The Contribution of Accessory Toxins of Vibrio cholerae O1 El Tor to the Proinflammatory Response in a Murine Pulmonary Cholera Model

The contribution of accessory toxins to the acute inflammatory response to Vibrio cholerae was assessed in a murine pulmonary model. Intranasal administration of an El Tor O1 V. cholerae strain deleted of cholera toxin genes (ctxAB) caused diffuse pneumonia characterized by infiltration of PMNs, tissue damage, and hemorrhage. By contrast, the ctxAB mutant with an additional deletion in the actin-cross-linking repeats-in-toxin (RTX) toxin gene (rtxA) caused a less severe pathology and decreased serum levels of proinflammatory molecules interleukin (IL)-6 and murine macrophage inflammatory protein (MIP)-2. These data suggest that the RTX toxin contributes to the severity of acute inflammatory responses. Deletions within the genes for either hemagglutinin/protease (hapA) or hemolysin (hlyA) did not significantly affect virulence in this model. Compound deletion of ctxAB, hlyA, hapA, and rtxA created strain KFV101, which colonized the lung but induced pulmonary disease with limited inflammation and significantly reduced serum titers of IL-6 and MIP-2. 100% of mice inoculated with KFV101 survive, compared with 20% of mice inoculated with the ctxAB mutant. Thus, the reduced virulence of KFV101 makes it a prototype for multi-toxin deleted vaccine strains that could be used for protection against V. cholerae without the adverse effects of the accessory cholera toxins

A Population-Based Study of Childhood Cancer Survivors’ Body Mass Index

Background. Population-based studies are needed to estimate the prevalence of underweight or overweight/obese childhood cancer survivors. Procedure. Adult survivors (diagnosed ≤20 years) were identified from the linked Utah Cancer Registry and Utah Population Database. We included survivors currently aged ≥20 years and ≥5 years from diagnosis (N=1060), and a comparison cohort selected on birth year and sex (N=5410). BMI was calculated from driver license data available from 2000 to 2010. Multivariable generalized linear regression models were used to calculate prevalence relative risks (RR) and 95% confidence intervals (95% CI) of BMI outcomes for survivors and the comparison cohort. Results. Average time since diagnosis was 18.5 years (SD=7.8), and mean age at BMI for both groups was 30.5 (survivors SD=7.7, comparison SD=8.0). Considering all diagnoses, survivors were not at higher risk for being underweight or overweight/obese than the comparison. Male central nervous system tumor survivors were overweight (RR=1.12, 95% CI 1.01–1.23) more often than the comparison. Female survivors, who were diagnosed at age 10 and under, had a 10% higher risk of being obese than survivors diagnosed at ages 16–20 (P<0.05). Conclusion. While certain groups of childhood cancer survivors are at risk for being overweight/obese, in general they do not differ from population estimates

Levels of fatigue and distress in senior prostate cancer survivors enrolled in a 12-week randomized controlled trial of Qigong

Fatigue is a commonly reported symptom by prostate cancer survivors and is associated with significant distress and declines in quality of life. Qigong is a mind-body activity that consists of both physical activity and meditative aspects. This 12-week Randomized Controlled Trial (RCT) examined the feasibility and efficacy of a Qigong intervention for improving older prostate cancer survivors’ levels of fatigue and distress

Two integrated and highly predictive functional analysis-based procedures for the classification of MSH6 variants in Lynch syndrome

Purpose: Variants in the DNA mismatch repair (MMR) gene MSH6, identified in individuals suspected of Lynch syndrome, are difficult to classify owing to the low cancer penetrance of defects in that gene. This not only obfuscates personalized health care but also the development of a rapid and reliable classification procedure that does not require clinical data. Methods: The complete in vitro MMR activity (CIMRA) assay was calibrated against clinically classified MSH6 variants and, employing Bayes’ rule, integrated with computational predictions of pathogenicity. To enable the validation of this two-component classification procedure we have employed a genetic screen to generate a large set of inactivating Msh6 variants, as proxies for pathogenic variants. Results: The genetic screen-derived variants established that the two-component classification procedure displays high sensitivities and specificities. Moreover, these inactivating variants enabled the direct reclassification of human variants of uncertain significance (VUS) as (likely) pathogenic. Conclusion: The two-component classification procedure and the genetic screens provide complementary approaches to rapidly and cost-effectively classify the large majority of human MSH6 variants. The approach followed here provides a template for the classification of variants in other disease-predisposing genes, facilitating the translation of personalized genomics into personalized health care

Improvement to the Prediction of Fuel Cost Distributions Using ARIMA Model

Availability of a validated, realistic fuel cost model is a prerequisite to the development and validation of new optimization methods and control tools. This paper uses an autoregressive integrated moving average (ARIMA) model with historical fuel cost data in development of a three-step-ahead fuel cost distribution prediction. First, the data features of Form EIA-923 are explored and the natural gas fuel costs of Texas generating facilities are used to develop and validate the forecasting algorithm for the Texas example. Furthermore, the spot price associated with the natural gas hub in Texas is utilized to enhance the fuel cost prediction. The forecasted data is fit to a normal distribution and the Kullback-Leibler divergence is employed to evaluate the difference between the real fuel cost distributions and the estimated distributions. The comparative evaluation suggests the proposed forecasting algorithm is effective in general and is worth pursuing further.Comment: Accepted by IEEE PES 2018 General Meetin

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Siege of British Forces in Newport County by Colonial and French in August 1778

Funded by a grant from the National Park Service American Battlefield Protection Program, this study delves into the technical, often forgotten, aspects of the Siege of Newport - a Revolutionary War engagement that took place in Middletown, RI in August 1778. It pairs the historical record with scientific analysis of the artillery, fortifications, geography and unforeseen circumstances that impacted the Siege. While much of the original earthen defense-works are now gone, there are a small number of sites that still exist. This study also covers what sites remain, their condition and thoughts on how to preserve and commemorate them.https://digitalcommons.salve.edu/fac_staff_ebooks/1003/thumbnail.jp