| 1771. |
- Rask, Eva, 1958-, et al.
(författare)
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Tissue-specific dysregulation of cortisol metabolism in human obesity
- 2001
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Williams & Wilkins Co.. - 0021-972X .- 1945-7197. ; 86:3, s. 1418-1421
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Tidskriftsartikel (refereegranskat)abstract
- Cortisol has been implicated as a pathophysiological mediator in idiopathic obesity, but circulating cortisol concentrations are not consistently elevated. The tissue-specific responses to cortisol may be influenced as much by local pre-receptor metabolism as by circulating concentrations. For example, in liver and adipose tissue cortisol is regenerated from inactive cortisone by 11 beta -hydroxysteroid dehydrogenase type 1 (11 beta -HSD1). In obese Zucker rats 11 beta -HSD1 activity is reduced in liver but enhanced in adipose tissue. This study addressed whether the same tissue-specific disruption of cortisol metabolism occurs in human obesity. 34 men were recruited from the MONICA population study in Northern Sweden to represent a wide range of body composition and insulin sensitivity. Plasma cortisol was measured at 0830h and 1230h, after overnight low-dose dexamethasone suppression, after intravenous corticotropin releasing hormone (CRH), and after oral cortisone administration. Urinary cortisol metabolites were measured in a 24 h sample. A subcutaneous fat biopsy was obtained from le participants to measure cortisol metabolism in vitro. Higher body mass index was associated with increased total cortisol metabolite excretion (r=0.47, p<0.01), but lower plasma cortisol at 1230 h and after dexamethasone, and no difference in response to CRH. Obese men excreted a greater proportion of glucocorticoid as metabolites of cortisone rather than cortisol (r=0.43, p<0.02), and converted less cortisone to cortisol after oral administration (r=-0.49, p<0.01), suggesting impaired hepatic 11-HSD1 activity. By contrast, in vitro 11 beta -HSD1 activity in subcutaneous adipose tissue was markedly enhanced in obese men (r=0.66, p<0.01). We conclude that in obesity, reactivation of cortisone to cortisol by 11-HSD1 in liver is impaired, so that plasma cortisol levels tend to fall, and there may be a compensatory increase in cortisol secretion mediated by a normally functioning hypothalamic-pituitary-adrenal axis. However, changes in 11 beta -HSD1 are tissue-specific: strikingly enhanced reactivation of cortisone to cortisol in subcutaneous adipose tissue may exacerbate obesity; and it may be beneficial to inhibit this enzyme in adipose tissue in obese patients.
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| 1772. |
- Rautenberg, Tamlyn A., et al.
(författare)
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Determinants of health-related quality of life in people with Human Immunodeficiency Virus, failing first-line treatment in Africa
- 2023
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Ingår i: Health and Quality of Life Outcomes. - 1477-7525. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Antiretroviral treatment improves health related quality of life (HRQoL) of people with human immunodeficiency virus (PWH). However, one third initiating first-line treatment experience virological failure and the determinants of HRQoL in this key population are unknown. Our study aims to identify determinants of among PWH failing antiretroviral treatment in sub-Saharan Africa. Methods: We analysed data from a cohort of PWH having virological failure (> 1,000 copies/mL) on first-line ART in South Africa and Uganda. We measured HRQoL using the EuroQOL EQ-5D-3L and used a two-part regression model to obtain by-country analyses for South Africa and Uganda. The first part identifies risk factors that were associated with the likelihood of participants reporting perfect health (utility = 1) versus non-perfect health (utility < 1). The second part identifies risk factors that were associated with the EQ-5 L-3L utility scores for participants reporting non-perfect health. We performed sensitivity analyses to compare the results between the two-part model using tobit models and ordinary least squares regression. Results: In both countries, males were more likely to report perfect health and participants with at least one comorbidity were less likely to report perfect health. In South Africa, participants with side effects and in Uganda those with opportunistic infections were also less likely to report perfect health. In Uganda, participants with 100% ART adherence were more likely to report perfect health. In South Africa, high HIV viral load, experiencing ART side effects, and the presence of opportunistic infections were each associated with lower HRQoL, whereas participants with 100% ART adherence reported higher HRQoL. In Uganda participants with lower CD4 count had lower HRQoL. Conclusion: Markers of advanced disease (opportunistic infection, high viral load, low CD4), side effects, comorbidities and lack of ART adherence negatively impacted HRQoL for PWH experiencing virological failure. Trial registration: ClinicalTrials.gov: NCT02787499.
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| 1773. |
- Rautenberg, Tamlyn A., et al.
