235 research outputs found

    Finding the Fit Between Housing Strategies and Housing Consumers

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    The housing crisis stripped many families of their wealth, especially those in communities of color. This presentation will examine when and for whom homeownership is the right wealth building strategy

    Structural Inequality and the New Markets Tax Credit

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    The New Markets Tax Credit (“NMTC”) is a federal tax incentive used to promote investment in low-income neighborhoods. Many of these neighborhoods are home to historically marginalized communities. However, very few minority-led institutions participate in the NMTC program. This Article provides the first theoretical and empirical exploration of the underrepresentation of minority-led institutions in the NMTC program. Based on original interviews with representatives of Community Development Entities (“CDEs”), investors, borrowers, and consultants who participate in the NMTC program, this Article describes the “NMTC ecosystem,” a complex, relationship-driven network of NMTC program participants who influence decision-making and create opportunities for success within the NMTC program. The Article demonstrates that within the NMTC ecosystem, minority-led CDEs face structural barriers to entry similar to those that exist in purely private markets, such as unequal access to professional networks and lack of track records. Troublingly, those barriers are intensifying with time. The underrepresentation of minority-led CDEs in the NMTC program undermines its capacity to promote equitable economic development. To remedy that problem, this Article proposes that the Treasury should increase transparency and guidance in its administrative process, engage institutional intermediaries to aid minority-led CDEs, and relax requirements that chill participation among minority-led CDEs. These insights and prescriptions have relevance well beyond the context of the NMTC. In many domains, regulators have adopted measures that aim to promote equitable community development. This Article’s findings and reform recommendations thus have important implications for the broader universe of place-based regulatory policies, including for the many other tax incentive programs that aim to promote equity and reduce economic marginalization

    Is a clean river fun for all? Recognizing social vulnerability in watershed planning

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    Watershed planning can lead to policy innovation and action toward environmental protection. However, groups often suffer from low engagement with communities that experience disparate impacts from flooding and water pollution. This can limit the capacity of watershed efforts to dismantle pernicious forms of social inequality. As a result, the benefits of environmental changes often flow to more empowered residents, short-changing the power of watershed-based planning as a tool to transform ecological, economic, and social relationships. The objectives of this paper are to assess whether the worldview of watershed planning actors are sufficiently attuned to local patterns of social vulnerability and whether locally significant patterns of social vulnerability can be adequately differentiated using conventional data sources. Drawing from 35 in-depth interviews with watershed planners and community stakeholders in the Milwaukee River Basin (WI, USA), we identify five unique definitions of social vulnerability. Watershed planners in our sample articulate a narrower range of social vulnerability definitions than other participants. All five definitions emphasize spatial and demographic characteristics consistent with existing ways of measuring social vulnerability. However, existing measures do not adequately differentiate among the spatio-temporal dynamics used to distinguish definitions. In response, we develop two new social vulnerability measures. The combination of interviews and demographic analyses in this study provides an assessment technique that can help watershed planners (a) understand the limits of their own conceptualization of social vulnerability and (b) acknowledge the importance of place-based vulnerabilities that may otherwise be obscured. We conclude by discussing how our methods can be a useful tool for identifying opportunities to disrupt social vulnerability in a watershed by evaluating how issue frames, outreach messages, and engagement tactics. The approach allows watershed planners to shift their own culture in order to consider socially vulnerable populations comprehensively.Illinois-Indiana Sea Grant NA14OAR4170095Ope

    Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma

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    BACKGROUND: We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA) directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints. METHODS: From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse < 6 months after first course of chemotherapy). There was evidence of cisplatin resistance in 31 patients from their first ATP-TCA. Response to treatment was assessed by radiology, clinical assessment and tumor marker level (CA 125). RESULTS: The overall response rate was 59% (33/56) per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS) was 6.6 months per course of chemotherapy; median overall survival (OAS) for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9-12.8 months). CONCLUSION: The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centre

    Cathepsin K in lymphangioleiomyomatosis: LAM cell-fibroblast Interactions enhance protease activity by extracellular acidification

