Optimizing heart dose reduction for deep inspiration left breast radiotherapy

Multiple studies have shown that an increased risk of late injury cardiac abnormalities including congestive heart failure (CHF), ischemia, and coronary artery disease (CAD) can be associated with common left breast radiation therapy (RT) techniques. Many radiation therapy clinics have adopted the Deep Inspiration Breath Hold (DIBH) technique for the treatment of the left breast with external beam therapy based on studies showing a decrease in the dose received by the heart. A common technology used to monitor inhalation during DIBH is the Real-Time Position Management (RPM) system (Varian Medical Systems, Palo Alto, CA). This study analyzes if there is an optimal setup protocol for the use of the RPM system in order to minimize heart dose during DIBH RT of the left breast

Sex-based differences in microbiota composition and metabolomic profiles associated with altered macrophage function and protection from lupus in BWF1 mice.

Systemic lupus erythematosus (SLE) is a complex and an insidious disease that is still not completely understood, and has very few treatment options. Those that are available are ineffective and/or have serious side effects. Both genetic and environmental factors contribute to the susceptibility and resistance to SLE, and understanding the environmental factors underlying this disease could lead to more effective prevention and/or treatment strategies. Like most autoimmune diseases, SLE is much more prevalent in females than males. While there are numerous factors that contribute to this lupus susceptibility, there is increasing evidence that the microbiota can strongly influence lupus progression, and that sex-based differences in microbiota composition and function may play a role in the sex bias (i.e., susceptibility in females and resistance in males) of disease. The NZBxNZW F1 (BWF1) mouse model of lupus has many of the same disease features seen in humans including the sex bias, making it an ideal model for studying sex-based differences in microbiota and how they affect lupus progression. Previous findings from our laboratory have shown that not only do female and male BWF1 microbiota profiles differ significantly, but male BWF1 microbiota can suppress lupus when cecal contents are transferred into female BWF1 recipients. The overall goal of this dissertation was to identify the players involved and begin to understand the potential mechanisms underlying the suppressive effect of the male microbiota on disease. Three aims were designed to address these issues. The goal of aim 1 was to identify the bacterial populations in the microbiota of female and male BWF1 mice that may either cause or suppress disease. The goal of aim 2 was to analyze the function of female and male microbiota by identifying metabolites that may be involved in the suppression of disease. In aims 1 and 2, we also investigated the impact of androgens on bacterial populations and metabolite profiles, respectively, by comparing intact and castrated male mice. In aim 3, the goal was to investigate the potential immune mechanisms that could underlie the suppression of disease mediated by male microbiota. The results of the first aim indicate that changes in the abundances of Bacteroides, Clostridium, and Alistipes strongly correlated with the ability of transferred male BWF1 microbiota to suppress disease in female BWF1 recipients. We took advantage of a change in animal facility that had a significant impact on our mouse colony and its microbiota populations, and gave us an opportunity to analyze and compare bacterial populations during periods of time when microbiota transfers had varying results. Specifically, we found that Bacteroides (primarily the Bacteroides acidifaciens species) abundance was high, Clostridium (primarily the Clostridium leptum species) abundance was low, and Alistipes was present during the periods when transfer of male microbiota was effective at suppressing disease in female BWF1 mice. Conversely, Bacteroides abundance was low, Clostridium abundance was high, and Alistipes was absent when male microbiota lost that capability. We concluded from our thorough microbiota analyses that a high Bacteroides/Clostridium ratio in the male microbiota may be a reliable predictor of disease-suppressing capability, since it correlated strongly with disease suppression in female recipients of male microbiota. The second aim of the project used analysis of metabolomic profiles to investigate functional differences in female and male BWF1 microbiota. Differential production of immunomodulatory metabolites is a major mechanism by which the gut microbiota influences the immune system. By measuring the fecal metabolite profiles, we identified phytol as a potential mediator of lupus suppression by male microbiota. Phytol is produced by the microbiota and converted into phytanic acid by host enzymes. Both phytol and phytanic acid were significantly more abundant in intact male than either female or castrated male BWF1 mice. Both phytol and phytanic acid have potent RXR and PPARγ agonist properties, all of which can directly influence many different immune functions. The third aim of this project investigated the differences in female and male macrophage efferocytosis (i.e., phagocytosis of apoptotic cells) efficacy and how phytol and/or phytanic acid could affect this immune function. Deficiencies in efferocytosis, particularly by macrophages, are a major risk factor for SLE because they result in the accumulation of debris that stimulates autoantibody production. We found male BWF1 splenic macrophages were more efficient at efferocytosis than female splenic macrophages, and treatment with phytanic acid in vitro or in vivo could enhance female splenic macrophage efferocytosis. Overall, we found that higher Bacteroides and lower Clostridium abundances correlated with lupus suppression in female BWF1 recipients of male microbiota, and speculate that this protection could be due, at least in part, to higher levels of phytol and phytanic acid production in males. Furthermore, phytol and phytanic acid produced by males may suppress disease, again at least in part, via enhancement of macrophage efferocytosis. Taken together, these data may provide the basis for a mechanistic understanding of the impact that the microbiota can have on autoimmune diseases such as lupus, and for the development of novel therapies

A Study of Fringe Benefits Available to Non-Professional Employees of Community Unit School Districts in Illinois

No abstract provided by author

Exploring Environmental Racism, Quality of Life, and Inequalities in Kentucky Counties

