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UNC-authored articles published by the Public Library of Science (PLoS)

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1901. Assessing infection control practices to protect health care workers and patients in Malawi from nosocomial transmission of Mycobacterium tuberculosis

Title Tesim:
Assessing infection control practices to protect health care workers and patients in Malawi from nosocomial transmission of Mycobacterium tuberculosis
Creator:
Munthali, Adamson, Kazembe, Peter N., Kim, Maria H., Simon, Katherine, Mlauzi, Lameck, Flick, Robert J., Ahmed, Saeed, and Hosseinipour, Mina
Date of publication:
2017
Abstract Tesim:
Transmission of Mycobacterium tuberculosis (TB) in health settings threatens health care workers and people living with HIV in sub-Saharan Africa. Nosocomial transmission is reduced with implementation of infection control (IC) guidelines. The objective of this study is to describe implementation of TB IC measures in Malawi. We conducted a cross-sectional study utilizing anonymous health worker questionnaires, semi-structured interviews with facility managers, and direct observations at 17 facilities in central Malawi. Of 592 health care workers surveyed, 34% reported that all patients entering the facility were screened for cough and only 8% correctly named the four most common signs and symptoms of TB in adults. Of 33 managers interviewed, 7 (21%) and 1 (3%) provided the correct TB screening questions for use in adults and children, respectively. Of 592 health workers, only 2.4% had been screened for TB in the previous year. Most (90%) reported knowing their HIV status, 53% were tested at their facility of employment, and half reported they would feel comfortable receiving ART or TB treatment at their facility of employment. We conclude that screening is infrequently conducted and knowledge gaps may undercut its effectiveness. Further, health care workers do not routinely access TB and HIV diagnostic and treatment services at their facility of employment.
Resource type:
Article
Affiliation Label Tesim:
UNC Project-Malawi
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/vqe5-bd55
Identifier:
Onescience id: f1aada3da18ef485a837d4f870c229cc193e837e, Publisher DOI: https://doi.org/10.1371/journal.pone.0189140, PMCID: PMC5718482, and PMID: 29211793
ISSN:
1932-6203
Journal Issue:
12
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Health screening, Tuberculosis, HIV, Coughing, Malawi, Mycobacterium tuberculosis, Patients, and Antiretroviral therapy
Language Label:
English
ORCID:
Other Affiliation:
Baylor College of Medicine Children’s Foundation Malawi, Baylor International Pediatric AIDS Initiative at Texas Children’s Hospital; Baylor College of Medicine, Malawi Ministry of Health National Tuberculosis Control Programme, University of Colorado School of Medicine, and University of North Carolina at Chapel Hill
Page Start:
e0189140
Person:
Munthali, Adamson, Kazembe, Peter N., Kim, Maria H., Simon, Katherine, Mlauzi, Lameck, Flick, Robert J., Ahmed, Saeed, and Hosseinipour, Mina
Rights Statement Label:
In Copyright
Source:
xk81jr524

