Statistical tests for natural selection on regulatory regions based on the strength of transcription factor binding sites

Abstract Background Although cis-regulatory changes play an important role in evolution, it remains difficult to establish the contribution of natural selection to regulatory differences between species. For protein coding regions, powerful tests of natural selection have been developed based on comparisons of synonymous and non-synonymous substitutions, and analogous tests for regulatory regions would be of great utility. Results Here, tests for natural selection on regulatory regions are proposed based on nucleotide substitutions that occur in characterized transcription factor binding sites (an important type functional element within regulatory regions). In the absence of selection, these substitutions will tend to reduce the strength of existing binding sites. On the other hand, purifying selection will act to preserve the binding sites in regulatory regions, while positive selection can act to create or destroy binding sites, as well as change their strength. Using standard models of binding site strength and molecular evolution in the absence of selection, this intuition can be used to develop statistical tests for natural selection. Application of these tests to two well-characterized regulatory regions in Drosophila provides evidence for purifying selection. Conclusion This demonstrates that it is possible to develop tests for selection on regulatory regions based on the specific functional constrains on these sequences

An Evaluation of Standard, Alternative, and Robust Slope Test Strategies

The robustness and power of nine strategies for testing the differences between two groups’ regression slopes under nonnormality and residual variance heterogeneity are compared. The results showed that three most robust slope test strategies were the combination of the trimmed and Winsorized slopes with the James second order test, the combination of Theil-Sen with James, and Theil-Sen with percentile bootstrapping. The slope tests based on Theil-Sen slopes were more powerful than those based on trimmed and Winsorized slopes

The Influence of Data Generation on Simulation Study Results: Tests of Mean Differences

Type I error and power of the standard independent samples t-test were compared with the trimmed and Winsorized t-test with respect to continuous distributions and various discrete distributions known to occur in applied data. The continuous and discrete distributions were generated with similar levels of skew and kurtosis but the discrete distributions had a variety of structural features not reflected in the continuous distributions. The results showed that the Type I error rates of the t-tests were not seriously affected, but the power rate of the trimmed and Winsorized t-test varied greatly across the considered distributions

Testing For Aptitude-Treatment Interactions In Analysis Of Covariance And Randomized Block Designs Under Assumption Violations

This study compared the robustness of two analysis strategies designed to detect Aptitude-Treatment Interactions to two of their similarly-held assumptions, normality and residual variance homogeneity. The analysis strategies were the test of slope differences in analysis of covariance and the test of the Block-by- Treatment interaction in randomized block analysis of variance. With equal sample sizes in the treatment groups the results showed that residual variance heterogeneity has little effect on either strategy but nonnormality makes the test of slope differences liberal and the test of the Block-by-Treatment interaction conservative. With unequal sample sizes in the treatment groups the often-reported sample size-variance heterogeneity pairing is problematic for both strategies. The findings suggest that the randomized block strategy can be characterized as an overly-conservative alternative to the test of slope differences with respect to robustness

Type I Error Rates For Rank-Based Tests Of Homogeneity Of Slopes

The purpose of this study was to explicate two issues concerning the standard and rank based test of homogeneity of slopes. Two alternative ranking methods intended to address nonnormality and additive treatment effect patterns were developed and compared in terms of their ability to control Type I error. The results replicated previous findings of inflated Type I error rates with leptokurtic curves and with rank based tests with some patterns of additive treatment effects. The new nonparametric procedures generally control Type I error although they were slightly inflated with skewed distributions

Bilateral Lower Extremity Ischemia Following Cardiac Catheterization

Acute limb ischemia is a rare yet limb-threatening presentation where rapid diagnosis and intervention is warranted. Bilateral lower extremity ischemia can be a rare complication following procedures, such as a cardiac catheterization with access obtained in the groin. We describe a case of a 79-year-old female who presented with bilateral lower extremity ischemia following a cardiac catheterization 2 weeks prior. The patient underwent CT angiography, which demonstrated occlusion with no contrast present in the bilateral femoral arteries

