Transkingdom Networks: A Systems Biology Approach to Identify Causal Members of Host-Microbiota Interactions

Improvements in sequencing technologies and reduced experimental costs have resulted in a vast number of studies generating high-throughput data. Although the number of methods to analyze these "omics" data has also increased, computational complexity and lack of documentation hinder researchers from analyzing their high-throughput data to its true potential. In this chapter we detail our data-driven, transkingdom network (TransNet) analysis protocol to integrate and interrogate multi-omics data. This systems biology approach has allowed us to successfully identify important causal relationships between different taxonomic kingdoms (e.g. mammals and microbes) using diverse types of data

Principles of Glomerular Organization in the Human Olfactory Bulb – Implications for Odor Processing

Olfactory sensory neurons (OSN) in mice express only 1 of a possible 1,100 odor receptors (OR) and axons from OSNs expressing the same odor receptor converge into ∼2 of the 1,800 glomeruli in each olfactory bulb (OB) in mice; this yields a convergence ratio that approximates 2∶1, 2 glomeruli/OR. Because humans express only 350 intact ORs, we examined human OBs to determine if the glomerular convergence ratio of 2∶1 established in mice was applicable to humans. Unexpectedly, the average number of human OB glomeruli is >5,500 yielding a convergence ratio of ∼16∶1. The data suggest that the initial coding of odor information in the human OB may differ from the models developed for rodents and that recruitment of additional glomeruli for subpopulations of ORs may contribute to more robust odor representation

Of gastro and the gold standard: evaluation and policy implications of norovirus test performance for outbreak detection

<p>Abstract</p> <p>Background</p> <p>The norovirus group (NVG) of caliciviruses are the etiological agents of most institutional outbreaks of gastroenteritis in North America and Europe. Identification of NVG is complicated by the non-culturable nature of this virus, and the absence of a diagnostic gold standard makes traditional evaluation of test characteristics problematic.</p> <p>Methods</p> <p>We evaluated 189 specimens derived from 440 acute gastroenteritis outbreaks investigated in Ontario in 2006–07. Parallel testing for NVG was performed with real-time reverse-transcriptase polymerase chain reaction (RT²-PCR), enzyme immunoassay (EIA) and electron microscopy (EM). Test characteristics (sensitivity and specificity) were estimated using latent class models and composite reference standard methods. The practical implications of test characteristics were evaluated using binomial probability models.</p> <p>Results</p> <p>Latent class modelling estimated sensitivities of RT²-PCR, EIA, and EM as 100%, 86%, and 17% respectively; specificities were 84%, 92%, and 100%; estimates obtained using a composite reference standard were similar. If all specimens contained norovirus, RT²-PCR or EIA would be associated with > 99.9% likelihood of at least one test being positive after three specimens tested. Testing of more than 5 true negative specimens with RT²-PCR would be associated with a greater than 50% likelihood of a false positive test.</p> <p>Conclusion</p> <p>Our findings support the characterization of EM as lacking sensitivity for NVG outbreaks. The high sensitivity of RT²-PCR and EIA permit identification of NVG outbreaks with testing of limited numbers of clinical specimens. Given risks of false positive test results, it is reasonable to limit the number of specimens tested when RT²-PCR or EIA are available.</p

Do We Practice What We Preach? A Review of Actual Clinical Practice with Regards to Preconception Care Guidelines

Objectives: To review what past studies have found with regard to existing clinical practices and approaches to providing preconception care. Methods: A literature review between 1966 and September 2005 was performed using Medline. Key words included preconception care, preconception counseling, preconception surveys, practice patterns, pregnancy outcomes, prepregnancy planning, and prepregnancy surveys. Results: There are no current national recommendations that fully address preconception care; as a result, there is wide variability in what is provided clinically under the rubric of preconception care. Conclusions: In 2005, the Centers for Disease Control and Prevention sponsored a national summit regarding preconception care and efforts are underway to develop a uniform set of national recommendations and guidelines for preconception care. Understanding how preconception care is presently incorporated and manifested in current medical practices should help in the development of these national guidelines. Knowing where, how, and why some specific preconception recommendations have been successfully adopted and translated into clinical practice, as well as barriers to implementation of other recommendations or guidelines, is vitally important in developing an overarching set of national guidelines. Ultimately, the success of these recommendations rests on their ability to influence and shape women's health policy

Predictors of Breast and Cervical Cancer Screening among Chamorro Women in Southern California

This study examined the role of sociodemographic characteristics, health insurance, cancer knowledge, perceived health risk, and having a recent physicians’ visit on breast and cervical cancer screening utilization among a randomly selected group of Chamorro women (n = 250) residing in San Diego, California. Data were collected by a telephone survey and analyzed using multiple logistic regression models. After adjusting for covariates, having a recent full exam was the strongest predictor of having had a Pap exam in the past 2 years for women 21 years and older and a clinical breast exam in the past 2 years for women 40 years and over

Collaborative research between clinicians and researchers: a multiple case study of implementation

