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

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

AMPK:a nutrient and energy sensor that maintains energy homeostasis

AMP-activated protein kinase (AMPK) is a crucial cellular energy sensor. Once activated by falling energy status, it promotes ATP production by increasing the activity or expression of proteins involved in catabolism while conserving ATP by switching off biosynthetic pathways. AMPK also regulates metabolic energy balance at the whole-body level. For example, it mediates the effects of agents acting on the hypothalamus that promote feeding and entrains circadian rhythms of metabolism and feeding behaviour. Finally, recent studies reveal that AMPK conserves ATP levels through the regulation of processes other than metabolism, such as the cell cycle and neuronal membrane excitability

The histone demethylase LSD1 regulates inner ear progenitor differentiation through interactions with Pax2 and the NuRD repressor complex

The histone demethylase LSD1 plays a pivotal role in cellular differentiation, particularly in silencing lineage-specific genes. However, little is known about how LSD1 regulates neurosensory differentiation in the inner ear. Here we show that LSD1 interacts directly with the transcription factor Pax2 to form the NuRD co-repressor complex at the Pax2 target gene loci in a mouse otic neuronal progenitor cell line (VOT-N33). VOT-N33 cells expressing a Pax2-response element reporter were GFP-negative when untreated, but became GFP positive after forced differentiation or treatment with a potent LSD inhibitor. Pharmacological inhibition of LSD1 activity resulted in the enrichment of mono- and di-methylation of H3K4, upregulation of sensory neuronal genes and an increase in the number of sensory neurons in mouse inner ear organoids. Together, these results identify the LSD1/NuRD complex as a previously unrecognized modulator for Pax2-mediated neuronal differentiation in the inner ear

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

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