| 1. |
- Abdulla, Salim, et al.
(författare)
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Baseline data of parasite clearance in patients with falciparum malaria treated with an artemisinin derivative : an individual patient data meta-analysis
- 2015
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Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875 .- 1475-2875. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Artemisinin resistance in Plasmodium falciparum manifests as slow parasite clearance but this measure is also influenced by host immunity, initial parasite biomass and partner drug efficacy. This study collated data from clinical trials of artemisinin derivatives in falciparum malaria with frequent parasite counts to provide reference parasite clearance estimates stratified by location, treatment and time, to examine host factors affecting parasite clearance, and to assess the relationships between parasite clearance and risk of recrudescence during follow-up. Methods: Data from 24 studies, conducted from 1996 to 2013, with frequent parasite counts were pooled. Parasite clearance half-life (PC1/2) was estimated using the WWARN Parasite Clearance Estimator. Random effects regression models accounting for study and site heterogeneity were used to explore factors affecting PC1/2 and risk of recrudescence within areas with reported delayed parasite clearance (western Cambodia, western Thailand after 2000, southern Vietnam, southern Myanmar) and in all other areas where parasite populations are artemisinin sensitive. Results: PC1/2 was estimated in 6975 patients, 3288 of whom also had treatment outcomes evaluate d during 28-63 days follow-up, with 93 (2.8 %) PCR-confirmed recrudescences. In areas with artemisinin-sensitive parasites, the median PC1/2 following three-day artesunate treatment (4 mg/kg/day) ranged from 1.8 to 3.0 h and the proportion of patients with PC1/2 > 5 h from 0 to 10 %. Artesunate doses of 4 mg/kg/day decreased PC1/2 by 8.1 % (95 % CI 3.2-12.6) compared to 2 mg/kg/day, except in populations with delayed parasite clearance. PC1/2 was longer in children and in patients with fever or anaemia at enrolment. Long PC1/2 (HR = 2.91, 95 % CI 1.95-4.34 for twofold increase, p < 0.001) and high initial parasitaemia (HR = 2.23, 95 % CI 1.44-3.45 for tenfold increase, p < 0.001) were associated independently with an increased risk of recrudescence. In western Cambodia, the region with the highest prevalence of artemisinin resistance, there was no evidence for increasing PC1/2 since 2007. Conclusions: Several factors affect PC1/2. As substantial heterogeneity in parasite clearance exists between locations, early detection of artemisinin resistance requires reference PC1/2 data. Studies with frequent parasite count measurements to characterize PC1/2 should be encouraged. In western Cambodia, where PC1/2 values are longest, there is no evidence for recent emergence of higher levels of artemisinin resistance.
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| 2. |
- Adjuik, Martin A., et al.
(författare)
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The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria : a meta-analysis of individual patient data
- 2015
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. Methods: Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites. Results: Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated with a 3.5-fold greater risk of recrudescence by day 28 (adjusted hazard ratio, AHR = 3.51 [95% CI: 2.02-6.12], P < 0.001) compared to FDC, and treatment with loose NFDC-30 was associated with a higher risk of recrudescence at only three sites. Conclusions: There was substantial variation in the total dose of amodiaquine administered in different AS-AQ combination regimens. Fixed dose AS-AQ combinations ensure optimal dosing and provide higher antimalarial treatment efficacy than the loose individual tablets in all age categories.
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| 3. |
- 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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| 4. |
- de Castro Araujo Moreira, Andrea Cristina, et al.
(författare)
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The first Brazilian Field Lab fully dedicated to CO2 MMV experiments : from the start-up to the initial results
- 2014
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Ingår i: 12th International Conference on Greenhouse Gas Control Technologies, GHGT-12. - : Elsevier. ; , s. 6227-6238
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Konferensbidrag (refereegranskat)abstract
- Currently one of the main challenges in CO2 storage research is the development, testing and validation of accurate and efficient Measuring, Monitoring and Verification (MMV) techniques to be deployed at geological sequestration sites that are cost effective yet help minimize risk. This perspective motivated PETROBRAS, the National Oil Major in Brazil, through its R&D investments portfolio to prioritize research projects that would contribute to decreasing the technological gap in the area. The Company's periodic surveys indicated the lack of infrastructure, as well as expertise in CO2 MMV, as two of the most critical issues at the national level. In order to bridge that gap, initial steps were taken in 2010 for the start-up and development of the first CO2 MMV Field Lab in Brazil, fully sponsored by PETROBRAS, with a long term goal of enabling the ranking of the best, most cost-effective MMV technology alternatives to be deployed at commercial large scale CCGS sites scheduled to be installed in the country. In addition to providing basic infrastructure to carry out the CO2 injection and controlled release experiments, the facility was designed for the simultaneous testing of multiple measuring methodologies. Additional benefits of the initiative are the creation of expertise and the acceleration of the know-how in MMV in Brazil, as well as the development of a deeper and more practical knowledge of CO2 dynamics and impacts in a real world, open air scenario. Under the full support of the PETROBRAS R&D Center (CENPES), through its Climate Change Mitigation Technological Program (PROCLIMA), the Brazilian Pilot CO2 MMV Lab was made possible through a joint 4-year research Project, conceived and carried out by PETROBRAS and local academia in Brazil, in close cooperation with international experts. An overview of the Project and the multiple research areas encompassed will be presented, together with the preliminary results of the first CO2 injection campaign, which took place in 2013. (c) 2014 The Authors. Published by Elsevier
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| 5. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 6. |
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| 7. |
- Melo, Clarissa L., et al.
