Estrogenic activity, race/ethnicity, and Indigenous American ancestry among San Francisco Bay Area women.

Estrogens play a significant role in breast cancer development and are not only produced endogenously, but are also mimicked by estrogen-like compounds from environmental exposures. We evaluated associations between estrogenic (E) activity, demographic factors and breast cancer risk factors in Non-Latina Black (NLB), Non-Latina White (NLW), and Latina women. We examined the association between E activity and Indigenous American (IA) ancestry in Latina women. Total E activity was measured with a bioassay in plasma samples of 503 women who served as controls in the San Francisco Bay Area Breast Cancer Study. In the univariate model that included all women with race/ethnicity as the independent predictor, Latinas had 13% lower E activity (p = 0.239) and NLBs had 35% higher activity (p = 0.04) compared to NLWs. In the multivariable model that adjusted for demographic factors, Latinas continued to show lower E activity levels (26%, p = 0.026), but the difference between NLBs and NLWs was no longer statistically significant (p = 0.431). An inverse association was observed between E activity and IA ancestry among Latina women (50% lower in 0% vs. 100% European ancestry, p = 0.027) consistent with our previously reported association between IA ancestry and breast cancer risk. These findings suggest that endogenous estrogens and exogenous estrogen-like compounds that act on the estrogen receptor and modulate E activity may partially explain racial/ethnic differences in breast cancer risk

Binding affinities of cucurbit[n]urils with cations

High binding constants of 19 inorganic cations with the cucurbit[n]uril homologues (CBn, n = 5, 6, 7, 8) in water were determined and the far-reaching consequences and interferences of the high affinities (millimolar to micromolar) are discussed

Teaching indicators to unravel the kinetic features of host-guest inclusion complexes

Both thermodynamic and kinetic insights are needed for a proper analysis of association and dissociation processes of host–guest interactions. However, kinetic descriptions of supramolecular systems are scarce in the literature because suitable experimental protocols are lacking. We introduce here three time-resolved methods that allow for convenient determination of kinetic rate constants of spectroscopically silent or even insoluble guests with the macrocyclic cucurbit[n]uril family and human serum albumin (HSA) protein as representative hosts

Cigar Product Modification Among High School Youth

Introduction: Prevalence of cigar use has been increasing among youth. Research indicates that youth are modifying cigar products either by "freaking" (ie, removing the filter paper) or "blunting" (removing the tobacco and supplementing or replacing with marijuana), yet little is known about youth who engage in this behavior. Thus, this study examines demographic and concurrent substance use behaviors of youth who modify cigars. Methods: Data from the 2013 Cuyahoga County Youth Risk Behavior survey were examined (n = 16 855). The survey collected data on demographics, cigar product use, cigar modification behaviors, and current cigarette, hookah and marijuana use. Responses to cigar product use items were used to create a composite to classify youth in one of eight unique user categories. Univariate and bivariate statistics were calculated using SPSS complex samples procedures. Results: Overall, 15.2% reported current cigar product use, 11.0% reported current freaking, and 18.5% reported current blunt use; taken together, 25.3% of respondents reported any current use of a cigar product. When examined by user category, of those who endorsed any cigar product use, cigars, cigarillos, and little cigars use only was most endorsed (26.3%), followed by Blunt only (25.2%) and all three (ie, cigars, cigarillos, and little cigars, freaking, and blunting; 17.4%). Conclusion: A substantial proportion of high school youth who report using cigar products are modifying them in some way, with nearly half freaking and nearly two-thirds blunting. Given the FDA Center for Tobacco products recent extension of its regulatory authority to include cigar products, it is imperative to understand more about the prevalence of and reasons for cigar modification behaviors. Implications: Although the FDA has recently enacted regulatory authority over cigar products, little is known about cigar product modification. This is the first study to concurrently examine two unique cigar modification behaviors, "freaking" (ie, removing the filter paper) and "blunting" (removing the tobacco and supplementing or replacing with marijuana). A significant proportion of high school youth are modifying cigar products to be used as a tobacco product and as a mechanism to smoke marijuana. More research is needed to understand these behaviors to prevent and reduce the use of cigar products among youth

Bacterial genomics reveal the complex epidemiology of an emerging pathogen in Arctic and boreal ungulates

Northern ecosystems are currently experiencing unprecedented ecological change, largely driven by a rapidly changing climate. Pathogen range expansion, and emergence and altered patterns of infectious disease, are increasingly reported in wildlife at high latitudes. Understanding the causes and consequences of shifting pathogen diversity and host-pathogen interactions in these ecosystems is important for wildlife conservation, and for indigenous populations that depend on wildlife. Among the key questions are whether disease events are associated with endemic or recently introduced pathogens, and whether emerging strains are spreading throughout the region. In this study, we used a phylogenomic approach to address these questions of pathogen endemicity and spread for Erysipelothrix rhusiopathiae, an opportunistic multi-host bacterial pathogen associated with recent mortalities in arctic and boreal ungulate populations in North America. We isolated E. rhusiopathiae from carcasses associated with large-scale die-offs of muskoxen in the Canadian Arctic Archipelago, and from contemporaneous mortality events and/or population declines among muskoxen in northwestern Alaska and caribou and moose in western Canada. Bacterial genomic diversity differed markedly among these locations; minimal divergence was present among isolates from muskoxen in the Canadian Arctic, while in caribou and moose populations, strains from highly divergent clades were isolated from the same location, or even from within a single carcass. These results indicate that mortalities among northern ungulates are not associated with a single emerging strain of E. rhusiopathiae, and that alternate hypotheses need to be explored. Our study illustrates the value and limitations of bacterial genomic data for discriminating between ecological hypotheses of disease emergence, and highlights the importance of studying emerging pathogens within the broader context of environmental and host factors