1902. Area-level poverty, race/ethnicity & dialysis star ratings

Title Tesim:
Area-level poverty, race/ethnicity & dialysis star ratings
Creator:
Flythe, Jennifer E., Chin, Andrew I., Manickam, Raj N., Mu, Yi, Bang, Heejung, and Kshirsagar, Abhijit V.
Date of publication:
2017
Abstract Tesim:
The Centers for Medicare and Medicaid Services recently released a five star rating system as part of ‘Dialysis Facility Compare’ to help patients identify and choose high performing clinics in the US. Eight dialysis-related measures determine ratings. Little is known about the association between surrounding community sociodemographic characteristics and star ratings. Using data from the U.S. Census and over 6000 dialysis clinics across the country, we examined the association between dialysis clinic star ratings and characteristics of the local population: 1) proportion of population below the federal poverty level (FPL); 2) proportion of black individuals; and 3) proportion of Hispanic individuals, by correlation and regression analyses. Secondary analyses with Quality Incentive Program (QIP) scores and population characteristics were also performed. We observed a negligible correlation between star ratings and the proportion of local individuals below FPL; Spearman coefficient, R = -0.09 (p<0.0001), and a stronger correlation between star ratings and the proportion of black individuals; R = -0.21 (p<0.0001). Ordered logistic regression analyses yielded adjusted odds ratio of 0.91 (95% confidence interval [0.80–1.30], p = 0.12) and 0.55 ([0.48–0.63], p<0.0001) for high vs. low level of proportion below FPL and proportion of black individuals, respectively. In contrast, a near-zero correlation was observed between star ratings and the proportion of Hispanic individuals. Correlations varied substantially by country region, clinic profit status and clinic size. Analyses using clinic QIP scores provided similar results. Sociodemographic characteristics of the surrounding community, factors typically outside of providers’ direct control, have varying levels of association with clinic dialysis star ratings.
Resource type:
Article
Affiliation Label Tesim:
School of Medicine
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/rsq4-pf72
Identifier:
Onescience id: 921d118300602bfa4e72b61c4149c8a47d07476b, PMID: 29040342, Publisher DOI: https://doi.org/10.1371/journal.pone.0186651, and PMCID: PMC5645143
ISSN:
1932-6203
Journal Issue:
10
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Medicaid, Medicare, Hispanic Americans, Poverty Areas, Odds Ratio, Ambulatory Care Facilities, Humans, Renal Dialysis, Logistic Models, Centers for Medicare and Medicaid Services (U.S.), Quality Indicators, Health Care, United States, and African Americans
Language Label:
English
ORCID:
Other Affiliation:
Division of Nephrology; University of California; Davis School of Medicine, Division of Nephrology; Sacramento VA Medical Center; VA Northern California Health Care Systems; Mather Field, Graduate Group in Epidemiology; University of California; Davis, Center for Healthcare Policy and Research; School of Medicine; University of California; Sacramento, and Division of Biostatistics; Department of Public Health Sciences; University of California; Davis
Page Start:
e0186651
Person:
Flythe, Jennifer E., Chin, Andrew I., Manickam, Raj N., Mu, Yi, Bang, Heejung, and Kshirsagar, Abhijit V.
Rights Statement Label:
In Copyright
Source:
wp988r342

1903. Approaches to detect genetic effects that differ between two strata in genome-wide meta-analyses: Recommendations based on a systematic evaluation

Title Tesim:
Approaches to detect genetic effects that differ between two strata in genome-wide meta-analyses: Recommendations based on a systematic evaluation
Creator:
Kutalik, Zoltán, Justice, Anne E., Winkler, Thomas W., Heid, Iris M., Kronenberg, Florian, and Cupples, L. Adrienne
Date of publication:
2017
Abstract Tesim:
Genome-wide association meta-analyses (GWAMAs) conducted separately by two strata have identified differences in genetic effects between strata, such as sex-differences for body fat distribution. However, there are several approaches to identify such differences and an uncertainty which approach to use. Assuming the availability of stratified GWAMA results, we compare various approaches to identify between-strata differences in genetic effects. We evaluate type I error and power via simulations and analytical comparisons for different scenarios of strata designs and for different types of between-strata differences. For strata of equal size, we find that the genome-wide test for difference without any filtering is the best approach to detect stratum-specific genetic effects with opposite directions, while filtering for overall association followed by the difference test is best to identify effects that are predominant in one stratum. When there is no a priori hypothesis on the type of difference, a combination of both approaches can be recommended. Some approaches violate type I error control when conducted in the same data set. For strata of unequal size, the best approach depends on whether the genetic effect is predominant in the larger or in the smaller stratum. Based on real data from GIANT (>175 000 individuals), we exemplify the impact of the approaches on the detection of sex-differences for body fat distribution (identifying up to 10 loci). Our recommendations provide tangible guidelines for future GWAMAs that aim at identifying between-strata differences. A better understanding of such effects will help pinpoint the underlying mechanisms.
Resource type:
Article
Affiliation Label Tesim:
Department of Epidemiology
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/2kag-p357
Identifier:
Onescience id: 0ec4caa66fd318fbcb3e47329fb9718bda7c6eae, PMCID: PMC5531538, Publisher DOI: https://doi.org/10.1371/journal.pone.0181038, and PMID: 28749953
ISSN:
1932-6203
Journal Issue:
7
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Genetic loci, Sexual dimorphism, Meta-analysis, Genome-wide association studies, Consortia, Test statistics, Phenotypes, and Analysts
Language Label:
English
ORCID:
Other Affiliation:
Institute of Social and Preventive Medicine; CHUV-UNIL, Swiss Institute of Bioinformatics, Department of Genetic Epidemiology; University of Regensburg, Division of Genetic Epidemiology; Department of Medical Genetics; Molecular and Clinical Pharmacology; Medical University of Innsbruck, NHLBI Framingham Heart Study, and Department of Biostatistics; Boston University School of Public Health
Page Start:
e0181038
Person:
Kutalik, Zoltán, Justice, Anne E., Winkler, Thomas W., Heid, Iris M., Kronenberg, Florian, and Cupples, L. Adrienne
Rights Statement Label:
In Copyright
Source:
1g05fh69z

