Is the Die Cast? Indian Casino Gambling in Maine

Gambling is the fastest-growing industry in America, earning profits of $45 billion each year. Although gambling on Indian reservations is a$6 billion business, the perception of Indian wealth from gambling revenues is far from reality. Gambling operations provide economic support for only one percent of Indians. Yet, for those who have reaped the high rewards, Indian gambling has become a staple of modern tribal economics. Complex legal issues surround Indian gambling, making it an important and often contentious part of many tribal-state relationships. Maine law prohibits many gambling activities. The Legislature, however, has carved out an exception for federally recognized Indian tribes in Maine, granting them the opportunity to operate high-stakes bingo. Nevertheless, Maine\u27s Passamaquoddy Indian Tribe has fought for the past four years to gain the State\u27s permission to engage in other gambling activities, most notably the construction and operation of a casino in Calais. The Tribe promoted its efforts under the auspices of a 1988 federal law, the Indian Regulatory Gaming Act (IGRA). The IGRA requires states to negotiate with Indian tribes wanting to open and operate gambling enterprises, including casinos. The Maine Legislature failed to pass the numerous bills introduced to authorize application of the IGRA to Maine Indians or to provide a separate statutory basis for a casino. A subsequent decision in the Court of Appeals for the First Circuit denied application of the IGRA to Maine Indians. Faced with both legislative and judicial rejection of its casino plan, the Passamaquoddy Tribe now must reevaluate what the future holds for Indian gaming in Maine. This Comment discusses the policies behind allowing Indians “special” gambling rights, including the doctrine of tribal sovereignty

Do Questions Reflecting Indoor Air Pollutant Exposure from a Questionnaire Predict Direct Measure of Exposure in Owner-Occupied Houses?

Home characteristic questions are used in epidemiological studies and clinical settings to assess potentially harmful exposures in the home. The objective of this study was to determine whether questionnaire-reported home characteristics can predict directly measured pollutants. Sixty home inspections were conducted on a subsample of the 2006 population-based Toronto Child Health Evaluation Questionnaire. Indoor/outdoor air and settled dust samples were analyzed. Mean Fel d 1 was higher (p < 0.0001) in homes with a cat (450.58 μg/g) versus without (22.28 μg/g). Mean indoor NO2 was higher (p = 0.003) in homes with gas stoves (14.98 ppb) versus without (8.31 ppb). Self-reported musty odours predicted higher glucan levels (10554.37 μg/g versus 6308.58 μg/g, p = 0.0077). Der f 1 was predicted by the home’s age, but not by reports of carpets, and was higher in homes with mean relative humidity > 50% (61.30 μg/g, versus 6.24 μg/g, p = 0.002). Self-reported presence of a cat, a gas stove, musty odours, mice, and the home’s age and indoor relative humidity over 50% predicted measured indoor levels of cat allergens, NO2, fungal glucan, mouse allergens and dust mite allergens, respectively. These results are helpful for understanding the significance of indoor exposures ascertained by self-reporting in large epidemiological studies and also in the clinical setting

Expression of Protease-Activated Receptor 1 and 2 and Anti-Tubulogenic Activity of Protease-Activated Receptor 1 in Human Endothelial Colony-Forming Cells

Endothelial colony-forming cells (ECFCs) are obtained from the culture of human peripheral blood mononuclear cell (hPBMNC) fractions and are characterised by high proliferative and pro-vasculogenic potential, which makes them of great interest for cell therapy. Here, we describe the detection of protease-activated receptor (PAR) 1 and 2 amongst the surface proteins expressed in ECFCs. Both receptors are functionally coupled to extracellular signal-regulated kinase (ERK) 1 and 2, which become activated and phosphorylated in response to selective PAR1- or PAR2-activating peptides. Specific stimulation of PAR1, but not PAR2, significantly inhibits capillary-like tube formation by ECFCs in vitro, suggesting that tubulogenesis is negatively regulated by proteases able to stimulate PAR1 (e.g. thrombin). The activation of ERKs is not involved in the regulation of tubulogenesis in vitro, as suggested by use of the MEK inhibitor PD98059 and by the fact that PAR2 stimulation activates ERKs without affecting capillary tube formation. Both qPCR and immunoblotting showed a significant downregulation of vascular endothelial growth factor 2 (VEGFR2) in response to PAR1 stimulation. Moreover, the addition of VEGF (50–100 ng/ml) but not basic Fibroblast Growth Factor (FGF) (25–100 ng/ml) rescued tube formation by ECFCs treated with PAR1-activating peptide. Therefore, we propose that reduction of VEGF responsiveness resulting from down-regulation of VEGFR2 is underlying the anti-tubulogenic effect of PAR1 activation. Although the role of PAR2 remains elusive, this study sheds new light on the regulation of the vasculogenic activity of ECFCs and suggests a potential link between adult vasculogenesis and the coagulation cascade