(författare)
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Seemingly Unrelated Regression Analysis of the Cost and Health-Related Quality of Life Outcomes of the REVAMP Randomized Clinical Trial
- 2023
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Ingår i: Value in Health Regional Issues. - : Elsevier BV. - 2212-1099. ; 35, s. 42-47
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to evaluate the 9-month cost and health-related quality of life (HRQOL) outcomes of resistance versus viral load testing strategies to manage virological failure in low-middle income countries. Methods: We analyzed secondary outcomes from the REVAMP clinical trial: a pragmatic, open label, parallel-arm randomized trial investigating resistance versus viral load testing for individuals failing first-line treatment in South Africa and Uganda. We collected resource data, valued according to local cost data and used the 3-level version of EQ-5D to measure HRQOL at baseline and 9 months. We applied seemingly unrelated regression equations to account for the correlation between cost and HRQOL. We conducted intention-to-treat analyses with multiple imputation using chained equations for missing data and performed sensitivity analyses using complete cases. Results: For South Africa, resistance testing and opportunistic infections were associated with statistically significantly higher total costs, and virological suppression was associated with lower total cost. Higher baseline utility, higher cluster of differentiation 4 (CD4) count, and virological suppression were associated with better HRQOL. For Uganda, resistance testing and switching to second-line treatment were associated with higher total cost, and higher CD4 was associated with lower total cost. Higher baseline utility, higher CD4 count, and virological suppression were associated with better HRQOL. Sensitivity analyses of the complete-case analysis confirmed the overall results. Conclusion: Resistance testing showed no cost or HRQOL advantage in South Africa or Uganda over the 9-month REVAMP clinical trial.
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| 1774. |
- Reddington, C. L., et al.
(författare)
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THE GLOBAL AEROSOL SYNTHESIS AND SCIENCE PROJECT (GASSP) : Measurements and Modeling to Reduce Uncertainty
- 2017
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:9, s. 1857-1877
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Tidskriftsartikel (refereegranskat)abstract
- The largest uncertainty in the historical radiative forcing of climate is caused by changes in aerosol particles due to anthropogenic activity. Sophisticated aerosol microphysics processes have been included in many climate models in an effort to reduce the uncertainty. However, the models are very challenging to evaluate and constrain because they require extensive in situ measurements of the particle size distribution, number concentration, and chemical composition that are not available from global satellite observations. The Global Aerosol Synthesis and Science Project (GASSP) aims to improve the robustness of global aerosol models by combining new methodologies for quantifying model uncertainty, to create an extensive global dataset of aerosol in situ microphysical and chemical measurements, and to develop new ways to assess the uncertainty associated with comparing sparse point measurements with low-resolution models. GASSP has assembled over 45,000 hours of measurements from ships and aircraft as well as data from over 350 ground stations. The measurements have been harmonized into a standardized format that is easily used by modelers and nonspecialist users. Available measurements are extensive, but they are biased to polluted regions of the Northern Hemisphere, leaving large pristine regions and many continental areas poorly sampled. The aerosol radiative forcing uncertainty can be reduced using a rigorous model-data synthesis approach. Nevertheless, our research highlights significant remaining challenges because of the difficulty of constraining many interwoven model uncertainties simultaneously. Although the physical realism of global aerosol models still needs to be improved, the uncertainty in aerosol radiative forcing will be reduced most effectively by systematically and rigorously constraining the models using extensive syntheses of measurements.
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| 1775. |
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| 1776. |
- Regmi, P., et al.
(författare)
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The future of WRRF modelling - Outlook and challenges
- 2019
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Ingår i: Water Science and Technology. - : IWA Publishing. - 0273-1223 .- 1996-9732. ; 79:1, s. 3-14
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Tidskriftsartikel (refereegranskat)abstract
- The wastewater industry is currently facing dramatic changes, shifting away from energy-intensive wastewater treatment towards low-energy, sustainable technologies capable of achieving energy positive operation and resource recovery. The latter will shift the focus of the wastewater industry to how one could manage and extract resources from the wastewater, as opposed to the conventional paradigm of treatment. Debatable questions arise: Can the more complex models be calibrated, or will additional unknowns be introduced? After almost 30 years using well-known International Water Association (IWA) models, should the community move to other components, processes, or model structures like 'black box' models, computational fluid dynamics techniques, etc.? Can new data sources - e.g. on-line sensor data, chemical and molecular analyses, new analytical techniques, off-gas analysis - keep up with the increasing process complexity? Are different methods for data management, data reconciliation, and fault detection mature enough for coping with such a large amount of information? Are the available calibration techniques able to cope with such complex models? This paper describes the thoughts and opinions collected during the closing session of the 6th IWA/WEF Water Resource Recovery Modelling Seminar 2018. It presents a concerted and collective effort by individuals from many different sectors of the wastewater industry to offer past and present insights, as well as an outlook into the future of wastewater modelling.
