the largest collection genotyped from a single resource-poor country and reported to date. Serotype 1 was the most common serotype causing invasive disease and was rarely detected in carriage; all serotype 1 isolates were members of clonal complex (CC) 217. There were temporal fluctuations in the major circulating sequence types (STs); and although 1-3 major serotype 1, 14 or 23F STs co-circulated annually, the two major serotype 5 STs mainly circulated independently. Major STs/CCs also included isolates of serotypes 3, 12F, 18C and 19A and each shared ≤ 2 MLST alleles with STs that circulate widely elsewhere. Major CCs associated with non-PCV10 serotypes were predominantly represented by carriage isolates, although serotype 19A and 12F CCs were largely invasive and a serotype 10A CC was equally represented by invasive and carriage isolates. CONCLUSIONS: Understanding the pre-PCV10 population genetic structure in Kilifi will allow for the detection of changes in prevalence of the circulating genotypes and evidence for capsular switching post-vaccine implementation

Multiple Colonization with S. pneumoniae before and after Introduction of the Seven-Valent Conjugated Pneumococcal Polysaccharide Vaccine

Simultaneous carriage of more than one strain of Streptococcus pneumoniae promotes horizontal gene transfer events and may lead to capsule switch and acquisition of antibiotic resistance. We studied the epidemiology of cocolonization with S. pneumoniae before and after introduction of the seven-valent conjugated pneumococcal vaccine (PCV7)

Serotype Distribution and Invasive Potential of Group B Streptococcus Isolates Causing Disease in Infants and Colonizing Maternal-Newborn Dyads

Serotype-specific polysaccharide based group B streptococcus (GBS) vaccines are being developed. An understanding of the serotype epidemiology associated with maternal colonization and invasive disease in infants is necessary to determine the potential coverage of serotype-specific GBS vaccines.Colonizing GBS isolates were identified by vaginal swabbing of mothers during active labor and from skin of their newborns post-delivery. Invasive GBS isolates from infants were identified through laboratory-based surveillance. GBS serotyping was done by latex agglutination. Serologically non-typeable isolates were typed by a serotype-specific PCR method. The invasive potential of GBS serotypes associated with sepsis within seven days of birth was evaluated in association to maternal colonizing serotypes.GBS was identified in 289 (52.4%) newborns born to 551 women with GBS-vaginal colonization and from 113 (5.6%) newborns born to 2,010 mothers in whom GBS was not cultured from vaginal swabs. The serotype distribution among vaginal-colonizing isolates was as follows: III (37.3%), Ia (30.1%), and II (11.3%), V (10.2%), Ib (6.7%) and IV (3.7%). There were no significant differences in serotype distribution between vaginal and newborn colonizing isolates (P = 0.77). Serotype distribution of invasive GBS isolates were significantly different to that of colonizing isolates (P<0.0001). Serotype III was the most common invasive serotype in newborns less than 7 days (57.7%) and in infants 7 to 90 days of age (84.3%; P<0.001). Relative to serotype III, other serotypes showed reduced invasive potential: Ia (0.49; 95%CI 0.31-0.77), II (0.30; 95%CI 0.13-0.67) and V (0.38; 95%CI 0.17-0.83).In South Africa, an anti-GBS vaccine including serotypes Ia, Ib and III has the potential of preventing 74.1%, 85.4% and 98.2% of GBS associated with maternal vaginal-colonization, invasive disease in neonates less than 7 days and invasive disease in infants between 7-90 days of age, respectively

Pneumococcal Serotypes Colonise the Nasopharynx in Children at Different Densities.

Prevalence of pneumococcal serotypes in carriage and disease has been described but absolute serotype colonisation densities have not been reported. 515 paediatric nasal swab DNA extracts were subjected to lytA qPCR and molecular serotyping by microarray. Absolute serotype densities were derived from total pneumococcal density (qPCR cycle threshold and standard curve) and relative abundance (microarray) and varied widely. Compared to all serotype densities observed, the strongest evidence of differences was seen for serotypes 21 and 35B (higher) and 3, 38 and non-typeables (lower) (p<0.05) with a similar hierarchy when only a single serotype carriage was assessed. There was no evidence of any overall density differences between children with single or multiple serotypes detected but serotypes with mid-range densities were more prevalent. The hierarchy of distinct pneumococcal serotype carriage densities described here for the first time, may help explain the dynamics of transmission between children

