Engineering tyrosine-based electron flow pathways in proteins: The case of aplysia myoglobin

Tyrosine residues can act as redox cofactors that provide an electron transfer ("hole-hopping") route that enhances the rate of ferryl heme iron reduction by externally added reductants, for example, ascorbate. Aplysia fasciata myoglobin, having no naturally occurring tyrosines but 15 phenylalanines that can be selectively mutated to tyrosine residues, provides an ideal protein with which to study such through-protein electron transfer pathways and ways to manipulate them. Two surface exposed phenylalanines that are close to the heme have been mutated to tyrosines (F42Y, F98Y). In both of these, the rate of ferryl heme reduction increased by up to 3 orders of magnitude. This result cannot be explained in terms of distance or redox potential change between donor and acceptor but indicates that tyrosines, by virtue of their ability to form radicals, act as redox cofactors in a new pathway. The mechanism is discussed in terms of the Marcus theory and the specific protonation/deprotonation states of the oxoferryl iron and tyrosine. Tyrosine radicals have been observed and quantified by EPR spectroscopy in both mutants, consistent with the proposed mechanism. The location of each radical is unambiguous and allows us to validate theoretical methods that assign radical location on the basis of EPR hyperfine structure. Mutation to tyrosine decreases the lipid peroxidase activity of this myoglobin in the presence of low concentrations of reductant, and the possibility of decreasing the intrinsic toxicity of hemoglobin by introduction of these pathways is discussed. © 2012 American Chemical Society

Quantifying patient satisfaction with process metrics using a weighted bundle approach.

Background:Current patient satisfaction assessment results are delayed and obtained from select patient surveys. As a result, these assessments may not represent the experience of the entire patient population. This study developed a method to measure and evaluate all patients\u27 experiences while they are within the care episode and link it to processes within the organisation. Methods:Using the Six Sigma methodology, sites assembled diverse teams to categorise and analyse negative experience comments from patients to understand the drivers of dissatisfaction. These customer expectations lead to the development of the four components in the Patient Experience Bundle (PEB): communication, environment, basic needs/comfort and logistics. Individual process elements were ranked to create a numerical relationship between service and the needs expressed by the voice of the customer. Sites created surveys incorporating questions that focused on the bundle elements and measured daily bundle compliance. Graphical analysis and hypothesis testing enabled sites to determine key drivers of patient dissatisfaction within the bundle elements. Improvement strategies were developed and implemented to address the key drivers of patient dissatisfaction. Results:After implementing process improvements focused on issues identified by the PEB, bundle compliance improved from an average of 51% to an average of 82.5% and Press Ganey Likelihood to Recommend (PG LTR) scores improved from an average of 64.73% to an average 74.64%. The data demonstrated that the trends in improving PEB are followed by meaningful changes in PG LTR scores. Conclusion:This work is built on the identification of common elements of care that impact patient satisfaction and detailed mathematical analysis of the relationship between factors. Using the bundle concept, these improvement efforts maintain highly reliable processes to drive outcomes and provide real-time feedback on patient experience

Understanding racial differences in health-related quality of life in a population-based cohort of breast cancer survivors

Although racial disparities in health-related quality of life (HRQOL) among women with breast cancer (BC) are well documented, less is known about HRQOL changes over time among women of different races. Our objective was to assess racial differences in HRQOL during active treatment and survivorship phases of BC care

Patient-Centered Communication for Discussing Oncotype DX Testing

Oncotype DX testing (ODX), a tumor gene expression test, may improve breast cancer care, however communicating results remains challenging. We identified patient-centered communication strategies/gaps for discussing ODX results. We applied a patient-centered communication framework to analyze qualitative interviews with oncologists about how they communicate about ODX with patients, using template analysis in Atlas.ti. Overall, providers discussed four patient-centered communication domains: exchanging information, assessing uncertainty, making decisions and cross-cutting themes. Providers did not report discussing emotional aspects of managing uncertainty, assessing decision-making preferences, and evaluating decisions. A patient-centered approach may be a model for communicating about tumor gene expression tests

Racial/Ethnic and Socioeconomic Disparities in Endocrine Therapy Adherence in Breast Cancer: A Systematic Review

We examined the current literature to understand factors that influence endocrine therapy (ET) adherence among racial/ethnic and socioeconomic subpopulations of breast cancer patients. We searched PubMed and PsycINFO databases for studies from January 1, 1978, to June 20, 2014, and January 1, 1991, to June 20, 2014, respectively, and hand-searched articles from relevant literature reviews. We abstracted and synthesized results within a social ecological framework

Half Life of the Doubly-magic r-Process Nucleus 78Ni

Nuclei with magic numbers serve as important benchmarks in nuclear theory. In addition, neutron-rich nuclei play an important role in the astrophysical rapid neutron-capture process (r-process). 78Ni is the only doubly-magic nucleus that is also an important waiting point in the r-process, and serves as a major bottleneck in the synthesis of heavier elements. The half-life of 78Ni has been experimentally deduced for the first time at the Coupled Cyclotron Facility of the National Superconducting Cyclotron Laboratory at Michigan State University, and was found to be 110 (+100 -60) ms. In the same experiment, a first half-life was deduced for 77Ni of 128 (+27 -33) ms, and more precise half-lives were deduced for 75Ni and 76Ni of 344 (+20 -24) ms and 238 (+15 -18) ms respectively.Comment: 4 pages, 3 figure

NACA Technical Notes

Report presenting flight-test measurements and corresponding pilot's opinions of the forward-flight longitudinal flying qualities characteristics of several single-rotor helicopters. The most important consideration for satisfactory characteristics appears to be the prevention of prolonged stick-fixed divergent tendencies. Results regarding the characteristics appreciated, theoretical analysis of pull-up characteristics, and practical requirements are provided

Racial Variation in the Uptake of Onco type DX Testing for Early-Stage Breast Cancer

Oncotype DX (ODX) is a tumor gene-profiling test that aids in adjuvant chemotherapy decision-making. ODX has the potential to improve quality of care; however, if not equally accessible across racial groups, disparities in cancer care quality may persist or worsen. We examined racial disparities in ODX testing uptake