1904. Anthropological contributions to historical ecology: 50 questions, infinite prospects

Title Tesim:
Anthropological contributions to historical ecology: 50 questions, infinite prospects
Creator:
Petek, Nik, Anderson, Eugene N., Sinclair, Paul, Vamosi, Jana C., Ekblom, Anneli, Ibragimow, Aleksandra, Crumley, Carole L., LeCompte, Joyce K., Armstrong, Chelsey Geralda, Nabess, Carly, Walshaw, Sarah, Marks-Block, Tony, McKechnie, Iain, Shoemaker, Anna C., Podruczny, Grzegorz, Szabó, Péter, Lane, Paul J., McAlvay, Alex C., Morales, Erendira Quintana, Boles, Oliver J., Awâsis, Sakihitowin, and Gibbons, Kevin S.
Date of publication:
2017
Abstract Tesim:
This paper presents the results of a consensus-driven process identifying 50 priority research questions for historical ecology obtained through crowdsourcing, literature reviews, and in-person workshopping. A deliberative approach was designed to maximize discussion and debate with defined outcomes. Two in-person workshops (in Sweden and Canada) over the course of two years and online discussions were peer facilitated to define specific key questions for historical ecology from anthropological and archaeological perspectives. The aim of this research is to showcase the variety of questions that reflect the broad scope for historical-ecological research trajectories across scientific disciplines. Historical ecology encompasses research concerned with decadal, centennial, and millennial human-environmental interactions, and the consequences that those relationships have in the formation of contemporary landscapes. Six interrelated themes arose from our consensus-building workshop model: (1) climate and environmental change and variability; (2) multi-scalar, multi-disciplinary; (3) biodiversity and community ecology; (4) resource and environmental management and governance; (5) methods and applications; and (6) communication and policy. The 50 questions represented by these themes highlight meaningful trends in historical ecology that distill the field down to three explicit findings. First, historical ecology is fundamentally an applied research program. Second, this program seeks to understand long-term human-environment interactions with a focus on avoiding, mitigating, and reversing adverse ecological effects. Third, historical ecology is part of convergent trends toward transdisciplinary research science, which erodes scientific boundaries between the cultural and natural.
Resource type:
Article
Affiliation Label Tesim:
Department of Anthropology
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/ty0b-na57
Identifier:
Onescience id: c0feaf0906f12008a7194013d75e5ed140400914, Publisher DOI: https://doi.org/10.1371/journal.pone.0171883, PMID: 28235093, and PMCID: PMC5325225
ISSN:
1932-6203
Journal Issue:
2
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Biodiversity, Environmental change, Canada, Cultural, Consensus development, Crowdsourcing, Anthropology, Article, Ecosystem, 20th Century, 21st Century, Climate, History, Community ecology, Applied research, Ecology, Cultural anthropology, Case report, and Environmental management
Language Label:
English
ORCID:
Other Affiliation:
Department of Archaeology and Ancient History; Uppsala University, Department of Anthropology; University California Santa Barbara, Department of Biological Sciences; University of Calgary, Polish-German Research Institute; Adams Mickiewicz University in Poznań; European University, Integrated History of Future of People on Earth (IHOPE) Initiative, Independent Scholar, Department of Archaeology; Simon Fraser University, Department of Anthropology; University of Northern British Columbia, Department of History; Simon Fraser University, Department of Anthropology; Stanford University, Hakai Institute, Department of Anthropology; University of Victoria, Department of Vegetation Ecology; Institute of Botany of the Czech Academy of Sciences, School of Geography; Archaeology and Environmental Studies; University of the Witwatersrand, Department of Botany; University of Wisconsin - Madison, Department of Anthropology; Rice University, Institute of Archaeology; University College London, Department of Geography; Western University, Atlohsa Native Family Healing Services; Canada, and Department of Anthropology; University of Maryland
Page Start:
e0171883
Person:
Petek, Nik, Anderson, Eugene N., Sinclair, Paul, Vamosi, Jana C., Ekblom, Anneli, Ibragimow, Aleksandra, Crumley, Carole L., LeCompte, Joyce K., Armstrong, Chelsey Geralda, Nabess, Carly, Walshaw, Sarah, Marks-Block, Tony, McKechnie, Iain, Shoemaker, Anna C., Podruczny, Grzegorz, Szabó, Péter, Lane, Paul J., McAlvay, Alex C., Morales, Erendira Quintana, Boles, Oliver J., Awâsis, Sakihitowin, and Gibbons, Kevin S.
Rights Statement Label:
In Copyright
Source:
t722hg10h