(författare)
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CO2MOVE Project : The New Brazilian Field Lab Fully Dedicated to CO2 MMV Experiments
- 2017
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Ingår i: 13th International Conference on Greenhouse Gas Control Technologies, GHGT-13. - : Elsevier. ; , s. 3699-3715
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Konferensbidrag (refereegranskat)abstract
- After the Ressacada Project experience acquired from 2011 to 2015 when PUCRS, UNESP and other institutions conducted three controlled CO2 release experiments, PETROBRAS, the national oil company that is sponsoring the project, has launched a new challenge to its partners. The company stimulated the implementation of a new Brazilian experimental site where there will be a deepening of studies in geologically more complex conditions and more challenging from a technological point of view. The choice of an area inside PUCRS campus, in Viamao - Rio Grande do Sul state, was motivated by a predominantly clay subsoil and the privileged location of the site in terms of ease logistics and security, which is required for a project of this size that houses high-tech equipment with significant cost. The CO2MOVE project started at 2015 with the subsurface characterization of the site and the assembly and manufacture of an automated system for CO2 and gas tracers with injection capacity for 5 to 50 kg/ day. Based on physical characterization studies and on numerical modeling that is being developed, the site infrastructure will be completed in the next months with the positioning of vertical injection wells, monitoring wells, and other equipment and monitoring mesh. Monitoring tools should be arranged in an area of approximately 100m(2), occupying the entire region surrounding the injection wells. Fieldwork involving CO2 injection and monitoring should have a 60 days duration of which 15 days are for preliminary surveys (pre-injection), 30 days for injection and CO2 monitoring and the last 15 days for post-injection measurements. Following this work, the collected data will be analyzed in the university labs. Similarly to Ressacada Project, this experiment will run measurements of soil CO2 flux with accumulation chambers, CO2 turbulent fluxes with Eddy Covariance, subsurface gases and groundwater monitoring, and resistivity measurements. Other monitoring methods still not tested by the research team will be held as gas tracers monitoring and laser measurements. (C) 2017 The Authors. Published by Elsevier Ltd.
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| 8. |
- Melo, Clarissa L., et al.
(författare)
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Integration results of soil CO2 flux and subsurface gases in the Ressacada Pilot site, Southern Brazil
- 2017
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Ingår i: 13th International Conference on Greenhouse Gas Control Technologies, GHGT-13. - : Elsevier. ; , s. 3793-3804
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Konferensbidrag (refereegranskat)abstract
- The first CO2 monitoring field lab at the Ressacada Farm, in the Southern region of Brazil, started in 2011 and until 2015 offered an excellent opportunity to run controlled CO2 releases experiments in soil and shallow subsurface through vertical injection wells. This paper focus on the presentation and comparison of the results obtained at the last campaign realized at this site in August 2015. The results integrate a time-lapse monitoring experiment of CO2 migration in both saturated and unsaturated sand-rich sediments and soil, using soil CO2 flux measurements and subsurface gas analyses through CO2 concentrations (ppm) and carbon isotope ratios (delta C-13 of CO2). The CO2 flux results in the studied area showed an increase in the flux values according to the increasing of injection rate and along the campaign are directed to the southwest portion of the area. However, even by injecting large amounts of CO2, fluxes are greatly reduced when it rains. The gas analysis also showed an increase in CO2 concentrations according to the increasing of the injection rate mainly in the superficial levels of the monitoring wells (0.5m and 2m depth). The delta C-13 of CO2 found on the 3rd injection day showed the presence of CO2 injected and demonstrate that the sampling methodology with vacutainer vial was effective, since there is no atmospheric contamination. The correlation of isotopic analysis were consistent with the results of concentrations and CO2 fluxes and thus, it is clear that the CO2 breakthrough occurred from the 3rd day of injection, while were obtained the largest CO2 fluxes, the higher gas concentrations in the subsurface, as well as the industrial origin of delta C-13 of CO2.
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| 9. |
- Melo, Clarissa Lovato, et al.
