Rim-to-Rim Wearables at the Canyon for Health (R2R WATCH): Physiological, Cognitive, and Biological Markers of Performance Decline in an Extreme Environment

Success in extreme environments comes with a cost of subtle performance decrements that if not mitigated properly can lead to lifethreatening consequences. Identification and prediction of performance decline could alleviate deleterious consequences and enhance success in challenging and high-risk operations. The Rim-to-Rim Wearables at the Canyon for Health (R2R WATCH) project was designed to examine the cognitive, physiological, and biological markers of performance decline in the extreme environment of the Grand Canyon Rim-to-Rim (R2R) hike. The study utilized commercial off-the-shelf cognitive and physiological monitoring techniques, along with subjective self-assessments and hematologic measurements to determine subject performance and changes across the hike. The multiyear effort collected these multiple data streams in parallel on a large sample of participants hiking the R2R, leading to a rich and complex data set. This article describes the methodology and its evolution as devices and measurements were assessed after each data collection event. It also highlights a subset of the patterns of results found across the data streams. Subsequent work will draw on this data set to focus on building more sophisticated, predictive statistical models and dive deeper into specific analyses (such as the physiological and biological profiles of hikers who were left behind by their hiking partners)

Habitat Fragmentation, Variable Edge Effects, and the Landscape-Divergence Hypothesis

Edge effects are major drivers of change in many fragmented landscapes, but are often highly variable in space and time. Here we assess variability in edge effects altering Amazon forest dynamics, plant community composition, invading species, and carbon storage, in the world's largest and longest-running experimental study of habitat fragmentation. Despite detailed knowledge of local landscape conditions, spatial variability in edge effects was only partially foreseeable: relatively predictable effects were caused by the differing proximity of plots to forest edge and varying matrix vegetation, but windstorms generated much random variability. Temporal variability in edge phenomena was also only partially predictable: forest dynamics varied somewhat with fragment age, but also fluctuated markedly over time, evidently because of sporadic droughts and windstorms. Given the acute sensitivity of habitat fragments to local landscape and weather dynamics, we predict that fragments within the same landscape will tend to converge in species composition, whereas those in different landscapes will diverge in composition. This ‘landscape-divergence hypothesis’, if generally valid, will have key implications for biodiversity-conservation strategies and for understanding the dynamics of fragmented ecosystems

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Formation of Secondary Organic Aerosol by Reactive Condensation of Furandiones, Aldehydes, and Water Vapor Onto Inorganic Aerosol Seed Particles

Volatile furandiones and aldehydes are significant atmospheric oxidation products of aromatic compounds. The mechanism of secondary organic aerosol formation by these compounds was probed using particle chamber observations and macroscale simulations of condensed phases. Growth of inorganic seed aerosol was monitored in the presence of humidity and high concentrations of 2,5-furandione (maleic anhydride), 3-methyl-2,5-furandione (citraconic anhydride), benzaldehyde, and trans-cinnamaldehyde. Particle growth commenced when the gas-phase saturation level of each organic compound and water vapor (relative to its pure liquid), when summed together, reached a threshold near one, implying the formation of a nearly ideal mixed organic/aqueous phase. However, these organics are immiscible with water at the high mole fractions that would be expected in such a phase. Highly acidic dicarboxylic acids produced by the reactions between furandiones and water were shown to rapidly acidify an aqueous phase, resulting in greatly increased benzaldehyde solubility. Thus, the uptake of these organics onto particles in the presence of humidity appears to be reaction-dependent. Finally, it is shown that dicarboxylic acids produced in these reactions recyclize back to furandiones when subjected to normal GC injector temperatures, which could cause large artifacts in gas/particle phase distribution measurements

A workshop on leadership for MD/PhD students

Success in academic medicine requires scientific and clinical aptitude and the ability to lead a team effectively. Although combined MD/PhD training programs invest considerably in the former, they often do not provide structured educational opportunities in leadership, especially as applied to investigative medicine. To fill a critical knowledge gap in physician-scientist training, the Vanderbilt Medical Scientist Training Program (MSTP) developed a biennial two-day workshop in investigative leadership. MSTP students worked in partnership with content experts to develop a case-based curriculum and deliver the material. In its initial three offerings in 2006, 2008, and 2010, the workshop was judged by MSTP student attendees to be highly effective. The Vanderbilt MSTP Leadership Workshop offers a blueprint for collaborative student-faculty interactions in curriculum design and a new educational modality for physician-scientist training

Vesiculovirus Neutralization by Natural IgM and Complement

Because of its very low human seroprevalence, vesicular stomatitis virus (VSV) has promise as a systemic oncolytic agent for human cancer therapy. However, as demonstrated in this report, the VSV infectious titer drops by 4 log units during the first hour of exposure to nonimmune human serum. This neutralization occurs relatively slowly and is mediated by the concerted actions of natural IgM and complement. Maraba virus, whose G protein is about 80% homologous to that of VSV, is relatively resistant to the neutralizing activity of nonimmune human serum. We therefore constructed and rescued a recombinant VSV whose G gene was replaced by the corresponding gene from Maraba virus. Comparison of the parental VSV and VSV with Maraba G substituted revealed nearly identical host range properties and replication kinetics on a panel of tumor cell lines. Moreover, in contrast to the parental VSV, the VSV with Maraba G substituted was resistant to nonimmune human serum. Overall, our data suggest that VSV with Maraba G substituted should be further investigated as a candidate for human systemic oncolytic virotherapy applications. IMPORTANCE Oncolytic virotherapy is a promising approach for the treatment of disseminated cancers, but antibody neutralization of circulating oncolytic virus particles remains a formidable barrier. In this work, we developed a pseudotyped vesicular stomatitis virus (VSV) with a glycoprotein of Maraba virus, a closely related but serologically distinct member of the family Rhabdoviridae, which demonstrated greatly diminished susceptibility to both nonimmune and VSV-immune serum neutralization. VSV with Maraba G substituted or lentiviral vectors should therefore be further investigated as candidates for human systemic oncolytic virotherapy and gene therapy applications