| 1. |
- Mansoor, Rashid, et al.
(författare)
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Haematological consequences of acute uncomplicated falciparum malaria : a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data
- 2022
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Ingår i: BMC Medicine. - : Springer Nature. - 1741-7015. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPlasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia.MethodsIndividual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall >= 25% at day 3 and day 7.ResultsA total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to >= 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39-3.05], p < 0.001).ConclusionsIn patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery.
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| 2. |
- Dahal, Prabin, et al.
(författare)
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Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy : an individual participant data meta-analysis
- 2022
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Ingår i: Malaria Journal. - : Springer Nature. - 1475-2875 .- 1475-2875. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- Background: The duration of trial follow-up affects the ability to detect recrudescent infections following anti-malarial treatment. The aim of this study was to explore the proportions of recrudescent parasitaemia as ascribed by genotyping captured at various follow-up time-points in treatment efficacy trials for uncomplicated Plasmodium falciparum malaria.Methods: Individual patient data from 83 anti-malarial efficacy studies collated in the WorldWide Antimalarial Resistance Network (WWARN) repository with at least 28 days follow-up were available. The temporal and cumulative distributions of recrudescence were characterized using a Cox regression model with shared frailty on study-sites. Fractional polynomials were used to capture non-linear instantaneous hazard. The area under the density curve (AUC) of the constructed distribution was used to estimate the optimal follow-up period for capturing a P. falciparum malaria recrudescence. Simulation studies were conducted based on the constructed distributions to quantify the absolute overestimation in efficacy due to sub-optimal follow-up.Results: Overall, 3703 recurrent infections were detected in 60 studies conducted in Africa (15,512 children aged < 5 years) and 23 studies conducted in Asia and South America (5272 patients of all ages). Using molecular genotyping, 519 (14.0%) recurrences were ascribed as recrudescent infections. A 28 day artemether-lumefantrine (AL) efficacy trial would not have detected 58% [95% confidence interval (CI) 47-74%] of recrudescences in African children and 32% [95% CI 15-45%] in patients of all ages in Asia/South America. The corresponding estimate following a 42 day dihydroartemisinin-piperaquine (DP) efficacy trial in Africa was 47% [95% CI 19-90%] in children under 5 years old treated with > 48 mg/kg total piperaquine (PIP) dose and 9% [95% CI 0-22%] in those treated with <= 48 mg/kg PIP dose. In absolute terms, the simulation study found that trials limited to 28 days follow-up following AL underestimated the risk of recrudescence by a median of 2.8 percentage points compared to day 63 estimates and those limited to 42 days following DP underestimated the risk of recrudescence by a median of 2.0 percentage points compared to day 42 estimates. The analysis was limited by few clinical trials following patients for longer than 42 days (9 out of 83 trials) and the imprecision of PCR genotyping which overcalls recrudescence in areas of higher transmission biasing the later distribution.Conclusions: Restricting follow-up of clinical efficacy trials to day 28 for AL and day 42 for DP will miss a proportion of late recrudescent treatment failures but will have a modest impact in derived efficacy. The results highlight that as genotyping methods improve consideration should be given for trials with longer duration of follow-up to detect early indications of emerging drug resistance.
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| 3. |
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| 4. |
- Schwamb, Megan E., et al.
(författare)
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Tuning the Legacy Survey of Space and Time (LSST) Observing Strategy for Solar System Science
- 2023
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Ingår i: Astrophysical Journal Supplement Series. - : Iop Publishing Ltd. - 0067-0049 .- 1538-4365. ; 266:2
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Tidskriftsartikel (refereegranskat)abstract
- The Vera C. Rubin Observatory is expected to start the Legacy Survey of Space and Time (LSST) in early to mid-2025. This multiband wide-field synoptic survey will transform our view of the solar system, with the discovery and monitoring of over five million small bodies. The final survey strategy chosen for LSST has direct implications on the discoverability and characterization of solar system minor planets and passing interstellar objects. Creating an inventory of the solar system is one of the four main LSST science drivers. The LSST observing cadence is a complex optimization problem that must balance the priorities and needs of all the key LSST science areas. To design the best LSST survey strategy, a series of operation simulations using the Rubin Observatory scheduler have been generated to explore the various options for tuning observing parameters and prioritizations. We explore the impact of the various simulated LSST observing strategies on studying the solar system's small body reservoirs. We examine what are the best observing scenarios and review what are the important considerations for maximizing LSST solar system science. In general, most of the LSST cadence simulations produce +/- 5% or less variations in our chosen key metrics, but a subset of the simulations significantly hinder science returns with much larger losses in the discovery and light-curve metrics.
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| 5. |
- Wynberg, Elke, et al.