1905. An evidence-based evaluation of transferrable skills and job satisfaction for science PhDs

Title Tesim:
An evidence-based evaluation of transferrable skills and job satisfaction for science PhDs
Creator:
O'Connell, Anna B., Hall, Joshua D., Harrell, Jessica R., Sinche, Melanie, Brennwald, Patrick J., Brandt, Patrick D., Layton, Rebekah L., Freeman, Ashalla M., and Cook, Jeanette Gowen
Date of publication:
2017
Abstract Tesim:
PhD recipients acquire discipline-specific knowledge and a range of relevant skills during their training in the life sciences, physical sciences, computational sciences, social sciences, and engineering. Empirically testing the applicability of these skills to various careers held by graduates will help assess the value of current training models. This report details results of an Internet survey of science PhDs (n = 8099) who provided ratings for fifteen transferrable skills. Indeed, analyses indicated that doctoral training develops these transferrable skills, crucial to success in a wide range of careers including research-intensive (RI) and non-research-intensive (NRI) careers. Notably, the vast majority of skills were transferrable across both RI and NRI careers, with the exception of three skills that favored RI careers (creativity/innovative thinking, career planning and awareness skills, and ability to work with people outside the organization) and three skills that favored NRI careers (time management, ability to learn quickly, ability to manage a project). High overall rankings suggested that graduate training imparted transferrable skills broadly. Nonetheless, we identified gaps between career skills needed and skills developed in PhD training that suggest potential areas for improvement in graduate training. Therefore, we suggest that a two-pronged approach is crucial to maximizing existing career opportunities for PhDs and developing a career-conscious training model: 1) encouraging trainees to recognize their existing individual skill sets, and 2) increasing resources and programmatic interventions at the institutional level to address skill gaps. Lastly, comparison of job satisfaction ratings between PhD-trained employees in both career categories indicated that those in NRI career paths were just as satisfied in their work as their RI counterparts. We conclude that PhD training prepares graduates for a broad range of satisfying careers, potentially more than trainees and program leaders currently appreciate.
Resource type:
Article
Affiliation Label Tesim:
Department of Cell Biology and Physiology
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/ec90-5f24
Identifier:
Onescience id: 8584dd069ed3a2fb4b4efd42793aedddab060745, PMID: 28931079, PMCID: PMC5607200, and Publisher DOI: https://doi.org/10.1371/journal.pone.0185023
ISSN:
1932-6203
Journal Issue:
9
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Science, Training Support, Career Choice, Humans, Job Satisfaction, Biomedical Research, and Education, Graduate
Language Label:
English
ORCID:
and 0000-0001-7113-1348
Other Affiliation:
Department of Cell Biology and Physiology
Page Start:
e0185023
Person:
O'Connell, Anna B., Hall, Joshua D., Harrell, Jessica R., Sinche, Melanie, Brennwald, Patrick J., Brandt, Patrick D., Layton, Rebekah L., Freeman, Ashalla M., and Cook, Jeanette Gowen
Rights Statement Label:
In Copyright
Source:
fb494f625

1906. Alterations in airway microbiota in patients with PaO2/FiO2 ratio ≤ 300 after burn and inhalation injury

Title Tesim:
Alterations in airway microbiota in patients with PaO2/FiO2 ratio ≤ 300 after burn and inhalation injury
Creator:
McCullough, Shaun D., Yourstone, Scott, Cairns, Bruce A., Jones, Corbin D., Jones, Samuel W., Jaspers, Ilona, Diaz-Sanchez, David, and Walsh, Dana M.
Date of publication:
2017
Abstract Tesim:
Injury to the airways after smoke inhalation is a major mortality risk factor in victims of burn injuries, resulting in a 15–45% increase in patient deaths. Damage to the airways by smoke may induce acute respiratory distress syndrome (ARDS), which is partly characterized by hypoxemia in the airways. While ARDS has been associated with bacterial infection, the impact of hypoxemia on airway microbiota is unknown. Our objective was to identify differences in microbiota within the airways of burn patients who develop hypoxemia early after inhalation injury and those that do not using next-generation sequencing of bacterial 16S rRNA genes.
Resource type:
Article
Affiliation Label Tesim:
Department of Biology, Department of Surgery, Carolina Center for Genome Sciences, and University of North Carolina at Chapel Hill
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/3abb-kq56
Identifier:
PMID: 28358811, Publisher DOI: https://doi.org/10.1371/journal.pone.0173848, PMCID: PMC5373524, and Onescience id: 1a96b84b1fe0f5534dbeabbb77cb9a3c517cade4
ISSN:
1932-6203
Journal Issue:
3
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Middle Aged, Adolescent, Aged, Hypoxia, Longitudinal Studies, Male, Female, Burns, Inhalation, Infant, RNA, Ribosomal, 16S, Microbiota, North Carolina, Child, Humans, Child, Preschool, Adult, and Prospective Studies
Language Label:
English
ORCID:
Other Affiliation:
National Health and Environmental Effects Research Laboratory; U.S. Environmental Protection Agency, Curriculum in Bioinformatics and Computational Biology, Department of Surgery, UNC Lineberger Comprehensive Cancer Center, Curriculum in Genetics and Molecular Biology, Department of Pediatrics, and Center for Environmental Medicine, Asthma and Lung Biology
Page Start:
e0173848
Person:
McCullough, Shaun D., Yourstone, Scott, Cairns, Bruce A., Jones, Corbin D., Jones, Samuel W., Jaspers, Ilona, Diaz-Sanchez, David, and Walsh, Dana M.
Rights Statement Label:
In Copyright
Source:
pk02ch179