Conceptualising examinable physical education in the Irish context: Leaving Certificate Physical Education

peer-reviewedA Physical Education Development Group (PEDG) was responsible for constructing a new school subject curriculum, Leaving Certificate Physical Education (LCPE), in Ireland. This paper provides an insight into this development group and explores the process of curriculum development, and the influence of roles and power-ratios within the group, in the construction of the LCPE curriculum. Figurational sociology concepts (Elias, 1978) were drawn on to make sense of the curriculum makers’ experiences. Interviews were conducted with 10 PEDG members. The findings suggest that the members’ roles had very little, if any, influence on the curriculum development process. Findings also revolved around the unbalanced power-ratios which existed in the PEDG and highlighted the socially powerful position of ‘strong, well-established’ (in the academic field of curriculum development – participant's words) members and the other members (predominantly representing practicing teachers). We express concern for the role of teachers in the curriculum process and argue that they play a crucial and significant role in the school subject curriculum development process. This paper supports Goodson’s (1983) and Penney’s (2006) conceptualisation of the contested and socially constructed nature of the curriculum development process.peer-reviewe

Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design.

Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)-many of which are refractory to current standard-of-care treatments-from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer

Phase IIb, Randomized, Double-Blind Trial of GC4419 Versus Placebo to Reduce Severe Oral Mucositis Due to Concurrent Radiotherapy and Cisplatin For Head and Neck Cancer

PURPOSE: Oral mucositis (OM) remains a common, debilitating toxicity of radiation therapy (RT) for head and neck cancer. The goal of this phase IIb, multi-institutional, randomized, double-blind trial was to compare the efficacy and safety of GC4419, a superoxide dismutase mimetic, with placebo to reduce the duration, incidence, and severity of severe OM (SOM). PATIENTS AND METHODS: A total of 223 patients (from 44 institutions) with locally advanced oral cavity or oropharynx cancer planned to be treated with definitive or postoperative intensity-modulated RT (IMRT; 60 to 72 Gy [≥ 50 Gy to two or more oral sites]) plus cisplatin (weekly or every 3 weeks) were randomly assigned to receive 30 mg (n = 73) or 90 mg (n = 76) of GC4419 or to receive placebo (n = 74) by 60-minute intravenous administration before each IMRT fraction. WHO grade of OM was assessed biweekly during IMRT and then weekly for up to 8 weeks after IMRT. The primary endpoint was duration of SOM tested for each active dose level versus placebo (intent-to-treat population, two-sided α of .05). The National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03, was used for adverse event grading. RESULTS: Baseline patient and tumor characteristics as well as treatment delivery were balanced. With 90 mg GC4419 versus placebo, SOM duration was significantly reduced (P = .024; median, 1.5 v 19 days). SOM incidence (43% v 65%; P = .009) and severity (grade 4 incidence, 16% v 30%; P = .045) also were improved. Intermediate improvements were seen with the 30-mg dose. Safety was comparable across arms, with no significant GC4419-specific toxicity nor increase of known toxicities of IMRT plus cisplatin. The 2-year follow-up for tumor outcomes is ongoing. CONCLUSION: GC4419 at a dose of 90 mg produced a significant, clinically meaningful reduction of SOM duration, incidence, and severity with acceptable safety

