Local Residents\u27 Experience of the Coal Ash Spill in Kingston, Tennessee: A Phenomenological Study

On December 22, 2008, near Kingston, Tennessee, a Tennessee Valley Authority (TVA) retention pond holding approximately 1.7 million cubic yards of coal fly ash failed, spilling the ash into the nearby Emory River and inundating farms and homes in the Swan Pond community. As a result more than 100 people were permanently displaced from their homes and the clean-up effort is ongoing. The purpose of this study was to explore the experience of living near Kingston, Tennessee, in the aftermath of the spill. Using existential phenomenology as the guiding research methodology, I interviewed 9 participants from the area and asked the question, “Please tell me about a time when you have been aware of the ash spill.” Interviews were digitally recorded, transcribed, and analyzed using an approach to existential phenomenological research developed by Thomas and Pollio (2002). Analysis of the interview transcripts revealed four themes: 1) Change, Loss, and Uncertainty, 2) Inconvenience, 3) Powerlessness in the Face of Government (“You can’t fight city hall”), and 4) Shouldering the Cost Burden/People Getting Something for Nothing (in general, economics). In addition, three sub-themes were identified with Change, Loss, and Uncertainty: landscape, community, and recreation. Each theme stood out against the dual grounds of the world and time. A review of the literature in conjunction with the theme analysis indicates two theories at work: inhibition of collective action and a generational power structure that contributes to quiescence

PPARγ is a Major Driver of the Accumulation and Phenotype of Adipose-Tissue TregT_{reg} Cells

Obesity and type-2 diabetes have increased markedly over the past few decades, in parallel. One of the major links between these two disorders is chronic, low-grade inflammation. Prolonged nutrient excess promotes the accumulation and activation of leukocytes in visceral adipose tissue (VAT) and ultimately other tissues, leading to metabolic abnormalities such as insulin resistance, type-2 diabetes and fatty-liver disease. Although invasion of VAT by pro-inflammatory macrophages is considered to be a key event driving adipose-tissue inflammation and insulin resistance, little is known about the roles of other immune system cell types in these processes. A unique population of VAT-resident regulatory T $(T_{reg})$ cells was recently implicated in control of the inflammatory state of adipose tissue and, thereby, insulin sensitivity. Here we identify peroxisome proliferator-activated receptor (PPAR)-γ, the ‘master regulator’ of adipocyte differentiation, as a crucial molecular orchestrator of VAT $T_{reg}$ cell accumulation, phenotype and function. Unexpectedly, PPAR-γ expression by VAT $T_{reg}$ cells was necessary for complete restoration of insulin sensitivity in obese mice by the thiazolidinedione drug pioglitazone. These findings suggest a previously unknown cellular mechanism for this important class of thiazolidinedione drugs, and provide proof-of-principle that discrete populations of $T_{reg}$ cells with unique functions can be precisely targeted to therapeutic ends

Circulating C3 is Necessary and Sufficient for Induction of Autoantibody-Mediated Arthritis in a Mouse Model

Objective. For the inflammation characteristic of rheumatoid arthritis, the relative contribution of mediators produced locally in the synovium versus those circulating systemically is unknown. Complement factor C3 is made in rheumatoid synovium and has been proposed to be a crucial driver of inflammation. The aim of this study was to test, in a mouse model of rheumatoid arthritis, whether C3 synthesized within the synovium is important in promoting inflammation. Methods. Radiation bone marrow chimeras between normal and C3−/− mice were constructed in order to generate animals that expressed or lacked expression of C3 only in hematopoietic cells. Parabiotic mice were made by surgically linking C3−/− mice to irradiated wild-type mice to obtain animals having C3 only in the circulation. Arthritis was induced by injection of serum from arthritic K/BxN mice.Results In bone marrow chimeras, synthesis of C3 by radioresistant cells was necessary and sufficient to confer susceptibility to serum-transferred arthritis. Parabionts having C3 only in the circulation remained sensitive to arthritis induction, and the cartilage of these arthritic mice contained deposits of C3. Conclusion. In a mouse model in which the alternative pathway of complement activation is critical to the induction of arthritis by autoantibodies, circulating C3 was necessary and sufficient for arthritis induction.Stem Cell and Regenerative Biolog

Effects of Thresholding on Voxel-Wise Correspondence of Breath-Hold and Resting-State Maps of Cerebrovascular Reactivity

Functional magnetic resonance imaging for presurgical brain mapping enables neurosurgeons to identify viable tissue near a site of operable pathology which might be at risk of surgery-induced damage. However, focal brain pathology (e.g., tumors) may selectively disrupt neurovascular coupling while leaving the underlying neurons functionally intact. Such neurovascular uncoupling can result in false negatives on brain activation maps thereby compromising their use for surgical planning. One way to detect potential neurovascular uncoupling is to map cerebrovascular reactivity using either an active breath-hold challenge or a passive resting-state scan. The equivalence of these two methods has yet to be fully established, especially at a voxel level of resolution. To quantitatively compare breath-hold and resting-state maps of cerebrovascular reactivity, we first identified threshold settings that optimized coverage of gray matter while minimizing false responses in white matter. When so optimized, the resting-state metric had moderately better gray matter coverage and specificity. We then assessed the spatial correspondence between the two metrics within cortical gray matter, again, across a wide range of thresholds. Optimal spatial correspondence was strongly dependent on threshold settings which if improperly set tended to produce statistically biased maps. When optimized, the two CVR maps did have moderately good correspondence with each other (mean accuracy of 73.6%). Our results show that while the breath-hold and resting-state maps may appear qualitatively similar they are not quantitatively identical at a voxel level of resolution