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    Lymphangioleiomyomatosis (LAM) is a rare disease in which clonal ‘LAM’ cells infiltrate the lungs and lymphatics. In association with recruited fibroblasts, LAM cells form nodules adjacent to lung cysts. It is assumed LAM nodule derived proteases lead to cyst formation although, this is uncertain. We profiled protease gene expression in whole lung tissue and observed cathepsin K was 40 fold over-expressed in LAM compared with control lungs (p≤0.0001). Immunohistochemistry confirmed cathepsin K protein in LAM nodules but not control lungs. Cathepsin K gene expression, protein and protease activity was detected in LAM associated fibroblasts but not the LAM cell line 621-101. In lung nodules, cathepsin K immune reactivity was predominantly co-localised with LAM associated fibroblasts. In vitro, extra-cellular cathepsin K activity was minimal at pH 7.5 but significantly enhanced in fibroblast cultures at pH 7 and 6. 621-101 cells reduced extracellular pH by 0.5 units over 24 hours. Acidification was dependent upon 621-101 cell mTOR activity and net hydrogen ion transporters, particularly sodium/bicarbonate co-transporters and carbonic anhydrases which were also expressed in LAM lung tissue. In LAM cell/fibroblast co-cultures, acidification paralleled cathepsin K activity and both were inhibited by sodium bicarbonate co-transporter (p≤0.0001) and carbonic anhydrase inhibitors (p=0.0021). Our findings suggest cathepsin K activity is dependent on LAM cell/fibroblast interactions and inhibitors of extracellular acidification may be potential therapies for LAM

    The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

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    The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

    The Herbicide Atrazine Activates Endocrine Gene Networks via Non-Steroidal NR5A Nuclear Receptors in Fish and Mammalian Cells

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    Atrazine (ATR) remains a widely used broadleaf herbicide in the United States despite the fact that this s-chlorotriazine has been linked to reproductive abnormalities in fish and amphibians. Here, using zebrafish we report that environmentally relevant ATR concentrations elevated zcyp19a1 expression encoding aromatase (2.2 µg/L), and increased the ratio of female to male fish (22 µg/L). ATR selectively increased zcyp19a1, a known gene target of the nuclear receptor SF-1 (NR5A1), whereas zcyp19a2, which is estrogen responsive, remained unchanged. Remarkably, in mammalian cells ATR functions in a cell-specific manner to upregulate SF-1 targets and other genes critical for steroid synthesis and reproduction, including Cyp19A1, StAR, Cyp11A1, hCG, FSTL3, LHß, INHα, αGSU, and 11ß-HSD2. Our data appear to eliminate the possibility that ATR directly affects SF-1 DNA- or ligand-binding. Instead, we suggest that the stimulatory effects of ATR on the NR5A receptor subfamily (SF-1, LRH-1, and zff1d) are likely mediated by receptor phosphorylation, amplification of cAMP and PI3K signaling, and possibly an increase in the cAMP-responsive cellular kinase SGK-1, which is known to be upregulated in infertile women. Taken together, we propose that this pervasive and persistent environmental chemical alters hormone networks via convergence of NR5A activity and cAMP signaling, to potentially disrupt normal endocrine development and function in lower and higher vertebrates

    Induction of the interleukin 6/ signal transducer and activator of transcription pathway in the lungs of mice sub-chronically exposed to mainstream tobacco smoke

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    <p>Abstract</p> <p>Background</p> <p>Tobacco smoking is associated with lung cancer and other respiratory diseases. However, little is known about the global molecular changes that precede the appearance of clinically detectable symptoms. In this study, the effects of mainstream tobacco smoke (MTS) on global transcription in the mouse lung were investigated.</p> <p>Methods</p> <p>Male C57B1/CBA mice were exposed to MTS from two cigarettes daily, 5 days/week for 6 or 12 weeks. Mice were sacrificed immediately, or 6 weeks following the last cigarette. High density DNA microarrays were used to characterize global gene expression changes in whole lung. Microarray results were validated by Quantitative real-time RT-PCR. Further analysis of protein synthesis and function was carried out for a select set of genes by ELISA and Western blotting.</p> <p>Results</p> <p>Globally, seventy nine genes were significantly differentially expressed following the exposure to MTS. These genes were associated with a number of biological processes including xenobiotic metabolism, redox balance, oxidative stress and inflammation. There was no differential gene expression in mice exposed to smoke and sampled 6 weeks following the last cigarette. Moreover, cluster analysis demonstrated that these samples clustered alongside their respective controls. We observed simultaneous up-regulation of <it>interleukin 6 </it>(<it>IL-6</it>) and its antagonist, <it>suppressor of cytokine signalling </it>(<it>SOCS3</it>) mRNA following 12 weeks of MTS exposure. Analysis by ELISA and Western blotting revealed a concomitant increase in total IL-6 antigen levels and its downstream targets, including phosphorylated signal transducer and activator of transcription 3 (Stat3), basal cell-lymphoma extra large (BCL-XL) and myeloid cell leukemia 1 (MCL-1) protein, in total lung tissue extracts. However, in contrast to gene expression, a subtle decrease in total SOCS3 protein was observed after 12 weeks of MTS exposure.</p> <p>Conclusion</p> <p>Global transcriptional analysis identified a set of genes responding to MTS exposure in mouse lung. These genes returned to basal levels following smoking cessation, providing evidence to support the benefits of smoking cessation. Detailed analyses were undertaken for IL-6 and its associated pathways. Our results provide further insight into the role of these pathways in lung injury and inflammation induced by MTS.</p

    Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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    Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries
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