1907. ALC1/CHD1L, a chromatin-remodeling enzyme, is required for efficient base excision repair

Title Tesim:
ALC1/CHD1L, a chromatin-remodeling enzyme, is required for efficient base excision repair
Creator:
Hirota, Kouji, Takeda, Shunichi, Harada, Hiroshi, Pommier, Yves, Koike, Kaoru, Fujiike, Haruna, Nakamura, Jun, Murai, Junko, Tsuda, Masataka, Shimizu, Naoto, Yamamoto, Takashi, Asada, Ryuta, Sakuma, Tetsushi, Ooka, Masato, Agama, Keli, Nakazawa, Yuka, Yasui, Akira, Cho, Kosai, Hiraoka, Masahiro, Watanabe, Reiko, and Ogi, Tomoo
Date of publication:
2017
Abstract Tesim:
ALC1/CHD1L is a member of the SNF2 superfamily of ATPases carrying a macrodomain that binds poly(ADP-ribose). Poly(ADP-ribose) polymerase (PARP) 1 and 2 synthesize poly(ADP-ribose) at DNA-strand cleavage sites, promoting base excision repair (BER). Although depletion of ALC1 causes increased sensitivity to various DNA-damaging agents (H2O2, UV, and phleomycin), the role played by ALC1 in BER has not yet been established. To explore this role, as well as the role of ALC1’s ATPase activity in BER, we disrupted the ALC1 gene and inserted the ATPase-dead (E165Q) mutation into the ALC1 gene in chicken DT40 cells, which do not express PARP2. The resulting ALC1-/- and ALC1-/E165Q cells displayed an indistinguishable hypersensitivity to methylmethane sulfonate (MMS), an alkylating agent, and to H2O2, indicating that ATPase plays an essential role in the DNA-damage response. PARP1-/- and ALC1-/-/PARP1-/- cells exhibited a very similar sensitivity to MMS, suggesting that ALC1 and PARP1 collaborate in BER. Following pulse-exposure to H2O2, PARP1-/- and ALC1-/-/PARP1-/- cells showed similarly delayed kinetics in the repair of single-strand breaks, which arise as BER intermediates. To ascertain ALC1’s role in BER in mammalian cells, we disrupted the ALC1 gene in human TK6 cells. Following exposure to MMS and to H2O2, the ALC1-/- TK6 cell line showed a delay in single-strand-break repair. We therefore conclude that ALC1 plays a role in BER. Following exposure to H2O2,ALC1-/- cells showed compromised chromatin relaxation. We thus propose that ALC1 is a unique BER factor that functions in a chromatin context, most likely as a chromatin-remodeling enzyme.
Resource type:
Article
Affiliation Label Tesim:
Department of Environmental Sciences and Engineering
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/kwy9-bf30
Identifier:
Publisher DOI: https://doi.org/10.1371/journal.pone.0188320, PMID: 29149203, Onescience id: ff416da8e7f55497eaa64a764a449b805b9d8680, and PMCID: PMC5693467
ISSN:
1932-6203
Journal Issue:
11
Journal Title:
PloS One
Journal Volume:
12
Keyword:
DNA Helicases, Chromatin, B-Lymphocytes, Humans, Gene Expression Regulation, Chromatin Assembly and Disassembly, DNA-Binding Proteins, Animals, DNA Repair, Cell Line, Transformed, Hydrogen Peroxide, Cell Line, Tumor, Chickens, Methyl Methanesulfonate, and HeLa Cells
Language Label:
English
ORCID:
Other Affiliation:
Department of Chemistry; Tokyo Metropolitan University, Department of Radiation Genetics; Graduate School of Medicine; Kyoto University, Laboratory of Cancer Cell Biology; Radiation Biology Center; Kyoto University, Laboratory of Molecular Pharmacology; Developmental Therapeutics Branch; Center for Cancer Research; National Cancer Institute; National Institutes of Health, Department of Primary Care and Emergency Medicine; Kyoto University Graduate School of Medicine, Department of Mathematical and Life Sciences; Graduate School of Science; Hiroshima University, Department of Genetics; Research Institute of Environmental Medicine (RIeM); Nagoya University, Department of Genome Repair; Atomic Bomb Disease Institute; Nagasaki University Sakamoto, Division of Dynamic Proteome; Institute of Development; Aging and Cancer; Tohoku University, Department of Radiation Oncology; Japanese Red Cross Society Wakayama Medical Center, and National Institutes of Biomedical Innovation; Health and Nutrition
Page Start:
e0188320
Person:
Hirota, Kouji, Takeda, Shunichi, Harada, Hiroshi, Pommier, Yves, Koike, Kaoru, Fujiike, Haruna, Nakamura, Jun, Murai, Junko, Tsuda, Masataka, Shimizu, Naoto, Yamamoto, Takashi, Asada, Ryuta, Sakuma, Tetsushi, Ooka, Masato, Agama, Keli, Nakazawa, Yuka, Yasui, Akira, Cho, Kosai, Hiraoka, Masahiro, Watanabe, Reiko, and Ogi, Tomoo
Rights Statement Label:
In Copyright
Source:
08612t83c