Impact of Capsular Switch on Invasive Pneumococcal Disease Incidence in a Vaccinated Population

BACKGROUND: Despite the dramatic decline in the incidence of invasive pneumococcal disease (IPD) observed since the introduction of conjugate vaccination, it is feared that several factors may undermine the future effectiveness of the vaccines. In particular, pathogenic pneumococci may switch their capsular types and evade vaccine-conferred immunity. METHODOLOGY/PRINCIPAL FINDINGS: Here, we first review the literature and summarize the available epidemiological data on capsular switch for S. pneumoniae. We estimate the weekly probability that a persistently carried strain may switch its capsule from four studies, totalling 516 children and 6 years of follow-up, at 1.5x10(-3)/week [4.6x10(-5)-4.8x10(-3)/week]. There is not enough power to assess an increase in this frequency in vaccinated individuals. Then, we use a mathematical model of pneumococcal transmission to quantify the impact of capsular switch on the incidence of IPD in a vaccinated population. In this model, we investigate a wide range of values for the frequency of vaccine-selected capsular switch. Predictions show that, with vaccine-independent switching only, IPD incidence in children should be down by 48% 5 years after the introduction of the vaccine with high coverage. Introducing vaccine-selected capsular switch at a frequency up to 0.01/week shows little effect on this decrease; yearly, at most 3 excess cases of IPD per 10(6) children might occur due to switched pneumococcal strains. CONCLUSIONS: Based on all available data and model predictions, the existence of capsular switch by itself should not impact significantly the efficacy of pneumococcal conjugate vaccination on IPD incidence. This optimistic result should be tempered by the fact that the selective pressure induced by the vaccine is currently increasing along with vaccine coverage worldwide; continued surveillance of pneumococcal populations remains of the utmost importance, in particular during clinical trials of the new conjugate vaccines

A Variable Region within the Genome of Streptococcus pneumoniae Contributes to Strain-Strain Variation in Virulence

The bacterial factors responsible for the variation in invasive potential between different clones and serotypes of Streptococcus pneumoniae are largely unknown. Therefore, the isolation of rare serotype 1 carriage strains in Indigenous Australian communities provided a unique opportunity to compare the genomes of non-invasive and invasive isolates of the same serotype in order to identify such factors. The human virulence status of non-invasive, intermediately virulent and highly virulent serotype 1 isolates was reflected in mice and showed that whilst both human non-invasive and highly virulent isolates were able to colonize the murine nasopharynx equally, only the human highly virulent isolates were able to invade and survive in the murine lungs and blood. Genomic sequencing comparisons between these isolates identified 8 regions >1 kb in size that were specific to only the highly virulent isolates, and included a version of the pneumococcal pathogenicity island 1 variable region (PPI-1v), phage-associated adherence factors, transporters and metabolic enzymes. In particular, a phage-associated endolysin, a putative iron/lead permease and an operon within PPI-1v exhibited niche-specific changes in expression that suggest important roles for these genes in the lungs and blood. Moreover, in vivo competition between pneumococci carrying PPI-1v derivatives representing the two identified versions of the region showed that the version of PPI-1v in the highly virulent isolates was more competitive than the version from the less virulent isolates in the nasopharyngeal tissue, blood and lungs. This study is the first to perform genomic comparisons between serotype 1 isolates with distinct virulence profiles that correlate between mice and humans, and has highlighted the important role that hypervariable genomic loci, such as PPI-1v, play in pneumococcal disease. The findings of this study have important implications for understanding the processes that drive progression from colonization to invasive disease and will help direct the development of novel therapeutic strategies