<p>Abstract</p> <p>Background</p> <p>Bottom-up, clinician-conceived and directed clinical intervention research, coupled with collaboration from researcher experts, is conceptually endorsed by the participatory research movement. This report presents the findings of an evaluation of a program in the Veterans Health Administration meant to encourage clinician-driven research by providing resources believed to be critical. The evaluation focused on the extent to which funded projects: maintained integrity to their original proposals; were methodologically rigorous; were characterized by collaboration between partners; and resulted in sustained clinical impact.</p> <p>Methods</p> <p>Researchers used quantitative (survey and archival) and qualitative (focus group) data to evaluate the implementation, evaluation, and sustainability of four clinical demonstration projects at four sites. Fourteen research center mentors and seventeen clinician researchers evaluated the level of collaboration using a six-dimensional model of participatory research.</p> <p>Results</p> <p>Results yielded mixed findings. Qualitative and quantitative data suggested that although the process was collaborative, clinicians' prior research experience was critical to the quality of the projects. Several challenges were common across sites, including subject recruitment, administrative support and logistics, and subsequent dissemination. Only one intervention achieved lasting clinical effect beyond the active project period. Qualitative analyses identified barriers and facilitators and suggested areas to improve sustainability.</p> <p>Conclusions</p> <p>Evaluation results suggest that this participatory research venture was successful in achieving clinician-directed collaboration, but did not produce sustainable interventions due to such implementation problems as lack of resources and administrative support.</p

The Complete Genome Sequence of the Pathogenic Intestinal Spirochete Brachyspira pilosicoli and Comparison with Other Brachyspira Genomes

Background: The anaerobic spirochete Brachyspira pilosicoli colonizes the large intestine of various species of birds and mammals, including humans. It causes ''intestinal spirochetosis'', a condition characterized by mild colitis, diarrhea and reduced growth. This study aimed to sequence and analyse the bacterial genome to investigate the genetic basis of its specialized ecology and virulence. Methodology/Principal Findings: The genome of B. pilosicoli 95/1000 was sequenced, assembled and compared with that of the pathogenic Brachyspira hyodysenteriae and a near-complete sequence of Brachyspira murdochii. The B. pilosicoli genome was circular, composed of 2,586,443 bp with a 27.9 mol% G+C content, and encoded 2,338 genes. The three Brachyspira species shared 1,087 genes and showed evidence of extensive genome rearrangements. Despite minor differences in predicted protein functional groups, the species had many similar features including core metabolic pathways. Genes distinguishing B. pilosicoli from B. hyodysenteriae included those for a previously undescribed bacteriophage that may be useful for genetic manipulation, for a glycine reductase complex allowing use of glycine whilst protecting from oxidative stress, and for aconitase and related enzymes in the incomplete TCA cycle, allowing glutamate synthesis and function of the cycle during oxidative stress. B. pilosicoli had substantially fewer methyl-accepting chemotaxis genes than B. hyodysenteriae and hence these species are likely to have different chemotactic responses that may help to explain their different host range and colonization sites. B. pilosicoli lacked the gene for a new putative hemolysin identified in B. hyodysenteriae WA1. Both B. pilosicoli and B. murdochii lacked the rfbBADC gene cluster found on the B. hyodysenteriae plasmid, and hence were predicted to have different lipooligosaccharide structures. Overall, B. pilosicoli 95/1000 had a variety of genes potentially contributing to virulence. Conclusions/Significance: The availability of the complete genome sequence of B. pilosicoli 95/1000 will facilitate functional genomics studies aimed at elucidating host-pathogen interactions and virulence

A blended knowledge translation initiative to improve colorectal cancer staging [ISRCTN56824239]

BACKGROUND: A significant gap has been documented between best practice and the actual practice of surgery. Our group identified that colorectal cancer staging in Ontario was suboptimal and subsequently developed a knowledge translation strategy using the principles of social marketing and the influence of expert and local opinion leaders for colorectal cancer. METHODS/DESIGN: Opinion leaders were identified using the Hiss methodology. Hospitals in Ontario were cluster-randomized to one of two intervention arms. Both groups were exposed to a formal continuing medical education session given by the expert opinion leader for colorectal cancer. In the treatment group the local Opinion Leader for colorectal cancer was detailed by the expert opinion leader for colorectal cancer and received a toolkit. Forty-two centres agreed to have the expert opinion leader for colorectal cancer come and give a formal continuing medical education session that lasted between 50 minutes and 4 hours. No centres refused the intervention. These sessions were generally well attended by most surgeons, pathologists and other health care professionals at each centre. In addition all but one of the local opinion leaders for colorectal cancer met with the expert opinion leader for colorectal cancer for the academic detailing session that lasted between 15 and 30 minutes. DISCUSSION: We have enacted a unique study that has attempted to induce practice change among surgeons and pathologists using an adapted social marketing model that utilized the influence of both expert and local opinion leaders for colorectal cancer in a large geographic area with diverse practice settings

The South, the suburbs, and the Vatican too: explaining partisan change among Catholics

This paper explains changes in partisanship among Catholics in the last quarter of the 20th Century using a theory of partisan change centered on the contexts in which Catholics lived. Catholics were part of the post-New Deal Democratic coalition, but they have become a swing demographic group. We argue that these changes in partisanship are best explained by changes in elite messages that are filtered through an individual’s social network. Those Catholics who lived or moved into the increasingly Republican suburbs and South were the Catholics who were most likely to adopt a non-Democratic partisan identity. Changes in context better explain Catholic partisanship than party abortion policy post Roe v. Wade or ideological sorting. We demonstrate evidence in support of our argument using the ANES cumulative file from 1972 through 2000