20 research outputs found

    What Does a Sage-Grouse Eat?

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    Although sage-grouse may eat only sagebrush during the winter, knowing that they need to eat other foods at other times of the year helps wildlife managers implement projects that will ensure a balanced diet. By knowing what a sage-grouse eats and when, we can determine what we need to do to maintain and improve populations and their habitats

    Calculus Volume 2

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    Calculus is designed for the typical two- or three-semester general calculus course, incorporating innovative features to enhance student learning. The book guides students through the core concepts of calculus and helps them understand how those concepts apply to their lives and the world around them. Due to the comprehensive nature of the material, we are offering the book in three volumes for flexibility and efficiency. Volume 2 covers integration, differential equations, sequences and series, and parametric equations and polar coordinates.https://commons.erau.edu/oer-textbook/1001/thumbnail.jp

    Development of a small molecule that corrects misfolding and increases secretion of Z α1 -antitrypsin.

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    Severe α1 -antitrypsin deficiency results from the Z allele (Glu342Lys) that causes the accumulation of homopolymers of mutant α1 -antitrypsin within the endoplasmic reticulum of hepatocytes in association with liver disease. We have used a DNA-encoded chemical library to undertake a high-throughput screen to identify small molecules that bind to, and stabilise Z α1 -antitrypsin. The lead compound blocks Z α1 -antitrypsin polymerisation in vitro, reduces intracellular polymerisation and increases the secretion of Z α1 -antitrypsin threefold in an iPSC model of disease. Crystallographic and biophysical analyses demonstrate that GSK716 and related molecules bind to a cryptic binding pocket, negate the local effects of the Z mutation and stabilise the bound state against progression along the polymerisation pathway. Oral dosing of transgenic mice at 100 mg/kg three times a day for 20 days increased the secretion of Z α1 -antitrypsin into the plasma by sevenfold. There was no observable clearance of hepatic inclusions with respect to controls over the same time period. This study provides proof of principle that "mutation ameliorating" small molecules can block the aberrant polymerisation that underlies Z α1 -antitrypsin deficiency

    Neighborhood Socioeconomic Status and Use of Colonoscopy in an Insured Population – A Retrospective Cohort Study

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    Background: Low-socioeconomic status (SES) is associated with a higher colorectal cancer (CRC) incidence and mortality. Screening with colonoscopy, the most commonly used test in the US, has been shown to reduce the risk of death from CRC. This study examined if, among insured persons receiving care in integrated healthcare delivery systems, differences exist in colonoscopy use according to neighborhood SES. Methods We assembled a retrospective cohort of 100,566 men and women, 50–74 years old, who had been enrolled in one of three US health plans for \geq 1 year on January 1, 2000. Subjects were followed until the date of first colonoscopy, date of disenrollment from the health plan, or December 31, 2007, whichever occurred first. We obtained data on colonoscopy use from administrative records. We defined screening colonoscopy as an examination that was not preceded by gastrointestinal conditions in the prior 6-month period. Neighborhood SES was measured using the percentage of households in each subject's census-tract with an income below 1999 federal poverty levels based on 2000 US census data. Analyses, adjusted for demographics and comorbidity index, were performed using Weibull regression models. Results: The average age of the cohort was 60 years and 52.7% were female. During 449,738 person-years of follow-up, fewer subjects in the lowest SES quartile (Q1) compared to the highest quartile (Q4) had any colonoscopy (26.7% vs. 37.1%) or a screening colonoscopy (7.6% vs. 13.3%). In regression analyses, compared to Q4, subjects in Q1 were 16% (adjusted HR = 0.84, 95% CI: 0.80–0.88) less likely to undergo any colonoscopy and 30%(adjusted HR = 0.70, CI: 0.65–0.75) less likely to undergo a screening colonoscopy. Conclusion: People in lower-SES neighborhoods are less likely to undergo a colonoscopy, even among insured subjects receiving care in integrated healthcare systems. Removing health insurance barriers alone is unlikely to eliminate disparities in colonoscopy use

    Development of a small molecule that corrects misfolding and increases secretion of Z α1‐antitrypsin

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    Abstract Severe α1‐antitrypsin deficiency results from the Z allele (Glu342Lys) that causes the accumulation of homopolymers of mutant α1‐antitrypsin within the endoplasmic reticulum of hepatocytes in association with liver disease. We have used a DNA‐encoded chemical library to undertake a high‐throughput screen to identify small molecules that bind to, and stabilise Z α1‐antitrypsin. The lead compound blocks Z α1‐antitrypsin polymerisation in vitro, reduces intracellular polymerisation and increases the secretion of Z α1‐antitrypsin threefold in an iPSC model of disease. Crystallographic and biophysical analyses demonstrate that GSK716 and related molecules bind to a cryptic binding pocket, negate the local effects of the Z mutation and stabilise the bound state against progression along the polymerisation pathway. Oral dosing of transgenic mice at 100 mg/kg three times a day for 20 days increased the secretion of Z α1‐antitrypsin into the plasma by sevenfold. There was no observable clearance of hepatic inclusions with respect to controls over the same time period. This study provides proof of principle that “mutation ameliorating” small molecules can block the aberrant polymerisation that underlies Z α1‐antitrypsin deficiency

    Patterns in first and daily cigarette initiation among youth and young adults from 2002 to 2015.

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    This study's objective was to describe long-term trends and patterns in first cigarette use (cigarette initiation) and daily cigarette use (daily initiation) among youth and young adults in the U.S. We used cross-sectional survey data from the National Survey on Drug Use and Health, 2002-2015, to estimate annual incidence of first cigarette use (N = 270,556) and first daily cigarette use (N = 373,464) for each year by age groups, race/ethnicity and gender, examining trends over time and the average annual change in initiation for each group. Several clear patterns emerged: 1) cigarette initiation and daily initiation significantly decreased over time among those aged 12-14 and 15-17 and these trends were consistent among nearly all racial/ethnic and gender subgroups; 2) among 18-21 year olds, cigarette initiation sharply increased through 2009, surpassing rates among 15-17 year olds, and sharply declined through 2015 while remaining higher than rates among the younger group, and this trend was consistent for almost all racial/ethnic subgroups; 3) daily initiation for those aged 18-21 significantly declined, and this was significant among most subgroups 4) there was no change in cigarette initiation and daily initiation for 22-25 year olds overall and most subgroups; 5) there was a significant increase in cigarette initiation for 22-25 year old Hispanics males and daily initiation for 22-25 year old males. This study provides a comprehensive look at trends in cigarette and daily initiation among U.S. youth and young adults. Despite notable declines in smoking initiation among youth and young adult populations over the last two decades, targeted prevention and policy efforts are needed for subgroups at higher risk, including young adults and Hispanic males
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