The measurement, biological variation and response to acute inflammation of asymmetric dimethylarginine (ADMA)

Introduction and methods Asymmetric dimethylarginine (ADMA) is a potent endogenous competitive inhibitor of nitric oxide synthases, which has attracted considerable attention as a marker and mediator of atherosclerotic disease and as a potential mediator of multiple organ failure in critical illness due to endothelial dysfunction. However, data regarding basic aspects of its biology such as biological variation and its response to acute inflammation are lacking. Moreover, significant methodological variability has been a barrier to collating the burgeoning data available. Therefore, this thesis describes the development and validation of a reliable assay for measurement of ADMA and related compounds in plasma, urine and other biological fluids based on isocratic reverse phase high performance liquid chromatography (HPLC). This method was used to determine the biological variation of ADMA in human plasma, and its response to acute inflammation using a model of elective knee arthroplasty. Further HPLC methods for measurement of dimethylamine (DMA), the main metabolite of ADMA, and nitrate were developed and used to determine excretion of these compounds in acute inflammation to complement the observed changes in plasma ADMA concentration. Results Complete chromatographic separation of arginine, homoarginine, monomethyl-arginine, ADMA and its structural isomer SDMA was achieved, permitting their accurate quantification using a novel, non-endogenous, internal standard. The intra-individual biological variation of ADMA was found to be low at 7.4%, imposing a tight imprecision goal for analytical methods. Plasma ADMA concentration decreases rapidly during the acute inflammatory response, with a median decrease of around 30%, and a significant change already evident as little as 12 hours following the onset of inflammation. No similar change was seen in the concentration of the closely related compound SDMA. No significant increase in the urine excretion of DMA was noted during the early phase of the response, with a significant increase seen 5 days following the insult by which point the plasma ADMA concentration had returned to baseline levels. A small, but significant, decrease in nitrate excretion during the inflammatory response was seen, mirroring the observed changes in plasma ADMA. Conclusion The low biological variation of ADMA suggests physiological regulation. The rapid and significant decrease in plasma concentration during inflammation does not appear due to increased catabolism, but rather is more likely to represent increased cellular partitioning. This may be associated with an impairment in NOS activity. It is unclear whether this is of pathological significance, or represents a physiological response to regulate NO production in inflammation. Further study is warranted in relevant models, particularly with attention to intracellular concentrations

Analysis of Flow From Arc-Jet Spectra

Materials testing is carried out at the JSC Atmospheric Reentry Materials and Structures Facility. A flow diagnostics program is under development to characterize the energy distribution in arc-jet flows used to simulate atmospheric entry. Heat transfer to materials depends on flow properties which includes the composition of and energy distribution among the atoms, ions, molecules, and molecular ions which make up the flow. This project involves analysis of shock layer characteristics from the radiation emitted and experimentally collected from near the front of the shock to near the surface of the material. The analysis has yielded information on relative populations of neutral molecules and molecular ions within the layer. In determining non-equilibrium temperatures within the layer, some insight into the spectral constants used to compute radiative emission has been gained

A study of the perceived leadership orientations of selected leaders and members of the Corps of Cadets at Texas A&M University through application of the Competing Values Framework

The purpose of this study was to examine the perceived leadership orientations of leaders and general members affiliated with the Corps of Cadets at Texas A&M University, assess the validity and reliability for the Competing Values Instrument for the cadet population, and identify differences in leadership orientations of leaders and members of a student organization. The survey instrument used was an adaptation of Quinn's 1988 Competing Values Instrument. The two-part 32-item instrument was theoretically based on Quinn and Rohrbaugh's (1981, 1983) Competing Values Framework of managerial-leadership. The instrument divided the items into eight groups of leadership role orientations: Innovator, Broker, Producer, Director, Coordinator, Monitor, Facilitator, and Mentor. The instrument was administered to 520 cadets enrolled in 28 randomly selected Reserve Officers' Training Corps (ROTC) and School of Military Science (SOMS) courses at Texas A&M University. Responses were compared using various background information and environmental factors. Responses were also examined to establish validity and reliability for the instrument when used with college student members of this student organization. Factor analysis procedures resulted in slight alteration of items within specific factors. Results supported the idea that perceived leadership orientations are associated with academic classification, Corps classification, gender, age, leadership experience prior to college, involvement in college leadership experiences other than the Corps of Cadets, contract status, level of leadership position in the student organization, and military service affiliation. The contributions the student organization made to the development of leadership were assessed, and a better understanding of leaders' and members' perceptions of their leadership tendencies and practices was obtained. Survey instrument data indicated the Corps of Cadets was effective in enhancing students' perceptions of their leadership orientations. Recognizable differences were found to have existed in relationship to the complexity and nature of the leadership position. The higher the level of leadership position held by members of the Corps of Cadets, the more frequent those members' practice of leadership and management behaviors became. Military cadets were also more likely to practice leadership and management behaviors more frequently than non-military cadets. The study provided evidence that the Corps of Cadets has some effect on leadership development

Recommended Joint and Meta‐Analysis Strategies for Case‐Control Association Testing of Single Low‐Count Variants