1908. Admixture mapping of pelvic organ prolapse in African Americans from the Women’s Health Initiative Hormone Therapy trial

Title Tesim:
Admixture mapping of pelvic organ prolapse in African Americans from the Women’s Health Initiative Hormone Therapy trial
Creator:
Ward, Renee M., Wallace, Robert B., O'Sullivan, Mary J., North, Kari E., Qi, Lihong, Wu, Jennifer M., Aldrich, Melinda C., Edwards, Digna R. Velez, Gr, Mariaelisa, Giri, Ayush, Edwards, Todd L., Park, Amy J., Hartmann, Katherine E., and Nassir, Rami
Date of publication:
2017
Abstract Tesim:
Evidence suggests European American (EA) women have two- to five-fold increased odds of having pelvic organ prolapse (POP) when compared with African American (AA) women. However, the role of genetic ancestry in relation to POP risk is not clear. Here we evaluate the association between genetic ancestry and POP in AA women from the Women’s Health Initiative Hormone Therapy trial. Women with grade 1 or higher classification, and grade 2 or higher classification for uterine prolapse, cystocele or rectocele at baseline or during follow-up were considered to have any POP (N = 805) and moderate/severe POP (N = 156), respectively. Women with at least two pelvic exams with no indication for POP served as controls (N = 344). We performed case-only, and case-control admixture-mapping analyses using multiple logistic regression while adjusting for age, BMI, parity and global ancestry. We evaluated the association between global ancestry and POP using multiple logistic regression. European ancestry at the individual level was not associated with POP risk. Case-only and case-control local ancestry analyses identified two ancestry-specific loci that may be associated with POP. One locus (Chromosome 15q26.2) achieved empirically-estimated statistical significance and was associated with decreased POP odds (considering grade ≥2 POP) with each unit increase in European ancestry (OR: 0.35; 95% CI: 0.30, 0.57; p-value = 1.48x10-5). This region includes RGMA, a potent regulator of the BMP family of genes. The second locus (Chromosome 1q42.1-q42.3) was associated with increased POP odds with each unit increase in European ancestry (Odds ratio [OR]: 1.69; 95% confidence interval [CI]: 1.28, 2.22; p-value = 1.93x10-4). Although this region did not reach statistical significance after considering multiple comparisons, it includes potentially relevant genes including TBCE, and ACTA1. Unique non-overlapping European and African ancestry-specific susceptibility loci may be associated with increased POP risk.
Resource type:
Article
Affiliation Label Tesim:
Department of Epidemiology and Department of Obstetrics and Gynecology
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/f6bq-wy87
Identifier:
Onescience id: e555118aa7445278b72b4ac793ef400ac462ae17, Publisher DOI: https://doi.org/10.1371/journal.pone.0178839, PMID: 28582460, and PMCID: PMC5459562
ISSN:
1932-6203
Journal Issue:
6
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Nerve Tissue Proteins, Population groupings, Genetic Loci, Evolutionary Biology, African Americans, Molecular Biology Techniques, Rectocele, Gene Mapping, Alleles, Science, Uterine Prolapse, People and places, Molecular Biology, Women's Health, Human Genetics, Q, Molecular Chaperones, Genetics, Ethnicities, Biology and Life Sciences, Population Genetics, Medicine and Health Sciences, Research Article, Research and Analysis Methods, Humans, Actins, R, Medicine, Population Biology, Body Mass Index, Severity, and Chromosome Mapping
Language Label:
English
ORCID:
Other Affiliation:
Department of Obstetrics and Gynecology; Vanderbilt University; Medical Center, Department of Epidemiology; University of Iowa; College of Public Health, Department of Obstetrics and Gynecology; Miller School of Medicine, Division of Biostatistics; Department of Public Health Sciences; School of Medicine; University of California; Davis, Department of Thoracic Surgery; Vanderbilt University; Medical Center, Vanderbilt Genetics Institute; Vanderbilt University; Medical Center, Division of Epidemiology; Department of Medicine; Vanderbilt University; Medical Center, Vanderbilt Epidemiology Center; Institute for Medicine and Public Health; Vanderbilt University; Medical Center, Department of Obstetrics and Gynecology; Georgetown University; School of Medicine, Department of Biochemistry and Molecular Medicine; University of California; Davis, and Department of Internal Medicine; University of California; Davis
Page Start:
e0178839
Person:
Ward, Renee M., Wallace, Robert B., O'Sullivan, Mary J., North, Kari E., Qi, Lihong, Wu, Jennifer M., Aldrich, Melinda C., Edwards, Digna R. Velez, Gr, Mariaelisa, Giri, Ayush, Edwards, Todd L., Park, Amy J., Hartmann, Katherine E., and Nassir, Rami
Rights Statement Label:
In Copyright
Source:
3f462b54z