(författare)
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Variability in white blood cell count during uncomplicated malaria and implications for parasite density estimation : a WorldWide Antimalarial Resistance Network individual patient data meta-analysis
- 2023
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Ingår i: Malaria Journal. - : Springer Nature. - 1475-2875 .- 1475-2875. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: The World Health Organization (WHO) recommends that when peripheral malarial parasitaemia is quantified by thick film microscopy, an actual white blood cell (WBC) count from a concurrently collected blood sample is used in calculations. However, in resource-limited settings an assumed WBC count is often used instead. The aim of this study was to describe the variability in WBC count during acute uncomplicated malaria, and estimate the impact of using an assumed value of WBC on estimates of parasite density and clearance.Methods: Uncomplicated malaria drug efficacy studies that measured WBC count were selected from the WorldWide Antimalarial Resistance Network data repository for an individual patient data meta-analysis of WBC counts. Regression models with random intercepts for study-site were used to assess WBC count variability at presentation and during follow-up. Inflation factors for parasitaemia density, and clearance estimates were calculated for methods using assumed WBC counts (8000 cells/mu L and age-stratified values) using estimates derived from the measured WBC value as reference.Results: Eighty-four studies enrolling 27,656 patients with clinically uncomplicated malaria were included. Geometric mean WBC counts (x 1000 cells/mu L) in age groups < 1, 1-4, 5-14 and >= 15 years were 10.5, 8.3, 7.1, 5.7 and 7.5, 7.0, 6.5, 6.0 for individuals with falciparum (n = 24,978) and vivax (n = 2678) malaria, respectively. At presentation, higher WBC counts were seen among patients with higher parasitaemia, severe anaemia and, for individuals with vivax malaria, in regions with shorter regional relapse periodicity. Among falciparum malaria patients, using an assumed WBC count of 8000 cells/mu L resulted in parasite density underestimation by a median (IQR) of 26% (4-41%) in infants < 1 year old but an overestimation by 50% (16-91%) in adults aged = 15 years. Use of age-stratified assumed WBC values removed systematic bias but did not improve precision of parasitaemia estimation. Imprecision of parasite clearance estimates was only affected by the within-patient WBC variability over time, and remained < 10% for 79% of patients.Conclusions: Using an assumed WBC value for parasite density estimation from a thick smear may lead to underdiagnosis of hyperparasitaemia and could adversely affect clinical management; but does not result in clinically consequential inaccuracies in the estimation of the prevalence of prolonged parasite clearance and artemisinin resistance.
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| 6. |
- Dorsey, E. Ray, et al.
(författare)
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Deep Phenotyping of Parkinson's Disease
- 2020
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Ingår i: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 10:3, s. 855-873
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Forskningsöversikt (refereegranskat)abstract
- Phenotype is the set of observable traits of an organism or condition. While advances in genetics, imaging, and molecular biology have improved our understanding of the underlying biology of Parkinson's disease (PD), clinical pheno-typing of PD still relies primarily on history and physical examination. These subjective, episodic, categorical assessments are valuable for diagnosis and care but have left gaps in our understanding of the PD phenotype. Sensors can provide objective, continuous, real-world data about the PD clinical phenotype, increase our knowledge of its pathology, enhance evaluation of therapies, and ultimately, improve patient care. In this paper, we explore the concept of deep phenotyping-the comprehensive assessment of a condition using multiple clinical, biological, genetic, imaging, and sensor-based tools-for PD. We discuss the rationale for, outline current approaches to, identify benefits and limitations of, and consider future directions for deep clinical phenotyping.
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| 8. |
- Furén, Robert, Industridoktorand, et al.