In genome‐wide association studies of binary traits, investigators typically use logistic regression to test common variants for disease association within studies, and combine association results across studies using meta‐analysis. For common variants, logistic regression tests are well calibrated, and meta‐analysis of study‐specific association results is only slightly less powerful than joint analysis of the combined individual‐level data. In recent sequencing and dense chip based association studies, investigators increasingly test low‐frequency variants for disease association. In this paper, we seek to (1) identify the association test with maximal power among tests with well controlled type I error rate and (2) compare the relative power of joint and meta‐analysis tests. We use analytic calculation and simulation to compare the empirical type I error rate and power of four logistic regression based tests: Wald, score, likelihood ratio, and Firth bias‐corrected. We demonstrate for low‐count variants (roughly minor allele count [MAC] < 400) that: (1) for joint analysis, the Firth test has the best combination of type I error and power; (2) for meta‐analysis of balanced studies (equal numbers of cases and controls), the score test is best, but is less powerful than Firth test based joint analysis; and (3) for meta‐analysis of sufficiently unbalanced studies, all four tests can be anti‐conservative, particularly the score test. We also establish MAC as the key parameter determining test calibration for joint and meta‐analysis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99692/1/gepi21742.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99692/2/gepi21742-sup-0010-figureS1.pd

Assessment of the quality of online patient information resources for patients considering parastomal hernia treatment

Aim: The aim was to examine the quality of online patient information resources for patients considering parastomal hernia treatment.Methods: A Google search was conducted using lay search terms for patient facing sources on parastomal hernia. The quality of the content was assessed using the validated DISCERN instrument. Readability of written content was established using the Flesch–Kincaid score. Sources were also assessed against the essential content and process standards from the National Institute for Health and Care Excellence (NICE) framework for shared decision making support tools. Content analysis was also undertaken to explore what the sources covered and to identify any commonalities across the content.Results: Fourteen sources were identified and assessed using the identified tools. The mean Flesch–Kincaid reading ease score was 43.61, suggesting that the information was difficult to read. The overall quality of the identified sources was low based on the pooled analysis of the DISCERN and Flesch–Kincaid scores, and when assessed against the criteria in the NICE standards framework for shared decision making tools. Content analysis identified eight categories encompassing 59 codes, which highlighted considerable variation between sources.Conclusions: The current information available to patients considering parastomal hernia treatment is of low quality and often does not contain enough information on treatment options for patients to be able to make an informed decision about the best treatment for them. There is a need for high-quality information, ideally co-produced with patients, to provide patients with the necessary information to allow them to make informed decisions about their treatment options when faced with a symptomatic parastomal hernia

An Overview of NASA TROPICS Applications and Early Adopter Activities

No abstract availabl

Effect of Plasma Flux Composition on the Nitriding Rate of Stainless Steel

The total ion flux and nitriding rate for stainless steel specimens exposed to a modulated electron beam generated argon-nitrogen plasma were measured as a function of distance from the electron beam axis. The total ion flux decreased linearly with distance, but the nitriding rate increased under certain conditions, contrary to other ion flux/nitriding rate comparisons published in the literature. Variation in ion flux composition with distance was explored with a mass spectrometer and energy analyzer as a possible explanation for the anomalous nitriding rate response to ion flux magnitude. A transition in ion flux composition from mostly N2 1 to predominantly N1 ions with increasing distance was observed. Significant differences in molecular and atomic nitrogen ion energy distributions at a negatively biased electrode were also measured. An explanation for nitriding rate dependence based on flux composition and magnitude is proposed

DEFINING AND REDUCING WILDLIFE HAZARDS TO AVIATION IN THE USA

The U.S. Department of Agriculture’s National Wildlife Research Center (NWRC), through an interagency agreement with the U.S. Federal Aviation Administration (FAA), conducts a national research program to define and reduce bird and other wildlife hazards to aircraft. The goal is to provide the FAA and airports nationwide with a scientific foundation for policies and recommendations related to wildlife and aviation safety. Research tasks conducted by NWRC under the agreement include: 1) investigations of habitat management and land-use practices on and near airports to reduce bird activity; 2) development and evaluation of bird repellent and frightening methods for airports; 3) management and analysis of the National Wildlife Strike Database for civil aviation; and 4) development of publications, including a manual on wildlife hazard management, for use by airport operators nationwide. The research, coordinated by NWRC’s Sandusky, Ohio Field Station, has resulted in over 100 scientific publications since 1992. Recent highlights include 1) development of a wildlife strike database for civil aviation with about 28,000 strike reports, 1990-1999; 2) publication of a report, based on analyses of data in the bird strike database, which indicated wildlife collisions with aircraft cost U.S. civil aviation over $300 million/year, 1990-1998; 3) partnership with private industry to develop chemical repellents for use against Canada geese on airports; 4) development of management program at JFK International Airport, New York, that resulted in a 90% reduction in gull-aircraft collisions; and 5) publication of a comprehensive manual for airport personnel entitled “Wildlife Hazard Management at Airports”

Atomistic surface erosion and thin film growth modelled over realistic time scales

We present results of atomistic modelling of surface growth and sputtering using a multi-time scale molecular dynamics–on-the-fly kinetic Monte Carlo scheme which allows simulations to be carried out over realistic experimental times. The method uses molecular dynamics to model the fast processes and then calculates the diffusion barriers for the slow processes on-the-fly, without any preconceptions about what transitions might occur. The method is applied to the growth of metal and oxide materials at impact energies typical for both vapour deposition and magnetron sputtering. The method can be used to explain growth processes, such as the filling of vacancies and the formation of stacking faults. By tuning the variable experimental parameters on the computer, a parameter set for optimum crystalline growth can be determined. The method can also be used to model sputtering where the particle interactions with the surface occur at a higher energy. It is shown how a steady state can arise in which interstitial clusters are continuously being formed below the surface during an atom impact event which also recombine or diffuse to the surface between impact events. For fcc metals the near surface region remains basically crystalline during the erosion process with a pitted topography which soon attains a steady state roughness