Continental-scale homogenization of residential lawn plant communities

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Landscape and Urban Planning 165 (2017): 54-63, doi:10.1016/j.landurbplan.2017.05.004.Residential lawns are highly managed ecosystems that occur in urbanized landscapes across the United States. Because they are ubiquitous, lawns are good systems in which to study the potential homogenizing effects of urban land use and management together with the continental-scale effects of climate on ecosystem structure and functioning. We hypothesized that similar homeowner preferences and management in residential areas across the United States would lead to low plant species diversity in lawns and relatively homogeneous vegetation across broad geographical regions. We also hypothesized that lawn plant species richness would increase with regional temperature and precipitation due to the presence of spontaneous, weedy vegetation, but would decrease with household income and fertilizer use. To test these predictions, we compared plant species composition and richness in residential lawns in seven U.S. metropolitan regions. We also compared species composition in lawns with understory vegetation in minimally-managed reference areas in each city. As expected, the composition of cultivated turfgrasses was more similar among lawns than among reference areas, but this pattern also held among spontaneous species. Plant species richness and diversity varied more among lawns than among reference areas, and more diverse lawns occurred in metropolitan areas with higher precipitation. Native forb diversity increased with precipitation and decreased with income, driving overall lawn diversity trends with these predictors as well. Our results showed that both management and regional climate shaped lawn species composition, but the overall homogeneity of species regardless of regional context strongly suggested that management was a more important driver.This research was supported by the Macrosystems Biology Program in the Emerging Frontiers Division of the Biological Sciences Directorate at the National Science Foundation (NSF) under grants EF-1065548, 1065737, 1065740, 1065741, 1065772, 1065785, 1065831, and 121238320

A systems approach for discovering linoleic acid derivatives that potentially mediate pain and itch

Chronic pain and itch are common hypersensitivity syndromes that are affected by endogenous mediators. We applied a systems-based, translational approach to predict, discover, and characterize mediators of pain and itch that are regulated by diet and inflammation. Profiling of tissue-specific precursor abundance and biosynthetic gene expression predicted that inflamed skin would be abundant in four previously unknown 11-hydroxy-epoxy- or 11-keto-epoxy-octadecenoate linoleic acid derivatives and four previously identified 9- or 13-hydroxy-epoxy- or 9- or 13-keto-epoxy-octadecenoate linoleic acid derivatives. All of these mediators were confirmed to be abundant in rat and human skin by mass spectrometry. However, only the two 11-hydroxy-epoxy-octadecenoates sensitized rat dorsal root ganglion neurons to release more calcitonin gene-related peptide (CGRP), which is involved in pain transmission, in response to low pH (which mimics an inflammatory state) or capsaicin (which activates ion channels involved in nociception). The two 11-hydroxy-epoxy-octadecenoates share a 3-hydroxy-Z-pentenyl-E-epoxide moiety, thus suggesting that this substructure could mediate nociceptor sensitization. In rats, intradermal hind paw injection of 11-hydroxy-12,13-trans-epoxy-(9Z)-octadecenoate elicited C-fiber-mediated sensitivity to thermal pain. In a randomized trial testing adjunctive strategies to manage refractory chronic headaches, reducing the dietary intake of linoleic acid was associated with decreases in plasma 11-hydroxy-12,13-trans-epoxy-(9Z)-octadecenoate, which correlated with clinical pain reduction. Human psoriatic skin had 30-fold higher 9-keto-12,13-trans-epoxy-(10E)-octadecenoate compared to control skin, and intradermal injection of this compound induced itch-related scratching behavior in mice. Collectively, these findings define a family of endogenous mediators with potential roles in pain and itch

Analysis of HIV Diversity in HIV-Infected Black Men Who Have Sex with Men (HPTN 061)