Future perspectives for alkali-activated materials: from existing standards to structural applications

The production of cement and concrete contributes significantly to global greenhouse gas emissions. Alkali-activated concretes (AACs) are a family of existing alternative construction materials that could reduce the current environmental impact of Portland cement (PC) production and utilisation. Successful applications of AACs can be found in Europe and the former USSR since the 1950s and more recently in Australia, China and North America, proving their potential as construction materials. However, their utilisation is limited presently by the lack of normative and construction guidelines. Raw materials’ non-uniform global availability and variable intrinsic properties, coupled with the lack of specific testing methods, raise questions regarding reproducibility and reliability. The mechanical and chemical behaviour of AACs has been investigated extensively over the past decades, strengthening its potential as a sustainable substitute for traditional PC-based concrete. Although a wide amount of studies demonstrated that AACs could meet and even exceed the performance requirements provided by European design standards, a classification of these broad spectra of materials, as well as new analytical models linking the chemistry of the system components to the mechanical behaviour of the material, still need further development. This report gives an overview of the potential of alkali-activated systems technology, focusing on the limitations and challenges still hindering their standardisation and wider application in the construction field

Formation of a TBX20-CASZ1 protein complex is protective against dilated cardiomyopathy and critical for cardiac homeostasis

By the age of 40, one in five adults without symptoms of cardiovascular disease are at risk for developing congestive heart failure. Within this population, dilated cardiomyopathy (DCM) remains one of the leading causes of disease and death, with nearly half of cases genetically determined. Though genetic and high throughput sequencing-based approaches have identified sporadic and inherited mutations in a multitude of genes implicated in cardiomyopathy, how combinations of asymptomatic mutations lead to cardiac failure remains a mystery. Since a number of studies have implicated mutations of the transcription factor TBX20 in congenital heart diseases, we investigated the underlying mechanisms, using an unbiased systems-based screen to identify novel, cardiac-specific binding partners. We demonstrated that TBX20 physically and genetically interacts with the essential transcription factor CASZ1. This interaction is required for survival, as mice heterozygous for both Tbx20 and Casz1 die post-natally as a result of DCM. A Tbx20 mutation associated with human familial DCM sterically interferes with the TBX20-CASZ1 interaction and provides a physical basis for how this human mutation disrupts normal cardiac function. Finally, we employed quantitative proteomic analyses to define the molecular pathways mis-regulated upon disruption of this novel complex. Collectively, our proteomic, biochemical, genetic, and structural studies suggest that the physical interaction between TBX20 and CASZ1 is required for cardiac homeostasis, and further, that reduction or loss of this critical interaction leads to DCM. This work provides strong evidence that DCM can be inherited through a digenic mechanism

The ACS Virgo Cluster Survey. XIV. Analysis of Color-Magnitude Relations in Globular Cluster Systems

We examine the correlation between globular cluster (GC) color and magnitude using HST/ACS imaging for a sample of 79 early-type galaxies (-21.7<M_B<-15.2 mag) with accurate SBF distances from the ACS Virgo Cluster Survey. Using the KMM mixture modeling algorithm, we find a highly significant correlation, d(g-z)/dz = -0.037 +- 0.004, between color and magnitude for the subpopulation of blue GCs in the co-added GC color-magnitude diagram of the three brightest Virgo galaxies (M49, M87 and M60): brighter GCs are redder than their fainter counterparts. For the single GC systems of M87 and M60, we find similar correlations; M49 does not appear to show a significant trend. There is no correlation between (g-z) and M_z for GCs of the red subpopulation. The correlation d(g-z)/dg for the blue subpopulation is much weaker than d(g-z)/dz. Using Monte Carlo simulations, we attribute this to the fact that the blue subpopulation in M_g extends to higher luminosities than the red subpopulation, which biases the KMM fits. The correlation between color and M_z thus is a real effect. This conclusion is supported by biweight fits to the same color distributions. We identify two environmental dependencies of the color-magnitude relation: (1) the slope decreases in significance with decreasing galaxy luminosity; and (2) the slope is stronger for GCs at smaller galactocentric distances. We examine several mechanisms that might give rise to the observed color-magnitude relation: (1) presence of contaminators; (2) accretion of GCs from low-mass galaxies; (3) stochastic effects; (4) capture of field stars by individual GCs; and (5) GC self-enrichment. We conclude that self-enrichment and field-star capture, or a combination of these processes, offer the most promising means of explaining our observations.Comment: 15 pages, 12 figures, accepted for publication in the Astrophysical Journal. Uses emulateapj.cl

Civil conflict, federalism and strategic delegation of leadership

This article analyzes negative externalities that policymakers in one region or group may impose upon the citizens of neighboring regions or groups. These externalities may be material, but they may also be psychological (in the form of envy). The latter form of externality may arise from the production of 'conspicuous' public goods. As a result, decentralized provision of conspicuous public goods may be too high. Potentially, a centralized legislature may internalize negative externalities. However, in a model with strategic delegation, we argue that the median voter in each jurisdiction may anticipate a reduction in local public goods supply and delegate to a policymaker who cares more for public goods than she does herself. This last effect mitigates the expected benefits of policy centralization. The authors' theory is then applied to the setting of civil conflict, where they discuss electoral outcomes in Northern Ireland and Yugoslavia before and after significant institutional changes that affected the degree of centralization. These case studies provide support for the authors' theoretical predictions