Working toward a sustainable future

Keyword: Federal policy, international policy, sustainable development, social responsibility, economic conditions, environmental protection, business, industryCitation: Hecht A., Fiksel J., & Moses M. 2014. Working toward a sustainable future. Sustainability: Science, Practice, & Policy 10(2):65-75. Published online Jan 15, 2014. http://sspp.proquest.com/archives/vol10iss2/communityessay.hecht.htmlIntroductionHow can contemporary society address the complex interaction of environmental, social, and economic forces? What factors are currently limiting the sustainability of business enterprises? How can federal and state agencies break down silos and work together to pursue sustainability? What is the preferred model for business-government collaboration and engagement with civil society and nongovernmental organizations (NGOs)? We raise these questions because in the 21st century all sectors of society must confront the challenge of sustaining economic development while protecting critical environmental resources.In 1970, when the modern environmental movement was coalescing and the United States Environmental Protection Agency (USEPA) was created, environmental protection focused mainly on addressing issues related to industrial emissions and occupational health and safety. Most environmental challenges were highly visible and easy for the public to understand. For instance, on June 22, 1969, an oil slick and debris in the Cuyahoga River in Cleveland caught fire, drawing national attention to environmental problems in Ohio and elsewhere in the United States. Time magazine wrote on August 1, 1970, "Some River! Chocolate-brown, oily, bubbling with subsurface gases, it oozes rather than flows."Congress addressed the obvious problems of air, water, and land pollution in the United States through media-specific environmental legislation. In the late 1960s and early 1970s, there was significant bipartisan popular demand for federal leadership in ameliorating pollution problems (Andrews, 2011). The Clean Air Act of 1970, the Clean Water Act of 1972, the Safe Drinking Water Act of 1974, the Resource Conservation and Recovery Act of 1976, and the Comprehensive Environmental Response, Cleanup, and Liability (Superfund) Act of 1980 yielded great progress in improving the quality of the environment. These initiatives relied on federal regulations that set maximum pollutant limits and heavily fined businesses that did not comply. The success of these laws and subsequent regulations is evident today: our air and water are cleaner, less hazardous waste is produced, and contaminated sites are being remediated. Existing regulations provide a strong "safety net" against the domestic impacts of pollution, although the potential remains for environmental problems to be "exported" across global supply chains.Despite these significant accomplishments, newly emerging pressures are threatening the well-being and resilience of human society and the natural environment, thus jeopardizing economic prosperity. The urgency of dealing with today's problems is evident. Worldwide population growth and urban development, as well as globalization of industrial production, have driven increased consumption of energy, water, materials, and land. The consequences include increased greenhouse-gas emissions, decreased biodiversity, and threats to vital natural resources including water bodies, soils, forests, wetlands, and coral reefs. The Millennium Ecosystem Assessment found that fifteen of 24 global ecosystem services are being degraded or exhausted (Hassan et al. 2005). A study by the Stockholm Center for Resilience suggests that on a planetary scale we have exceeded our "safe operating boundaries" in terms of greenhouse-gas emissions, nitrogen flows, and biodiversity (Rockstrom et al. 2009). The Global Footprint Network has estimated that if current trends continue, by the 2030s, we will need the equivalent of two Earths to support the world's population.

Epidemiology and control of intestinal schistosomiasis on the Sesse Islands, Uganda: integrating malacology and parasitology to tailor local treatment recommendations

<p>Abstract</p> <p>Background</p> <p>Intestinal schistosomiasis is often widespread among the populations living around Lake Victoria and on its islands. The Sesse Island group (containing some 84 islands), however, is typically assumed to be a low prevalence zone, with limited transmission, but has never been surveyed in detail. Here, we present a rapid mapping assessment, bringing together snail and parasite information, at 23 sites for the presence of intermediate host snails and at 61 sites for the prevalence of intestinal schistosomiasis in school-aged children (N = 905). Two different diagnostic tools were used and compared at 45 of these sites: Kato-Katz thick faecal smears and circulating cathodic antigen (CCA) urine dipsticks.</p> <p>Results</p> <p><it>Biomphalaria </it>snails were found at 11 sites but in low numbers; none was found shedding schistosome cercariae. At 22 out of the 45 sites, local prevalence by urine and/or stool diagnostics was in excess of 50%, although mean prevalence of intestinal schistosomiasis overall was 34.6% (95% confidence intervals (CI) = 31.0-38.3%) by Kato-Katz and 46.5% (95% CI = 42.7-50.4%) by CCA if 'trace' reactions were considered infection-positive (if considered infection-negative, mean prevalence was 28.1% (95% CI = 24.7-31.7%)). Diagnostic congruence between CCA and Kato-Katz was poor and significant discordance in estimated prevalence by location was found, with each often inferring different mass drug administration regimes.</p> <p>Conclusions</p> <p>Accurate estimation of schistosome prevalence is important for determining present and future treatment needs with praziquantel; the wide range of schistosome prevalence across the Sesse Island group requires a treatment regime largely tailored to each island. In high prevalence locations, further malacological sampling is required to confirm the extent of local transmission, especially on the northern islands within the group. The observation that different diagnostic tests can provide varying results in terms of estimating prevalence by location, and hence change treatment recommendations, suggests that care must be taken in interpreting raw prevalence data. In particular, further research into the reasons for the differences in the poorer performance of the CCA test should be pursued.</p