Background: HIV populations often diversify in response to selective pressures, such as the immune response and antiretroviral drug use. We analyzed HIV diversity in Black men who have sex with men who were enrolled in the HIV Prevention Trials Network 061 study. Methods: A high resolution melting (HRM) diversity assay was used to measure diversity in six regions of the HIV genome: two in gag, one in pol, and three in env. HIV diversity was analyzed for 146 men who were HIV infected at study enrollment, including three with acute infection and 13 with recent infection (identified using a multi-assay algorithm), and for 21 men who seroconverted during the study. HIV diversification was analyzed in a paired analysis for 62 HIV-infected men using plasma samples from the enrollment and 12-month (end of study) visits. Results: Men with acute or recent infection at enrollment and seroconverters had lower median HRM scores (lower HIV diversity) than men with non-recent infection in all six regions analyzed. In univariate analyses, younger age, higher CD4 cell count, and HIV drug resistance were associated with lower median HRM scores in multiple regions; ARV drug detection was marginally associated with lower diversity in the pol region. In multivariate analysis, acute or recent infection (all six regions) and HIV drug resistance (both gag regions) were associated with lower median HRM scores. Diversification in the pol region over 12 months was greater for men with acute or recent infection, higher CD4 cell count, and lower HIV viral load at study enrollment. Conclusions: HIV diversity was significantly associated with duration of HIV infection, and lower gag diversity was observed in men who had HIV drug resistance. HIV pol diversification was more pronounced in men with acute or recent infection, higher CD4 cell count, and lower HIV viral load

Climate and lawn management interact to control C4 plant distribution in residential lawns across seven U.S. cities.

Author Posting. © Ecological Society of America, 2019. This article is posted here by permission of Ecological Society of America for personal use, not for redistribution. The definitive version was published in Trammell, T. L. E., Pataki, D. E., Still, C. J., Ehleringer, J. R., Avolio, M. L., Bettez, N., Cavender-Bares, J., Groffman, P. M., Grove, M., Hall, S. J., Heffernan, J., Hobbie, S. E., Larson, K. L., Morse, J. L., Neill, C., Nelson, K. C., O'Neil-Dunne, J., Pearse, W. D., Chowdhury, R. R., Steele, M., & Wheeler, M. M. Climate and lawn management interact to control C4 plant distribution in residential lawns across seven U.S. cities. Ecological Applications, 29(4), (2019): e01884, doi: 10.1002/eap.1884.In natural grasslands, C4 plant dominance increases with growing season temperatures and reflects distinct differences in plant growth rates and water use efficiencies of C3 vs. C4 photosynthetic pathways. However, in lawns, management decisions influence interactions between planted turfgrass and weed species, leading to some uncertainty about the degree of human vs. climatic controls on lawn species distributions. We measured herbaceous plant carbon isotope ratios (δ13C, index of C3/C4 relative abundance) and C4 cover in residential lawns across seven U.S. cities to determine how climate, lawn plant management, or interactions between climate and plant management influenced C4 lawn cover. We also calculated theoretical C4 carbon gain predicted by a plant physiological model as an index of expected C4 cover due to growing season climatic conditions in each city. Contrary to theoretical predictions, plant δ13C and C4 cover in urban lawns were more strongly related to mean annual temperature than to growing season temperature. Wintertime temperatures influenced the distribution of C4 lawn turf plants, contrary to natural ecosystems where growing season temperatures primarily drive C4 distributions. C4 cover in lawns was greatest in the three warmest cities, due to an interaction between climate and homeowner plant management (e.g., planting C4 turf species) in these cities. The proportion of C4 lawn species was similar to the proportion of C4 species in the regional grass flora. However, the majority of C4 species were nonnative turf grasses, and not of regional origin. While temperature was a strong control on lawn species composition across the United States, cities differed as to whether these patterns were driven by cultivated lawn grasses vs. weedy species. In some cities, biotic interactions with weedy plants appeared to dominate, while in other cities, C4 plants were predominantly imported and cultivated. Elevated CO2 and temperature in cities can influence C3/C4 competitive outcomes; however, this study provides evidence that climate and plant management dynamics influence biogeography and ecology of C3/C4 plants in lawns. Their differing water and nutrient use efficiency may have substantial impacts on carbon, water, energy, and nutrient budgets across cities.This research was funded by a series of collaborative grants from the U.S. National Science Foundation Macrosystems Biology Program (EF‐1065548, 1065737, 1065740, 1065741, 1065772, 1065785, 1065831, 121238320). The authors thank La'Shaye Ervin, William Borrowman, Moumita Kundu, and Barbara Uhl for field and laboratory assistance