1909. Admixture mapping in the Hispanic Community Health Study/Study of Latinos reveals regions of genetic associations with blood pressure traits

Title Tesim:
Admixture mapping in the Hispanic Community Health Study/Study of Latinos reveals regions of genetic associations with blood pressure traits
Creator:
Reiner, Alex P., Hanson, Robert, Daviglus, Martha L., Thornton, Timothy A., Talavera, Gregory A., Baier, Leslie J., Levy, Daniel, Wassertheil-Smoller, Sylvia, Franceschini, Nora, Sofer, Tamar, Browning, Sharon R., Kobes, Sayuko, Cooper, Richard S., and Cai, Jianwen
Date of publication:
2017
Abstract Tesim:
Admixture mapping can be used to detect genetic association regions in admixed populations, such as Hispanics/Latinos, by estimating associations between local ancestry allele counts and the trait of interest. We performed admixture mapping of the blood pressure traits systolic and diastolic blood pressure (SBP, DBP), mean arterial pressure (MAP), and pulse pressure (PP), in a dataset of 12,116 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Hispanics/Latinos have three predominant ancestral populations (European, African, and Amerindian), for each of which we separately tested local ancestry intervals across the genome. We identified four regions that were significantly associated with a blood pressure trait at the genome-wide admixture mapping level. A 6p21.31 Amerindian ancestry association region has multiple known associations, but none explained the admixture mapping signal. We identified variants that completely explained this signal. One of these variants had p-values of 0.02 (MAP) and 0.04 (SBP) in replication testing in Pima Indians. A 11q13.4 Amerindian ancestry association region spans a variant that was previously reported (p-value = 0.001) in a targeted association study of Blood Pressure (BP) traits and variants in the vitamin D pathway. There was no replication evidence supporting an association in the identified 17q25.3 Amerindian ancestry association region. For a region on 6p12.3, associated with African ancestry, we did not identify any candidate variants driving the association. It may be driven by rare variants. Whole genome sequence data may be necessary to fine map these association signals, which may contribute to disparities in BP traits between diverse populations.
Resource type:
Article
Affiliation Label Tesim:
Department of Epidemiology and Department of Biostatistics
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/pchc-4641
Identifier:
Publisher DOI: https://doi.org/10.1371/journal.pone.0188400, PMID: 29155883, PMCID: PMC5695820, and Onescience id: ad75aa82731af4eced5f7ec9722da7c147c0ea04
ISSN:
1932-6203
Journal Issue:
11
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Chromosome Mapping, Molecular Biology Techniques, Genetic Mapping, Genome Analysis, Variant Genotypes, Blood Pressure, Heredity, Medicine and Health Sciences, Genomic Signal Pro, Human Genetics, Molecular Biology, Genomics, Biology and Life Sciences, Cell Signaling, Computational Biology, People and places, Mexican People, Population groupings, Genetics, Cell Biology, Signal Transduction, Latin American people, Gene Mapping, Ethnicities, Genome-Wide Association Studies, Gene Identification and Analysis, and Vascular Medicine
Language Label:
English
ORCID:
Other Affiliation:
Division of Public Health Sciences; Fred Hutchinson Cancer Research Center, Phoenix Epidemiology and Clinical Research Branch; NIDDK; NIH, Institute for Minority Health Research; University of Illinois at Chicago, Feinberg School of Medicine; Northwestern University, Department of Biostatistics; University of Washington, Division of Health Promotion and Behavioral Science; San Diego State University, Population Sciences Branch; National Heart; Lung; and Blood Institute; National Institutes of Health, Framingham Heart Study, Department of Epidemiology and Population Health; Albert Einstein College of Medicine, Department of Medicine; Harvard Medical School, Division of Sleep and Circadian Disorders; Brigham and Women’s Hospital, and Department of Public Health Sciences; Stritch School of Medicine; Loyola University Chicago
Page Start:
e0188400
Person:
Reiner, Alex P., Hanson, Robert, Daviglus, Martha L., Thornton, Timothy A., Talavera, Gregory A., Baier, Leslie J., Levy, Daniel, Wassertheil-Smoller, Sylvia, Franceschini, Nora, Sofer, Tamar, Browning, Sharon R., Kobes, Sayuko, Cooper, Richard S., and Cai, Jianwen
Rights Statement Label:
In Copyright
Source:
9593v1617

