Bench-to-bedside review: Association of genetic variation with sepsis

Susceptibility and response to infectious disease is, in part, heritable. Initial attempts to identify the causal genetic polymorphisms have not been entirely successful because of the complexity of the genetic, epigenetic, and environmental factors that influence susceptibility and response to infectious disease and because of flaws in study design. Potential associations between clinical outcome from sepsis and many inflammatory cytokine gene polymorphisms, innate immunity pathway gene polymorphisms, and coagulation cascade polymorphisms have been observed. Confirmation in large, well conducted, multicenter studies is required to confirm current findings and to make them clinically applicable. Unbiased investigation of all genes in the human genome is an emerging approach. New, economical, high-throughput technologies may make this possible. It is now feasible to genotype thousands of tag single nucleotide polymorphisms across the genome in thousands of patients, thus addressing the issues of small sample size and bias in selecting candidate polymorphisms and genes for genetic association studies. By performing genome-wide association studies, genome-wide scans of nonsynonymous single nucleotide polymorphisms, and testing for differential allelic expression and copy number polymorphisms, we may yet be able to tease out the complex influence of genetic variation on susceptibility and response to infectious disease

Clinical review: Guyton - the role of mean circulatory filling pressure and right atrial pressure in controlling cardiac output

Arthur Guyton's concepts of the determinative role of right heart filling in cardiac output continue to be controversial. This paper reviews his seminal experiments in detail and clarifies the often confusing concepts underpinning his model. One primary criticism of Guyton's model is that the parameters describing venous return had not been measured in a functioning cardiovascular system in humans. Thus, concerns have been expressed in regard to the ability of Guyton's simplistic model, with few parameters, to model the complex human circulation. Further concerns have been raised in regard to the artificial experimental preparations that Guyton used. Recently reported measurements in humans support Guyton's theoretical and animal work

Vasopressin versus norepinephrine infusion in patients with septic shock

Background Vasopressin is commonly used as an adjunct to catecholamines to support blood pressure in refractory septic shock, but its effect on mortality is unknown. We hypothesized that low-dose vasopressin as compared with norepinephrine would decrease mortality among patients with septic shock who were being treated with conventional (catecholamine) vasopressors

Arabidopsis bioinformatics resources: the current state, challenges, and priorities for the future

Effective research, education, and outreach efforts by the Arabidopsis thaliana community, as well as other scientific communities that depend on Arabidopsis resources, depend vitally on easily available and publicly-shared resources. These resources include reference genome sequence data and an ever-increasing number of diverse data sets and data types. TAIR (The Arabidopsis Information Resource) and Araport (originally named the Arabidopsis Information Portal) are community informatics resources that provide tools, data, and applications to the more than 30,000 researchers worldwide that use in their work either Arabidopsis as a primary system of study or data derived from Arabidopsis. Four years after Araport’s establishment, the IAIC held another workshop to evaluate the current status of Arabidopsis Informatics and chart a course for future research and development. The workshop focused on several challenges, including the need for reliable and current annotation, community-defined common standards for data and metadata, and accessible and user-friendly repositories / tools / methods for data integration and visualization. Solutions envisioned included (1) a centralized annotation authority to coalesce annotation from new groups, establish a consistent naming scheme, distribute this format regularly and frequently, and encourage and enforce its adoption. (2) Standards for data and metadata formats, which are essential, but challenging when comparing across diverse genotypes and in areas with less-established standards (e.g. phenomics, metabolomics). Community-established guidelines need to be developed. (3) A searchable, central repository for analysis and visualization tools. Improved versioning and user access would make tools more accessible. Workshop participants proposed a “one-stop shop” website, an Arabidopsis “Super-Portal” to link tools, data resources, programmatic standards, and best practice descriptions for each data type. This must have community buy-in and participation in its establishment and development to encourage adoption