| 1. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 3. |
- Graham, Jesse R., et al.
(författare)
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The pipeline project: Pre-publication independent replications of a single laboratory's research pipeline
- 2016
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Ingår i: Journal of Experimental Social Psychology. - : Elsevier. - 1096-0465 .- 0022-1031. ; 66, s. 55-67
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Tidskriftsartikel (refereegranskat)abstract
- This crowdsourced project introduces a collaborative approach to improving the reproducibility of scientific research, in which findings are replicated in qualified independent laboratories before (rather than after) they are published. Our goal is to establish a non-adversarial replication process with highly informative final results. To illustrate the Pre-Publication Independent Replication (PPIR) approach, 25 research groups conducted replications of all ten moral judgment effects which the last author and his collaborators had “in the pipeline” as of August 2014. Six findings replicated according to all replication criteria, one finding replicated but with a significantly smaller effect size than the original, one finding replicated consistently in the original culture but not outside of it, and two findings failed to find support. In total, 40% of the original findings failed at least one major replication criterion. Potential ways to implement and incentivize pre-publication independent replication on a large scale are discussed.
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| 4. |
- Washburn, Anthony N., et al.
(författare)
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Data from a pre-publication independent replication initiative examining ten moral judgement effects
- 2016
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Ingår i: Scientific Data. - : Nature Research (part of Springer Nature): Fully open access journals / Nature Publishing Group. - 2052-4463. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- We present the data from a crowdsourced project seeking to replicate findings in independent laboratories before (rather than after) they are published. In this Pre-Publication Independent Replication (PPIR) initiative, 25 research groups attempted to replicate 10 moral judgment effects from a single laboratory's research pipeline of unpublished findings. The 10 effects were investigated using online/lab surveys containing psychological manipulations (vignettes) followed by questionnaires.
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| 5. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 6. |
- Clark, Samuel J, et al.
(författare)
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Cardiometabolic disease risk and HIV status in rural South Africa : establishing a baseline
- 2015
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Ingår i: BMC Public Health. - : BioMed Central. - 1471-2458. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: To inform health care and training, resource and research priorities, it is essential to establish how non-communicable disease risk factors vary by HIV-status in high HIV burden areas; and whether long-term anti-retroviral therapy (ART) plays a modifying role. Methods: As part of a cohort initiation, we conducted a baseline HIV/cardiometabolic risk factor survey in 2010-2011 using an age-sex stratified random sample of ages 15+ in rural South Africa. We modelled cardiometabolic risk factors and their associations by HIV-status and self-reported ART status for ages 18+ using sex-stratified logistic regression models. Results: Age-standardised HIV prevalence in women was 26% (95% CI 24-28%) and 19% (95% CI 17-21) in men. People with untreated HIV were less likely to have a high waist circumference in both women (OR 0.67; 95% CI 0.52-0.86) and men (OR 0.42; 95% CI 0.22-0.82). Untreated women were more likely to have low HDL and LDL, and treated women high triglycerides. Cardiometabolic risk factors increased with age except low HDL. The prevalence of hypertension was high (40% in women; 30% in men). Conclusions: Sub-Saharan Africa is facing intersecting epidemics of HIV and hypertension. In this setting, around half the adult population require long-term care for at least one of HIV, hypertension or diabetes. Together with the adverse effects that HIV and its treatment have on lipids, this may have serious implications for the South African health care system. Monitoring of the interaction of HIV, ART use, and cardiometabolic disease is needed at both individual and population levels.
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| 7. |
- Gomez-Olive, Francesc Xavier, et al.
(författare)
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Prevalence of HIV among those 15 and older in rural South Africa
- 2013
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Ingår i: AIDS Care. - : Taylor & Francis. - 0954-0121 .- 1360-0451. ; 25:9, s. 1122-1128
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Tidskriftsartikel (refereegranskat)abstract
- A greater knowledge of the burden of HIV in rural areas of Southern Africa is needed, especially among older adults. We conducted a cross-sectional biomarker survey in the rural South African Agincourt Health and Socio-demographic Surveillance site in 2010-2011 and estimated HIV prevalence and risk factors. Using an age-sex stratified random sample of ages 15+, a total of 5037 (65.7%) of a possible 7662 individuals were located and 4362 (86.6%) consented to HIV testing. HIV prevalence was high (19.4%) and characterized by a large gender gap (10.6% for men and 23.9% for women). Rates peaked at 45.3% among men and 46.1% among women - both at ages 35-39. Compared with a similar study in the rural KwaZulu-Natal Province, South Africa, peak prevalence occurred at later ages, and HIV prevalence was higher among older adults - with rates above 15% for men and 10% for women through to age 70. High prevalence continues to characterize Southern Africa, and recent evidence confirms that older adults cannot be excluded from policy considerations. The high prevalence among older adults suggests likely HIV infection at older ages. Prevention activities need to expand to older adults to reduce new infections. Treatment will be complicated by increased risk of noncommunicable diseases and by increasing numbers of older people living with HIV.
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| 8. |
- Gretarsdottir, Solveig, et al.
(författare)
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Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:8, s. 71-692
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Tidskriftsartikel (refereegranskat)abstract
- We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 x 10(-10). In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 10(-5)) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases-that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.
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| 9. |
- Houle, Brian, et al.
(författare)
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Let's Talk about Sex, Maybe : Interviewers, Respondents, and Sexual Behavior Reporting in Rural South Africa
- 2016
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Ingår i: Field Methods. - 1525-822X .- 1552-3969. ; 28:2, s. 112-132
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Tidskriftsartikel (refereegranskat)abstract
- Researchers are often skeptical of sexual behavior surveys: Respondents may lie or forget details of their intimate lives, and interviewers may exercise authority in how they capture responses. We use data from a 2010-2011 cross-sectional sexual behavior survey in rural South Africa to explore who says what to whom about their sexual lives. Results show an effect of fieldworker age across outcomes: Respondents report safer, more responsible sexual behavior to older fieldworkers, and an effect of fieldworker sex; men report more sexual partners to female fieldworkers. Understanding fieldworker effects on the production of sexual behavior survey data serves methodological and analytical goals.
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| 10. |
- Houle, Brian, et al.
(författare)
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Sexual behavior and HIV risk across the life course in rural South Africa : trends and comparisons
- 2018
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Ingår i: AIDS Care. - : ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD. - 0954-0121 .- 1360-0451. ; 30:11, s. 1435-1443
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Tidskriftsartikel (refereegranskat)abstract
- There is limited information about sexual behavior among older Africans, which is problematic given high HIV rates among older adults. We use a population-based survey among people aged 15-80+ to examine the prevalence of sexual risk and protective behaviors in the context of a severe HIV epidemic. We focus on variation across the life course, gender and HIV serostatus to compare the similarities and differences of young, middle aged, and older adults. Younger adults continue to be at risk of HIV, with potential partners being more likely to have been diagnosed with an STI and more likely to have HIV, partner change is high, and condom use is low. Middle aged and older adults engage in sexual behavior that makes them vulnerable at older ages, including extramarital sex, low condom use, and cross-generational sex with people in age groups with the highest rates of HIV. We find insignificant differences between HIV positive and negative adults' reports of recent sexual activity. This study provides new information on sexual behavior and HIV risk across the life course in rural South Africa to inform HIV prevention and treatment programing.
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