1910. Adaptations of an RNA virus to increasing thermal stress

Title Tesim:
Adaptations of an RNA virus to increasing thermal stress
Creator:
Cierra, M Leon Guerrero, Whang, Stella G, Singhal, Sonia, Kerr, Benjamin, Busch, Hannah G, and McClure, Erin M
Date of publication:
2017
Abstract Tesim:
Environments can change in incremental fashions, where a shift from one state to another occurs over multiple organismal generations. The rate of the environmental change is expected to influence how and how well populations adapt to the final environmental state. We used a model system, the lytic RNA bacteriophage Φ6, to investigate this question empirically. We evolved viruses for thermostability by exposing them to heat shocks that increased to a maximum temperature at different rates. We observed increases in the ability of many heat-shocked populations to survive high temperature heat shocks. On their first exposure to the highest temperature, populations that experienced a gradual increase in temperature had higher average survival than populations that experienced a rapid temperature increase. However, at the end of the experiment, neither the survival of populations at the highest temperature nor the number of mutations per population varied significantly according to the rate of thermal change. We also evaluated mutations from the endpoint populations for their effects on viral thermostability and growth. As expected, some mutations did increase viral thermostability. However, other mutations decreased thermostability but increased growth rate, suggesting that benefits of an increased replication rate may have sometimes outweighed the benefits of enhanced thermostability. Our study highlights the importance of considering the effects of multiple selective pressures, even in environments where a single factor changes.
Resource type:
Article
Affiliation Label Tesim:
Department of Biology
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/3k5k-by88
Identifier:
Onescience id: f99f7f13f444f7ff0e59d535af6bfd7569acde1a, PMID: 29267297, PMCID: PMC5739421, and Publisher DOI: https://doi.org/10.1371/journal.pone.0189602
ISSN:
1932-6203
Journal Issue:
12
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Bacteriology, Viral Evolution, Mutation, Hot Temperature, Microbial Mutation, Population Genetics, Bacteriophage phi 6, Organismal Evolution, Microbial Evolution, Population Biology, Q, Adaptation, Microbiology, Bacterial Evolution, Medicine, Evolutionary Adaptation, Research Article, Biology and Life Sciences, Organisms, Virology, R, Stress, Evolutionary Processes, Physiological, Viral Replication, Bacteriophages, Substitution Mutation, Viruses, Science, Evolutionary Biology, and Genetics
Language Label:
English
ORCID:
Other Affiliation:
Department of Biology; University of Washington
Page Start:
e0189602
Person:
Cierra, M Leon Guerrero, Whang, Stella G, Singhal, Sonia, Kerr, Benjamin, Busch, Hannah G, and McClure, Erin M
Rights Statement Label:
In Copyright
Source:
jm214v47w