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| 1777. |
- Rendle, B. M., et al.
(författare)
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The K2 Galactic Caps Project - going beyond the Kepler field and ageing the Galactic disc
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 490:4, s. 4465-4480
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of data from spectroscopic and astrometric surveys have led to conflicting results concerning the vertical characteristics of the Milky Way. Ages are often used to provide clarity, but typical uncertainties of >40 per cent from photometry restrict the validity of the inferences made. Using the Kepler APOKASC sample for context, we explore the global population trends of two K2 campaign fields (3 and 6), which extend further vertically out of the Galactic plane than APOKASC. We analyse the properties of red giant stars utilizing three asteroseismic data analysis methods to cross-check and validate detections. The Bayesian inference tool PARAM is used to determine the stellar masses, radii, and ages. Evidence of a pronounced red giant branch bump and an [a/Fe] dependence on the position of the red clump is observed from the K2 fields radius distribution. Two peaks in the age distribution centred at similar to 5 and similar to 12 Gyr are found using a sample with sigma(age) < 35 per cent. In comparison with Kepler, we find the older peak to be more prominent for K2. This age bimodality is also observed based on a chemical selection of low-[alpha/Fe] (<= 0.1) and high-[alpha/Fe] (>0.1) stars. As a function of vertical distance from the Galactic mid-plane (|Z|), the age distribution shows a transition from a young to old stellar population with increasing |Z| for the K2 fields. Further coverage of campaign targets with high-resolution spectroscopy is required to increase the yield of precise ages achievable with asteroseismology.
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| 1778. |
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| 1779. |
- Richardson, R. T., et al.
(författare)
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A reference cytochrome c oxidase subunit I database curated for hierarchical classification of arthropod metabarcoding data
- 2018
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Ingår i: Peerj. - : PeerJ. - 2167-8359. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Metabarcoding is a popular application which warrants continued methods optimization. To maximize barcoding inferences, hierarchy-based sequence classification methods are increasingly common. We present methods for the construction and curation of a database designed for hierarchical classification of a 157 bp barcoding region of the arthropod cytochrome c oxidase subunit I (COI) locus. We produced a comprehensive arthropod COI amplicon dataset including annotated arthropod COI sequences and COI sequences extracted from arthropod whole mitochondrion genomes, the latter of which provided the only source of representation for Zoraptera, Callipodida and Holothyrida. The database contains extracted sequences of the target amplicon from all major arthropod clades, including all insect orders, all arthropod classes and Onychophora, Tardigrada and Mollusca outgroups. During curation, we extracted the COI region of interest from approximately 81 percent of the input sequences, corresponding to 73 percent of the genus-level diversity found in the input data. Further, our analysis revealed a high degree of sequence redundancy within the NCBI nucleotide database, with a mean of approximately 11 sequence entries per species in the input data. The curated, low-redundancy database is included in the Metaxa2 sequence classification software (http://microbiolognse/software/metaxa2/). Using this database with the Metaxa2 classifier, we performed a cross-validation analysis to characterize the relationship between the Metaxa2 reliability score, an estimate of classification confidence, and classification error probability. We used this analysis to select a reliability score threshold which minimized error. We then estimated classification sensitivity, false discovery rate and overclassification, the propensity to classify sequences from taxa not represented in the reference database. Our work will help researchers design and evaluate classification databases and conduct metabarcoding on arthropods and alternate taxa.
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| 1780. |
- Richardson, Rodney T, et al.
(författare)
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Evaluating and Optimizing the Performance of Software Commonly Used for the Taxonomic Classification of DNA Sequence Data
- 2017
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 17:4, s. 760-769
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Tidskriftsartikel (refereegranskat)abstract
- The taxonomic classification of DNA sequences has become a critical component of numerous ecological research applications; however, few studies have evaluated the strengths and weaknesses of commonly used sequence classification approaches. Further, the methods and software available for sequence classification are diverse, creating an environment in which it may be difficult to determine the best course of action and the tradeoffs made using different classification approaches. Here, we provide an in silico evaluation of three DNA sequence classifiers, the RDP Naïve Bayesian Classifier, RTAX and UTAX. Further, we discuss the results, merits and limitations of both the classifiers and our method of classifier evaluation. Our methods of comparison are simple, yet robust, and will provide researchers a methodological and conceptual foundation for making such evaluations in a variety of research situations. Generally, we found a considerable trade-off between accuracy and sensitivity for the classifiers tested, indicating a need for further improvement of sequence classification tools.
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