Nutrition Derived Advanced Glycation End Products Are Bio-Social Determinants of Health That Inform on Cancer Disparities

Objectives Through their ability to perpetuate a reactive stroma, the objective was to define the increased nutritional bioavailability of advanced glycation end products (AGEs) as a pro-tumorigenic consequence of interrelated health inequity risk factors that can influence ancestry specific tumor biology. Methods In vivo, ex vivo, and in vitro models were used to define the molecular effects of nutrition associated AGEs on the ancestry specific tumor microenvironment and tumor growth. Results The PI’s work provides the first in vivo evidence supporting an oncogenic role for AGEs. In mouse allograft models, both the chronic consumption of AGEs and pre-treatment with AGE bound peptide (p\u3c 0.0001) increased prostate tumor growth. In spontaneous tumor models, chronic AGE consumption caused rapid disease progression through prostate intra-epithelial neoplasia (p=0.049) to adenocarcinoma and metastatic disease. Mechanistically, AGEs recapitulated a regulatory program of ‘activated’ stroma similar to that observed in African American prostate tumors. Specifically, increased AGE bioavailability caused receptor for AGE (RAGE) dimerization in resident PCa fibroblasts leading to their activation and the downregulation of matrix regulatory proteins leading to rapid tumor progression. Conclusions When social and biological determinants of health are compromised it may increase nutritional exposure to AGEs and perpetuate a vicious cycle of AGE formation, bioavailability, and pathogenicity. As bio-social determinants of health, AGEs may represent informative and/or functional biomarkers that can be utilized across transdisciplinary studies to address the enduring complexities of cancer disparity

F-18 high alpha research vehicle: Lessons learned

The F-18 High Alpha Research Vehicle has proven to be a useful research tool with many unique capabilities. Many of these capabilities are to assist in characterizing flight at high angles of attack, while some provide significant research in their own right. Of these, the thrust vectoring system, the unique ability to rapidly reprogram flight controls, the reprogrammable mission computer, and a reprogrammable onboard excitation system have allowed an increased utility and versatility of the research being conducted. Because of this multifaceted approach to research in the high angle of attack regime, the capabilities of the F-18 High Alpha Research Vehicle were designed to cover as many high alpha technology bases as the program would allow. These areas include aerodynamics, controls, handling qualities, and propulsion

Development of a multilocus sequence typing scheme for the molecular typing of Mycoplasma pneumoniae

This work was funded by Public Health England. These studies were supported by funding initiatives by the National Institute for Social Care and Health Research (NISCHR; research support from the Welsh Government) via the registered research group Microbial and Infection Translational Research Group (MITReG) and Children and Young Persons Research Network (CYPRN).Mycoplasma pneumoniae is a major human respiratory pathogen causing both upper and lower respiratory disease in humans of all ages, and it can also result in other serious extrapulmonary sequelae. A multilocus sequence typing (MLST) scheme for M. pneumoniae was developed based on the sequences of eight housekeeping genes (ppa, pgm, gyrB, gmk, glyA, atpA, arcC, and adk) and applied to 55 M. pneumoniae clinical isolates and the two type strains M129 and FH. A total of 12 sequence types (STs) resulted for 57 M. pneumoniae isolates tested, with a discriminatory index of 0.21 STs per isolate. The MLST loci used in this scheme were shown to be stable in 10 strains following 10 sequential subculture passages. Phylogenetic analysis of concatenated sequences of the eight loci indicated two distinct genetic clusters that were directly linked to multilocus variable-number tandem repeat analysis (MLVA) type. Genetic MLST clustering was confirmed by genomic sequence analysis, indicating that the MLST scheme developed in this study is representative of the genome. Furthermore, this MLST scheme was shown to be more discriminatory than both MLVA and P1 typing for the M. pneumoniae isolates examined, providing a method for further and more detailed analysis of observed epidemic peaks of M. pneumoniae infection. This scheme is supported by a public Web-based database (http://pubmlst.org/mpneumoniae).PostprintPeer reviewe

Responsiveness of a 1-year recall modified DASH Work module in active workers with upper extremity musculoskeletal symptoms

OBJECTIVES: To evaluate the responsiveness to change of a modified version of the Work module of the Disabilities of the Arm, Shoulder, and Hand (DASH-W) in a prospective, longitudinal cohort study of active workers. METHODS: We compared change on a 1-year recall modified DASH-W to change on work ability, work productivity, and symptom severity, according to predetermined hypotheses following the Consensus-based standards for the selection of health measurement instruments (COSMIN). We evaluated concordance in the direction of change, and magnitude of change using Spearman rank correlations, effect sizes (ES), standardized response means (SRM), and area under the receiver operating characteristic curves (AUC). RESULTS: In a sample of 551 workers, change in 1-year recall modified DASH-W scores showed moderate correlations with changes in work ability, work productivity, and symptom severity (r=0.47, 0.44, and 0.36, respectively). ES and SRM were moderate for 1-year recall modified DASH-W scores in workers whose work ability (ES=−0.58, SRM=−0.52) and work productivity improved (ES=−0.59, SRM=−0.56), and larger for workers whose work ability (ES=1.24, SRM=0.68) and work productivity worsened (ES=1.02, SRM=0.61). ES and SRM were small for 1-year recall modified DASH-W scores of workers whose symptom severity improved (−0.32 and −0.29, respectively). Responsiveness of the 1-year recall modified DASH-W was moderate for those whose symptom severity worsened (ES=0.77, SRM=0.50). AUC met responsiveness criteria for work ability and work productivity. CONCLUSIONS: The 1-year recall modified DASH-W is responsive to changes in work ability and work productivity in active workers with upper extremity symptoms

Design and Integration of an Actuated Nose Strake Control System

Aircraft flight characteristics at high angles of attack can be improved by controlling vortices shed from the nose. These characteristics have been investigated with the integration of the actuated nose strakes for enhanced rolling (ANSER) control system into the NASA F-18 High Alpha Research Vehicle. Several hardware and software systems were developed to enable performance of the research goals. A strake interface box was developed to perform actuator control and failure detection outside the flight control computer. A three-mode ANSER control law was developed and installed in the Research Flight Control System. The thrust-vectoring mode does not command the strakes. The strakes and thrust-vectoring mode uses a combination of thrust vectoring and strakes for lateral- directional control, and strake mode uses strakes only for lateral-directional control. The system was integrated and tested in the Dryden Flight Research Center (DFRC) simulation for testing before installation in the aircraft. Performance of the ANSER system was monitored in real time during the 89-flight ANSER flight test program in the DFRC Mission Control Center. One discrepancy resulted in a set of research data not being obtained. The experiment was otherwise considered a success with the majority of the research objectives being met