| 1. |
- Dahal, Prabin, et al.
(författare)
-
Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy : an individual participant data meta-analysis
- 2022
-
Ingår i: Malaria Journal. - : Springer Nature. - 1475-2875. ; 21
-
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.
|
|
| 2. |
- Flechard, Chris R., et al.
(författare)
-
Carbon-nitrogen interactions in European forests and semi-natural vegetation - Part 1: Fluxes and budgets of carbon, nitrogen and greenhouse gases from ecosystem monitoring and modelling
- 2020
-
Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 17:6, s. 1583-1620
-
Tidskriftsartikel (refereegranskat)abstract
- The impact of atmospheric reactive nitrogen (N-r) deposition on carbon (C) sequestration in soils and biomass of unfertilized, natural, semi-natural and forest ecosystems has been much debated. Many previous results of this dC/dN response were based on changes in carbon stocks from periodical soil and ecosystem inventories, associated with estimates of N-r deposition obtained from large-scale chemical transport models. This study and a companion paper (Flechard et al., 2020) strive to reduce uncertainties of N effects on C sequestration by linking multi-annual gross and net ecosystem productivity estimates from 40 eddy covariance flux towers across Europe to local measurement-based estimates of dry and wet N-r deposition from a dedicated collocated monitoring network. To identify possible ecological drivers and processes affecting the interplay between C and N-r inputs and losses, these data were also combined with in situ flux measurements of NO, N2O and CH4 fluxes; soil NO3- leaching sampling; and results of soil incubation experiments for N and greenhouse gas (GHG) emissions, as well as surveys of available data from online databases and from the literature, together with forest ecosystem (BAS-FOR) modelling. Multi-year averages of net ecosystem productivity (NEP) in forests ranged from -70 to 826 gCm(-2) yr(-1) at total wet + dry inorganic N-r deposition rates (N-dep) of 0.3 to 4.3 gNm(-2) yr(-1) and from -4 to 361 g Cm-2 yr(-1) at N-dep rates of 0.1 to 3.1 gNm(-2) yr(-1) in short semi-natural vegetation (moorlands, wetlands and unfertilized extensively managed grasslands). The GHG budgets of the forests were strongly dominated by CO2 exchange, while CH4 and N2O exchange comprised a larger proportion of the GHG balance in short semi-natural vegetation. Uncertainties in elemental budgets were much larger for nitrogen than carbon, especially at sites with elevated N-dep where N-r leaching losses were also very large, and compounded by the lack of reliable data on organic nitrogen and N-2 losses by denitrification. Nitrogen losses in the form of NO, N2O and especially NO3- were on average 27%(range 6 %-54 %) of N-dep at sites with N-dep < 1 gNm(-2) yr(-1) versus 65% (range 35 %-85 %) for N-dep > 3 gNm(-2) yr(-1). Such large levels of N-r loss likely indicate that different stages of N saturation occurred at a number of sites. The joint analysis of the C and N budgets provided further hints that N saturation could be detected in altered patterns of forest growth. Net ecosystem productivity increased with N-r deposition up to 2-2.5 gNm(-2) yr(-1), with large scatter associated with a wide range in carbon sequestration efficiency (CSE, defined as the NEP/GPP ratio). At elevated N-dep levels (> 2.5 gNm(-2) yr(-1)), where inorganic N-r losses were also increasingly large, NEP levelled off and then decreased. The apparent increase in NEP at low to intermediate N-dep levels was partly the result of geographical cross-correlations between N-dep and climate, indicating that the actual mean dC/dN response at individual sites was significantly lower than would be suggested by a simple, straightforward regression of NEP vs. N-dep.
|
|
| 3. |
- Heiskanen, Jouni, et al.
(författare)
-
The Integrated Carbon Observation System in Europe
- 2022
-
Ingår i: Bulletin of the American Meteorological Society. - 0003-0007. ; 103:3, s. 855-872
-
Tidskriftsartikel (refereegranskat)abstract
- Since 1750, land-use change and fossil fuel combustion has led to a 46% increase in the atmospheric carbon dioxide (CO2) concentrations, causing global warming with substantial societal consequences. The Paris Agreement aims to limit global temperature increases to well below 2C above preindustrial levels. Increasing levels of CO2 and other greenhouse gases (GHGs), such as methane (CH4) and nitrous oxide (N2O), in the atmosphere are the primary cause of climate change. Approximately half of the carbon emissions to the atmosphere are sequestered by ocean and land sinks, leading to ocean acidification but also slowing the rate of global warming. However, there are significant uncertainties in the future global warming scenarios due to uncertainties in the size, nature, and stability of these sinks. Quantifying and monitoring the size and timing of natural sinks and the impact of climate change on ecosystems are important information to guide policy-makers' decisions and strategies on reductions in emissions. Continuous, long-term observations are required to quantify GHG emissions, sinks, and their impacts on Earth systems. The Integrated Carbon Observation System (ICOS) was designed as the European in situ observation and information system to support science and society in their efforts to mitigate climate change. It provides standardized and open data currently from over 140 measurement stations across 12 European countries. The stations observe GHG concentrations in the atmosphere and carbon and GHG fluxes between the atmosphere, land surface, and the oceans. This article describes how ICOS fulfills its mission to harmonize these observations, ensure the related long-term financial commitments, provide easy access to well-documented and reproducible high-quality data and related protocols and tools for scientific studies, and deliver information and GHG-related products to stakeholders in society and policy.
|
|
| 4. |
- Papale, Dario, et al.
(författare)
-
Standards and Open Access are the ICOS Pillars Reply to "Comments on 'The Integrated Carbon Observation System in Europe'"
- 2023
-
Ingår i: Bulletin of the American Meteorological Society. - 0003-0007. ; 104:12, s. 953-955
-
Tidskriftsartikel (refereegranskat)abstract
- In his comment (Kowalski 2023) on our recent publication (Heiskanen et al. 2022) where we present the Integrated Carbon Observation System (ICOS) research infrastructure, Andrew Kowalski introduces three important and, in our opinion, different potential issues in the definition, collection, and availability of field measurements made by the ICOS network, and he proposes possible solutions to these issues.
|
|