Pneumococcal Capsular Polysaccharide Structure Predicts Serotype Prevalence

There are 91 known capsular serotypes of Streptococcus pneumoniae. The nasopharyngeal carriage prevalence of particular serotypes is relatively stable worldwide, but the host and bacterial factors that maintain these patterns are poorly understood. Given the possibility of serotype replacement following vaccination against seven clinically important serotypes, it is increasingly important to understand these factors. We hypothesized that the biochemical structure of the capsular polysaccharides could influence the degree of encapsulation of different serotypes, their susceptibility to killing by neutrophils, and ultimately their success during nasopharyngeal carriage. We sought to measure biological differences among capsular serotypes that may account for epidemiological patterns. Using an in vitro assay with both isogenic capsule-switch variants and clinical carriage isolates, we found an association between increased carriage prevalence and resistance to non-opsonic neutrophil-mediated killing, and serotypes that were resistant to neutrophil-mediated killing tended to be more heavily encapsulated, as determined by FITC-dextran exclusion. Next, we identified a link between polysaccharide structure and carriage prevalence. Significantly, non-vaccine serotypes that have become common in vaccinated populations tend to be those with fewer carbons per repeat unit and low energy expended per repeat unit, suggesting a novel biological principle to explain patterns of serotype replacement. More prevalent serotypes are more heavily encapsulated and more resistant to neutrophil-mediated killing, and these phenotypes are associated with the structure of the capsular polysaccharide, suggesting a direct relationship between polysaccharide biochemistry and the success of a serotype during nasopharyngeal carriage and potentially providing a method for predicting serotype replacement

Differences in genotype and virulence among four multidrug-resistant <i>Streptococcus pneumoniae</i> isolates belonging to the PMEN1 clone

We report on the comparative genomics and characterization of the virulence phenotypes of four &lt;i&gt;S. pneumoniae&lt;/i&gt; strains that belong to the multidrug resistant clone PMEN1 (Spain&lt;sup&gt;23F&lt;/sup&gt; ST81). Strains SV35-T23 and SV36-T3 were recovered in 1996 from the nasopharynx of patients at an AIDS hospice in New York. Strain SV36-T3 expressed capsule type 3 which is unusual for this clone and represents the product of an in vivo capsular switch event. A third PMEN1 isolate - PN4595-T23 - was recovered in 1996 from the nasopharynx of a child attending day care in Portugal, and a fourth strain - ATCC700669 - was originally isolated from a patient with pneumococcal disease in Spain in 1984. We compared the genomes among four PMEN1 strains and 47 previously sequenced pneumococcal isolates for gene possession differences and allelic variations within core genes. In contrast to the 47 strains - representing a variety of clonal types - the four PMEN1 strains grouped closely together, demonstrating high genomic conservation within this lineage relative to the rest of the species. In the four PMEN1 strains allelic and gene possession differences were clustered into 18 genomic regions including the capsule, the blp bacteriocins, erythromycin resistance, the MM1-2008 prophage and multiple cell wall anchored proteins. In spite of their genomic similarity, the high resolution chinchilla model was able to detect variations in virulence properties of the PMEN1 strains highlighting how small genic or allelic variation can lead to significant changes in pathogenicity and making this set of strains ideal for the identification of novel virulence determinant

Structure and dynamics of the pan-genome of Streptococcus pneumoniae and closely related species

Background Streptococcus pneumoniae is one of the most important causes of microbial diseases in humans. The genomes of 44 diverse strains of S. pneumoniae were analyzed and compared with strains of non-pathogenic streptococci of the Mitis group. Results Despite evidence of extensive recombination, the S. pneumoniae phylogenetic tree revealed six major lineages. With the exception of serotype 1, the tree correlated poorly with capsular serotype, geographical site of isolation and disease outcome. The distribution of dispensable genes, genes present in not all, but more than one strain, was consistent with phylogeny, although horizontal gene transfer events attenuated this correlation in the case of ancient lineages. Homologous recombination, involving short stretches of DNA, was the dominant 13 evolutionary process of the core genome of S. pneumoniae. Genetic exchange occurred both within and across the borders of the species, and S. mitis was the main reservoir of genetic diversity of S. pneumoniae. The pan-genome size of S. pneumoniae increased logarithmically with the number of strains and linearly with the number of polymorphic sites of the sampled genomes, suggesting that acquired genes accumulate proportionately to the age of clones. Most genes associated with pathogenicity were shared by all S. pneumoniae strains, but were also present in S. mitis, S. oralis and S. infantis, indicating that these genes are not sufficient to determine virulence. Conclusion Genetic exchange with related species sharing the same ecological niche is the main mechanism of evolution of S. pneumoniae. The open pan genome guarantees the species a quick and economical response to diverse environments