Environmental racism explores how pollution-producing industries are systematically constructed in and around poor, minority communities. Exposure to pollutants over time negatively impacts resident well being and quality of life while economic trends limit opportunities to relocated. Kentucky provides a valuable opportunity for exploring environmental racism. The state’s long dependency on coal extraction has created environmental opportunities for studying this phenomenon amid deindustrialization throughout the region. This study examines how changes in air pollution (a proxy measure of environmental toxins) correlates to poverty, quality of life, and resident racial demographics. Results indicate that Kentucky counties with higher air pollution had lower poverty and higher quality of life overall while having a lower percentage of white residents. These findings offer an unexpected new perspective on the conflicting relationship between increased economic development, declining poverty, and increased quality of life amid concerns over the creation of environmental pollutants

Oxidative durability of TBCs on Ti\u3csub\u3e2\u3c/sub\u3eAlC MAX phase substrates

Air plasma spray (APS) and plasma-spray-physical vapor deposition (PS-PVD) yttria-stabilized zirconia (YSZ) thermal barrier coatings (TBC), ~80–100 μm thick, were produced on a commercial Ti2AlC MAX phase compound. They were oxidized in interrupted furnace tests for 500 h each, at five successive temperatures from 1100°–1300 °C. The APS coating survived 2400 accumulated hours, failing catastrophically after 500 h at 1300°C. Porosity, large cracks, sintering, and high monoclinic YSZ phase contents were seen as primary degradation factors. The PS-PVD coating remained completely intact over 2500 total hours (65 cycles) including 500 h at 1300 °C, exhibiting only fine porosity and microcracking, with less monoclinic. These Ti2AlC systems achieved aminimumα-Al2O3 scale thickness of 29 and 35 μm, respectively, as compared to ~6±2 μmon average at failure for conventional bond coats on superalloys. Accordingly, times predicted from thermogravimetric analyses (TGA) of oxidation kinetics project an improvement factor of ~25–50× for the time to achieve these scale thicknesses at a given temperature. Extreme oxidative TBC durability is achieved because the thermal expansion coefficient of Ti2AlC is only slightly different than those for α-Al2O3 and YSZ. The strain energy term driving scale and TBC failure is therefore believed to be fundamentally diminished fromthe large compressive stress produced by higher expansion superalloys

An Examination of Trinidadian Officer\u27s Behavioral Beliefs and Intent to Participate in an International Extension Experience

Participation in an international extension experience empowers extension professionals to meet the needs of diverse clientele in an increasingly global world. A survey of governmental extension workers in Trinidad was conducted to understand how their behavioral beliefs about an international extension experience influenced their intention to participate in such an experience. Behavioral beliefs can be positively or negatively modified based on an individual’s perceptions of the components (time, location, activities) of a specific international extension experience, so manipulating the components should cause corresponding changes in behavioral beliefs and ultimately intent to participate. This study found positive behavioral beliefs about international extension experience participation are held by Trinidadian extension officers. They are willing to travel to a wide variety of locations and are most interested in acquiring hands-on experience and working one-on-one with another extension professional. The most desirable locations and activities should be integrated into international extension experiences in order to positively influence behavioral beliefs, and thereby intent to participate. Future research is needed to more closely examine the impact of participation on extension officers in Trinidad

An Assessment of Extension Officers’ Self-Perceived Programming Competencies in Selected Caribbean Countries

Developing the human capacity of extension systems is a necessary part of improving services intended to meet the needs of small farmers. The purpose of this study was to determine the competencies for which professional development is needed in the area of programming for extension officers in selected Caribbean countries. A survey was conducted with all extension officers attending in-service trainings in Belize, Grenada, and Saint Lucia, using the Borich method to identify priority training needs. The greatest needs were most frequently observed in the areas of program planning and evaluation, although considerable variation existed across the group. The resulting challenge is to develop professional development resources that can be individualized by country while remaining cost-effective and accessibl

PRECEPT: an evidence assessment framework for infectious disease epidemiology, prevention and control

Decisions in public health should be based on the best available evidence, reviewed and appraised using a rigorous and transparent methodology. The Project on a Framework for Rating Evidence in Public Health (PRECEPT) defined a methodology for evaluating and grading evidence in infectious disease epidemiology, prevention and control that takes different domains and question types into consideration. The methodology rates evidence in four domains: disease burden, risk factors, diagnostics and intervention. The framework guiding it has four steps going from overarching questions to an evidence statement. In step 1, approaches for identifying relevant key areas and developing specific questions to guide systematic evidence searches are described. In step 2, methodological guidance for conducting systematic reviews is provided; 15 study quality appraisal tools are proposed and an algorithm is given for matching a given study design with a tool. In step 3, a standardised evidence-grading scheme using the Grading of Recommendations Assessment, Development and Evaluation Working Group (GRADE) methodology is provided, whereby findings are documented in evidence profiles. Step 4 consists of preparing a narrative evidence summary. Users of this framework should be able to evaluate and grade scientific evidence from the four domains in a transparent and reproducible way.Funding Agencies|European Centre for Disease Prevention and Control (ECDC) [2012/040, 2014/008]</p

Ocular hypertension suppresses homeostatic gene expression in optic nerve head microglia of DBA/2 J mice.

Glaucoma is the leading cause of irreversible vision loss. Ocular hypertension is a major risk factor for glaucoma and recent work has demonstrated critical early neuroinflammatory insults occur in the optic nerve head following ocular hypertension. Microglia and infiltrating monocytes are likely candidates to drive these neuroinflammatory insults. However, the exact molecular identity / transcriptomic profile of microglia following ocular hypertensive insults is unknown. To elucidate the molecular identity of microglia after long-term exposure to ocular hypertension, we used a mouse model of glaucoma (DBA/2 J). We performed RNA-sequencing of microglia mRNA from the optic nerve head at a time point following ocular hypertensive insults, but preceding detectable neurodegeneration (with microglia identified as being CD4