(författare)
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Study of gas tracers for CO2 monitoring
- 2014
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Ingår i: 12th International Conference on Greenhouse Gas Control Technologies, GHGT-12. - : Elsevier. ; , s. 3864-3868
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Konferensbidrag (refereegranskat)abstract
- Gas tracers have been tested libr monitoring and detecting CO, displacement in the underground and eventually leakages to the upper layers in geological storage sites. Commonly used tracers are perfluorocarbons (PFCs) and sulfur hexafluoride (SF6). In Brazil, we are canying out gas tracers studies in laboratory for further application in field test 'facilities. These experiments consist of injecting CO, with perfluorocarbon (perfluoropropane PP and pealuormethylcyclopentane PMCP) at low pressure (ca. 290 psi) in pressurized vessels with different types of sediments and soil samples. After flowing through the sample pores, the tracer is adsorbed into a capillary adsorption tube (CAT) with a specific fiber for perfluorcabon. Then, the tracer is extracted from the CAT through a Thermal Desorption System and subsequently analyzed in a Gas Chromatograph with an Electron Capture Detector (GC ECD). The objective of these experiments is to evaluate the PFCs as a monitoring tool; analyzing the tracer retention times in different sediments, as well as understanding the CATs adsorption capacity and performance. After laboratory tests, field experiments will be conducted in the course of this project. Several experiments of CO2 injection and controlled leaks will be developed in shallow vertical wells at the project site as a continuity of the experiments started at Ressacada Fann Site (Florianopolis, Brazil). The project aim is to understand the flow and dispersion of CO2 in soil and atmosphere simulating an eventual leakage from a geological reservoir using an automated system with a dedicated module for tracers injection into CO2 stream. (C) 2015 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creavativecommons.org/licesses/by-nc-nd/3.0/). Peer-review under responsibility of the Organizing Committee of GLIGT-12
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| 10. |
- Oliva, Andresa, et al.
(författare)
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A comparison of three methods for monitoring CO2 migration in soil and shallow subsurface in the Ressacada Pilot site, Southern Brazil
- 2014
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Ingår i: 12th International Conference on Greenhouse Gas Control Technologies, GHGT-12. - : Elsevier. ; , s. 3992-4002
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Konferensbidrag (refereegranskat)abstract
- In a joint R&D project under the full sponsorship of PETROBRAS, the Brazilian National Oil Company, the first CO2 monitoring field lab was started-up in Brazil in 2011. The site chosen, the Ressacada Farm, in the Southern region of the country, offered an excellent opportunity to run controlled CO2 release experiments in soil and shallow subsurface (< 3 m depth). This paper focuses on the presentation and comparison of the results obtained using electrical imaging, CO2 flux measurements and geochemical analysis of the groundwater to monitor CO2 migration in both saturated and unsaturated sand-rich sediments and soil. In 2013 a controlled release campaign was run, covering an area of approximately 6,300 m(2). Commercial food-grade gaseous carbon dioxide was continuously injected at 3 m depth for 12 days. The average injection rate was 90 g/day, totaling ca. 32kg of gas being released. The low injection rate avoided fracturing of the unconsolidated sediments composing the bulk of the local soil matrix. Monitoring techniques deployed during 30 consecutive days, including background characterization, injection and post-injection periods, were: (1) 3D electrical imaging using a Wenner array, (2) soil CO2 flux measurements using accumulation chambers, (3) water sampling and analysis, (4) 3D (tridimensional) and 4D (time-lapsed) electrical imaging covering depth levels to approximately 10 m below the surface. Water geochemical monitoring consisted of the analyses of several chemical parameters, as well as acidity and electrical conductivity in five multi-level wells (2m; 4m and 6 m depth) installed in the vicinity of the CO2 injection well. Comparison of pre- and post-injection electrical imaging shows changes in resistivity values consistent with CO(2)migration pathways. A pronounced increase in resistivity values occurred, from 1,500 ohm. m to 2,000 ohm. m, in the vicinity of the injection well. The accumulation chamber assessment show significant changes in the CO2 flux during the release experiment: maximum values detected were ca. 270 mmol/m(2)/s(during injection) as compared to background values of c.a. 34mmol/m(2)/s. The pH showed variations after CO2 injection in two monitoring wells at 2m, 4m and 6m depth. After the CO2 injection ceased, the lowest pH measured was 4.1, which represents a decrease of 0.5 relative to the background values. Slight variations in the oxidation-reduction potential (Eh) were observed near the CO2 injection well. There was a decreasing trend of this potential, especially in a monitoring well at 6m depth, ranging from 308mV to 229mV, between the background and the injection scenarios. Ppb level increments were detected in the measurements carried out for the major cations (Ca, Mg, Na, and P) and trace elements (Ag, Al, As, B, Ba, Cd, Pb, Cu, Cr, Ni, Mn, S, V, and Zn). Electrical conductivity and alkalinity, however, remained constant throughout the experiment, with values around 40 mu S.cm(-1) and 2.5 mgCaCO(3).L-1, respectively. The response to CO2 injection was not uniformly observed by the different methods deployed on site. The highest percentage change in resistivity values near the injection well occurred 5 days after the injection had started. However the highest percentage changes in the CO2 flux values occurred 9 days after the injection, 4 days after the observed changes in resistivity values. This delay is probably due to the migration time of the gas from 0.5m depth to the surface. (C) 2014 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). Peer-review under responsibility of the Organizing Committee of GHGT-12
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