(författare)
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Concentration, distribution, and fractionation of metals in the filter material of 29 bioretention facilities: a field study
- 2023
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Ingår i: Environmental Science. - : Royal Society of Chemistry. - 2053-1400 .- 2053-1419. ; 9:12, s. 3158-3173
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Tidskriftsartikel (refereegranskat)abstract
- Pollutant loads stemming from anthropogenic activities conveyed in urban stormwater runoff contribute to the impairment of downstream water bodies. Cities and municipalities are increasingly turning toward green infrastructure stormwater control measures to treat pollutants at the source of runoff. One example of these technologies is bioretention, which is commonly applied for stormwater treatment in urban areas due to its demonstrated effectiveness in removing various pollutants from water, including sediment, nutrients (e.g., N and P), and metals. As metals are mainly removed by filtration or adsorption to soil particles, the filter media is important for metal removal in bioretention. However, the capacity to remove metals through adsorption by bioretention media is finite; thus, the media may need to be replaced and disposed of after maintenance or at the end of its operational lifespan. Pollutant accumulation in bioretention media has the potential to approach toxicity thresholds, which may introduce complexities for safe handling and disposal. To fully capture the potential challenges associated with metals accumulation in media over time, it is important to understand the accumulation processes and mobility of metals in bioretention facilities as they age. Although several studies have investigated metal accumulation and distribution in bioretention media, few have assessed metal mobility by fractionation using sequential extraction methods in older (i.e., >7 years) facilities. In November 2019, we conducted a comprehensive field study of older facilities in Ohio, Michigan, and Kentucky (USA) to improve the understanding of the accumulation processes and metal mobility in bioretention. In this study, concentrations of several metals (i.e., Cr, Cu, Ni, Pb, and Zn) were analyzed in samples of filter material from 29 bioretention sites in operation for 7–16 years. Except for Cd, all metals were found in all samples. Metals accumulation was clear with highest concentrations found in the top (0–5 cm) layer of the filter material, attributable to the filtration of particles percolating through the media profile. Lower concentrations were observed in deeper (i.e., >10 cm) layers of the bioretention media. The fractionation showed that the metals of interest were present at high levels with a risk of leaching over time, among which Cd, Zn, and Pb were suggested to be mobile from the filter material during precipitation. Thus, there is a potential risk of leakage from filter material or sediment removed from biofilters, e.g., during maintenance and disposal. The results of principal component analysis indicated specifically correlations between metal concentrations and the filter material soil texture including the organic matter content. These results contribute to improved design and operation and suggest regular maintenance to reduce long-term risks associated with the accumulation of metals in bioretention and similar urban stormwater treatment facilities. Since most metals are trapped in the top layer of the filter it may be enough to remove only the top layer. However, metal fractionation should be considered when handling the material.
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| 9. |
- Furén, Robert, Industridoktorand, et al.
(författare)
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Occurrence, concentration, and distribution of 38 organic micropollutants in the filter material of 12 stormwater bioretention facilities
- 2022
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 846
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Tidskriftsartikel (refereegranskat)abstract
- The increased use of bioretention facilities as a low impact development measure for treating stormwater runoff underscores the need to further understand their long-term function. Eventually, bioretention filter media must be (partly) replaced and disposed of at the end of its functional lifespan. While there are several studies of metal accumulation and distributions in bioretention media, less is known about organic pollutant pathways and accumulation in these filters. The present study considers the occurrence and accumulation of 16 polycyclic aromatic hydrocarbons, 7 polychlorinated biphenyls, 13 phthalates, and two alkylphenols throughout 12 older bioretention facilities (7–13 years old) used for stormwater treatment in Michigan and Ohio, USA. These pollutant groups appear to behave similarly, with greater instances of detection and higher concentrations in the upper media layers which decrease with increased depth from the surface. The patterns of detection and concentration in the filter material may be explained by characteristics of the pollutants, such as molecular structures and solubility that affect the removal of the organic pollutants by the filter material. There is also a large variation in concentration magnitudes between the bioretention sites, most likely due to differences in pollutant sources, contributing catchment size and/or land uses.
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| 10. |
- Lange, Katharina, et al.
(författare)
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Abundance, distribution, and composition of microplastics in the filter media of nine aged stormwater bioretention systems
- 2023
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Ingår i: Chemosphere. - : Elsevier Ltd. - 0045-6535 .- 1879-1298. ; 320
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Tidskriftsartikel (refereegranskat)abstract
- Bioretention systems are designed for quality treatment of stormwater. Particulate contaminants are commonly treated efficiently and accumulate mainly in the surface layer of the bioretention filter material. However, concerns exist that microplastic particles may not show equal accumulation behavior as other sediment particles. So far only two field and two laboratory studies are available on the fate of microplastics in few relatively newly built bioretention systems. Therefore, this study investigated the abundance and distribution of microplastics in nine 7–12 years old stormwater bioretention systems. It was found that microplastics generally accumulate on the surface of bioretention systems. Microplastic median particle concentrations decreased significantly from the surface layer (0–5 cm) of the filter material to the 10–15 cm depth layer from 448 to 136 particles/100 g, respectively. The distance to the inlet did not significantly affect the surface accumulation of microplastic particles, suggesting modest spatial variability in microplastics accumulation in older bioretention systems. Further, this study investigated the polymer composition in bioretention systems. It was shown that PP, EVA, PS and EPDM rubber are the most abundant polymer types in bioretention systems. Also, it was found that large percentages of microplastic particles are black particles (median percentage of black particles: 39%) which were found in 28 of the 33 investigated samples. This underlines the importance of including black particles in microplastic studies on stormwater, which has been overlooked in most previous studies.
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