| 1. |
- Niemi, MEK, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 2. |
- Aamodt, K., et al.
(författare)
-
The ALICE experiment at the CERN LHC
- 2008
-
Ingår i: Journal of Instrumentation. - 1748-0221. ; 3:S08002
-
Forskningsöversikt (refereegranskat)abstract
- ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries, Its overall dimensions are 16 x 16 x 26 m(3) with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.
|
|
| 3. |
- Kanai, M, et al.
(författare)
-
- 2023
-
swepub:Mat__t
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Bousquet, J., et al.
(författare)
-
Building Bridges for Innovation in Ageing : Synergies between Action Groups of the EIP on AHA
- 2017
-
Ingår i: The Journal of Nutrition, Health & Aging. - : Springer Nature. - 1279-7707 .- 1760-4788. ; 21:1, s. 92-104
-
Tidskriftsartikel (refereegranskat)abstract
- The Strategic Implementation Plan of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) proposed six Action Groups. After almost three years of activity, many achievements have been obtained through commitments or collaborative work of the Action Groups. However, they have often worked in silos and, consequently, synergies between Action Groups have been proposed to strengthen the triple win of the EIP on AHA. The paper presents the methodology and current status of the Task Force on EIP on AHA synergies. Synergies are in line with the Action Groups' new Renovated Action Plan (2016-2018) to ensure that their future objectives are coherent and fully connected. The outcomes and impact of synergies are using the Monitoring and Assessment Framework for the EIP on AHA (MAFEIP). Eight proposals for synergies have been approved by the Task Force: Five cross-cutting synergies which can be used for all current and future synergies as they consider overarching domains (appropriate polypharmacy, citizen empowerment, teaching and coaching on AHA, deployment of synergies to EU regions, Responsible Research and Innovation), and three cross-cutting synergies focussing on current Action Group activities (falls, frailty, integrated care and chronic respiratory diseases).
|
|
| 8. |
|
|
| 9. |
- Sabatini, F. M., et al.
(författare)
-
sPlotOpen - An environmentally balanced, open-access, global dataset of vegetation plots
- 2021
-
Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238.
-
Tidskriftsartikel (refereegranskat)abstract
- Motivation Assessing biodiversity status and trends in plant communities is critical for understanding, quantifying and predicting the effects of global change on ecosystems. Vegetation plots record the occurrence or abundance of all plant species co-occurring within delimited local areas. This allows species absences to be inferred, information seldom provided by existing global plant datasets. Although many vegetation plots have been recorded, most are not available to the global research community. A recent initiative, called 'sPlot', compiled the first global vegetation plot database, and continues to grow and curate it. The sPlot database, however, is extremely unbalanced spatially and environmentally, and is not open-access. Here, we address both these issues by (a) resampling the vegetation plots using several environmental variables as sampling strata and (b) securing permission from data holders of 105 local-to-regional datasets to openly release data. We thus present sPlotOpen, the largest open-access dataset of vegetation plots ever released. sPlotOpen can be used to explore global diversity at the plant community level, as ground truth data in remote sensing applications, or as a baseline for biodiversity monitoring. Main types of variable contained Vegetation plots (n = 95,104) recording cover or abundance of naturally co-occurring vascular plant species within delimited areas. sPlotOpen contains three partially overlapping resampled datasets (c. 50,000 plots each), to be used as replicates in global analyses. Besides geographical location, date, plot size, biome, elevation, slope, aspect, vegetation type, naturalness, coverage of various vegetation layers, and source dataset, plot-level data also include community-weighted means and variances of 18 plant functional traits from the TRY Plant Trait Database. Spatial location and grain Global, 0.01-40,000 m(2). Time period and grain 1888-2015, recording dates. Major taxa and level of measurement 42,677 vascular plant taxa, plot-level records. Software format Three main matrices (.csv), relationally linked.
|
|
| 10. |
- Kattge, Jens, et al.
(författare)
-
TRY plant trait database - enhanced coverage and open access
- 2020
-
Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
-
Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
|
|
| 11. |
- Cung, T. -T., et al.
(författare)
-
Cyclosporine before PCI in Patients with Acute Myocardial Infarction
- 2015
-
Ingår i: New England Journal of Medicine. - 0028-4793. ; 373:11, s. 1021-1031
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling. METHODS In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume. RESULTS A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval, 0.78 to 1.39; P = 0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups. CONCLUSIONS In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.)
