318 research outputs found

    Effects of Cadmium on Streams and Irrigated Agriculture in the Presence and Absence of Oil Shale Leachate

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    Artificial streams, soil perfusion columns, and potted plants were exposed to 20 ug Cd/l in the presence and absence of unretorted oil shale leachate. High cadmium accumulations occurred in the stream biota, but did not measurably affect community structure or function. The presence of oil shale leachate had no effect on bioaccumulation or ecosystem structure or function. Nitrification in soil columns was enhanced by the presence of the organic fraction of oil shale leachate, but this effect was not observed when cadmium was present. Crop accumulation of cadmium was somewhat higher in alfalfa and radishes irrigated with leachate, but did not cause plant concentrations that would be hazardous to livestock or human consumers

    Successes and Challenges in an Integrated Tuberculosis/HIV Clinic in a Rural, Resource-Limited Setting: Experiences from Kericho, Kenya

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    Objective. To describe TB/HIV clinic outcomes in a rural, Ministry of Health hospital. Design. Retrospective, secondary analyses. Descriptive statistics and logistic regression analyses evaluated baseline characteristics and outcomes. Results. Of 1,911 patients, 89.8% were adults aged 32.0 (±12.6) years with baseline CD4 = 243.3 (±271.0), 18.2% < 50 cells/mm3. Pulmonary (84.8%, (32.2% smear positive)) exceeded extrapulmonary TB (15.2%). Over 5 years, treatment success rose from 40.0% to 74.6%, lost to follow-up dropped from 36.0% to 12.5%, and deaths fell from 20.0% to 5.4%. For patients starting ART after TB treatment, those with CD4 ≥ 50 cells/mm3 were twice as likely to achieve treatment success (OR = 2.0, 95% CI = 1.3–3.1) compared to those with CD4 < 50 cells/mm3. Patients initiating ART at/after 2 months were twice as likely to achieve treatment success (OR = 2.0, 95% CI = 1.3–3.3). Yearly, odds of treatment success improved by 20% (OR = 1.2, 95% CI = 1.0–1.5). Conclusions. An integrated TB/HIV clinic with acceptable outcomes is a feasible goal in resource-limited settings

    Corn Grain, Stover Yield and Nutrient Removal Validations at Regional Partnership Sites

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    Corn (Zea mays L.) stover has been identified as a major feedstock for cellulosic bioenergy. This report summarizes grain and stover yield as well as N, P, and K removal at several Sun Grant Regional Partnership (SGRP) sites. National Agricultural Statistical Service (NASS) grain yields were used to assess the relevancy of plot-scale yields with county averages. Seasonal variation in weather patterns caused yields to differ substantially among sites and years. Nutrient removal estimates were significantly influenced by the sampling method (i.e. analysis of hand samples between physiologic maturity and grain harvest versus stover collected during the harvest operation). Based on ancillary studies that indicate corn stover should not be harvested if average grain yields are less than 175 bu ac-1 (11 Mg ha-1 ), these studies show that non-irrigated SGRP sites with the highest potential for sustainable corn stover harvest were located between -91º and -93º west longitude. The more eastern (-78º w longitude) and western (-96º w longitude) sites did not have sufficient yield for sustainable routine stover harvest, although with good management, corn could still be part of an overall landscape approach for sustainable feedstock production in those areas. For producers with consistently high yields (i.e. \u3e 200 bu ac-1 ) and where residue management may actually be a major problem (e.g. in irrigated areas), moderate stover harvest may actually decrease fuel use and save additional energy by reducing the amount of tillage needed to prepare subsequent seedbeds. Less intensive tillage could also preserve rhizosphere carbon and/or soil structure benefits often attributed to no-till systems

    Three novel mutations in KIF21A highlight the importance of the third coiled-coil stalk domain in the etiology of CFEOM1

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    <p>Abstract</p> <p>Background</p> <p>Congenital fibrosis of the extraocular muscles types 1 and 3 (CFEOM1/CFEOM3) are autosomal dominant strabismus disorders that appear to result from maldevelopment of ocular nuclei and nerves. We previously reported that most individuals with CFEOM1 and rare individuals with CFEOM3 harbor heterozygous mutations in <it>KIF21A</it>. <it>KIF21A </it>encodes a kinesin motor involved in anterograde axonal transport, and the familial and <it>de novo </it>mutations reported to date predictably alter one of only a few KIF21A amino acids – three within the third coiled-coil region of the stalk and one in the distal motor domain, suggesting they result in altered KIF21A function. To further define the spectrum of <it>KIF21A </it>mutations in CFEOM we have now identified all CFEOM probands newly enrolled in our study and determined if they harbor mutations in <it>KIF21A</it>.</p> <p>Results</p> <p>Sixteen CFEOM1 and 29 CFEOM3 probands were studied. Three previously unreported <it>de novo </it>KIF21A mutations were identified in three CFEOM1 probands, all located in the same coiled-coil region of the stalk that contains all but one of the previously reported mutations. Eight additional CFEOM1 probands harbored three of the mutations previously reported in <it>KIF21A</it>; seven had one of the two most common mutations, while one harbored the mutation in the distal motor domain. No mutation was detected in 5 CFEOM1 or any CFEOM3 probands.</p> <p>Conclusion</p> <p>Analysis of sixteen CFEOM1 probands revealed three novel <it>KIF21A </it>mutations and confirmed three reported mutations, bringing the total number of reported <it>KIF21A </it>mutations in CFEOM1 to 11 mutations among 70 mutation positive probands. All three new mutations alter amino acids in heptad repeats within the third coiled-coil region of the KIF21A stalk, further highlighting the importance of alterations in this domain in the etiology of CFEOM1.</p

    VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1

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    Cystic fibrosis (CF) is a fatal genetic disorder associated with defective hydration of lung airways due to the loss of chloride transport through the CF transmembrane conductance regulator protein (CFTR). CFTR contains two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBDs), and a regulatory domain, and its channel assembly requires multiple interdomain contacts. The most common CF-causing mutation, F508del, occurs in NBD1 and results in misfolding and premature degradation of F508del-CFTR. VX-809 is an investigational CFTR corrector that partially restores CFTR function in people who are homozygous for F508del-CFTR. To identify the folding defect(s) in F508del-CFTR that must be repaired to treat CF, we explored the mechanism of VX-809 action. VX-809 stabilized an N-terminal domain in CFTR that contains only MSD1 and efficaciously restored function to CFTR forms that have missense mutations in MSD1. The action of VX-809 on MSD1 appears to suppress folding defects in F508del-CFTR by enhancing interactions among the NBD1, MSD1, and MSD2 domains. The ability of VX-809 to correct F508del-CFTR is enhanced when combined with mutations that improve F508del-NBD1 interaction with MSD2. These data suggest that the use of VX-809 in combination with an additional CFTR corrector that suppresses folding defects downstream of MSD1 may further enhance CFTR function in people with F508del-CFTR

    Marketing Actions and the Value of Customer Assets: A Framework for Customer Asset Management

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    This article develops a framework for assessing how marketing actions affect customers’lifetime value to the firm. The framework is organized around four critical actions that firms must take to effectively manage the asset value of the customer base: database creation, market segmentation, forecasting customer purchase behavior, and resource allocation. In this framework, customer lifetime value is treated as a dynamic construct, that is, it influences the eventual allocation of marketing resources but is also influenced by that allocation. By viewing customers as assets and systematically managing these assets, a firm can identify the most appropriate marketing actions to acquire, maintain, and enhance customer assets and thereby maximize financial returns. The article discusses in detail how to assess customer lifetime value and manage customers as assets. Then, it identifies key research challenges in studying customer asset management and the managerial challenges associated with implementing effective customer asset management practices.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

    Mendelian randomization study of adiposity-related traits and risk of breast, ovarian, prostate, lung and colorectal cancer

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    Background: Adiposity traits have been associated with risk of many cancers in observational studies, but whether these associations are causal is unclear. Mendelian randomization (MR) uses genetic predictors of risk factors as instrumental variables to eliminate reverse causation and reduce confounding bias. We performed MR analyses to assess the possible causal relationship of birthweight, childhood and adult body mass index (BMI), and waist-hip ratio (WHR) on the risks of breast, ovarian, prostate, colorectal and lung cancers. Methods: We tested the association between genetic risk scores and each trait using summary statistics from published genome-wide association studies (GWAS) and from 51 537 cancer cases and 61 600 controls in the Genetic Associations and Mechanisms in Oncology (GAME-ON) Consortium. Results: We found an inverse association between the genetic score for childhood BMI and risk of breast cancer [odds ratio (OR)=0.71 per standard deviation (s.d.) increase in childhood BMI; 95% confidence interval (CI): 0.60, 0.80; P=6.5×10-5). We also found the genetic score for adult BMI to be inversely associated with breast cancer risk (OR=0.66 per s.d. increase in BMI; 95% CI: 0.57, 0.77; P=2.5×10-7), and positively associated with ovarian cancer (OR=1.35; 95% CI: 1.05, 1.72; P=0.017), lung cancer (OR=1.27; 95% CI: 1.09, 1.49; P=2.9×10-3) and colorectal cancer (OR=1.39; 95% CI: 1.06, 1.82, P=0.016). The inverse association between genetically predicted adult BMI and breast cancer risk remained even after adjusting for directional pleiotropy via MR-Egger regression. Conclusions: Findings from this study provide additional understandings of the complex relationship between adiposity and cancer risks. Our results for breast and lung cancer are particularly interesting, given previous reports of effect heterogeneity by menopausal status and smoking status.</p

    Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

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    Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease
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