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Falster, Daniel, et al.
(författare)
-
AusTraits, a curated plant trait database for the Australian flora
- 2021
-
Ingår i: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
- Mansoor, Rashid, et al.
(författare)
-
Haematological consequences of acute uncomplicated falciparum malaria : a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data
- 2022
-
Ingår i: BMC Medicine. - : Springer Nature. - 1741-7015. ; 20:1
-
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.
|
|
| 19. |
- Venkatesan, M, et al.
(författare)
-
Erratum
- 2019
-
Ingår i: The American journal of tropical medicine and hygiene. - : American Society of Tropical Medicine and Hygiene. - 1476-1645 .- 0002-9637. ; 100:3, s. 766-766
-
Tidskriftsartikel (refereegranskat)
|
|
| 20. |
- Wade, C. M., et al.
(författare)
-
Genome Sequence, Comparative Analysis, and Population Genetics of the Domestic Horse
- 2009
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 326:5954, s. 865-867
-
Tidskriftsartikel (refereegranskat)abstract
- We report a high-quality draft sequence of the genome of the horse ( Equus caballus). The genome is relatively repetitive but has little segmental duplication. Chromosomes appear to have undergone few historical rearrangements: 53% of equine chromosomes show conserved synteny to a single human chromosome. Equine chromosome 11 is shown to have an evolutionary new centromere devoid of centromeric satellite DNA, suggesting that centromeric function may arise before satellite repeat accumulation. Linkage disequilibrium, showing the influences of early domestication of large herds of female horses, is intermediate in length between dog and human, and there is long-range haplotype sharing among breeds.
|
|
| 21. |
|
|
| 22. |
- Adjuik, Martin A., et al.
(författare)
-
The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria : a meta-analysis of individual patient data
- 2015
-
Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 13
-
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.
|
|
| 23. |
- Dahal, Prabin, et al.
(författare)
-
Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria : a WorldWide Antimalarial Resistance Network individual participant data meta-analysis
- 2019
-
Ingår i: Malaria Journal. - : BMC. - 1475-2875. ; 18
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections.Methods: Antimalarial studies typically report the risk of recrudescence derived using the Kaplan-Meier (K-M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K-M method (1 minus K-M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K-M curves was assessed using the log-rank test, and the equality of CIFs using Gray's k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray's sub-distributional hazard model.Results: Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K-M approach was 0.04% (interquartile range (IQR): 0.00-0.27%, Range: 0.00-3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson's correlation coefficient (rho): 0.38, 95% Confidence Interval (CI) 0.30-0.46] or new infection [rho: 0.43; 95% CI 0.35-0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold for withdrawing antimalarials) when the K-M method was used, but remained below 10% when using the CIF approach, but the 95% confidence interval included this threshold.Conclusions: The 1 minus K-M method resulted in a marginal overestimation of recrudescence that became increasingly pronounced as antimalarial efficacy declined, particularly when the observed proportion of new infection was high. The CIF approach provides an alternative approach for derivation of failure estimates in antimalarial trials, particularly in high transmission settings.
|
|
| 24. |
- 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.
|
|
| 25. |
|
|
| 26. |
- Denoyes-Rothan, B, et al.
(författare)
-
Inheritance of resistance to Colletotrichum acutatum in Fragaria x ananassa
- 2005
-
Ingår i: Phytopathology. - : AMER PHYTOPATHOLOGICAL SOC. - 0031-949X .- 1943-7684. ; 95:4, s. 405-412
-
Tidskriftsartikel (refereegranskat)abstract
- Anthracnose, caused by Colletotrichum acutatum, is a major disease of the octoploid cultivated strawberry, Fragaria x ananassa. The inheritance of high and intermediate level plant resistances to C. acutatum, pathogenicity group 2, was investigated in an 8 x 8 factorial design. A single dominant gene (Rca2) controlled the high-level resistance, although minor genes may also contribute to resistance in cultivars such as Belrubi. The intermediate level of resistance was quantitative and controlled by minor genes. Analysis of 26 genotypes and cultivars from Fragaria spp. showed that the dominant gene was not rare in the germ plasm of E x ananassa and that anthracnose resistance was also present in other species of Fragaria. These findings have important implications for anthracnose resistance breeding.
|
|
| 27. |
- Galle, Jan-Christoph, et al.
(författare)
-
An observational cohort study of extended dosing (once every 2 weeks or once monthly) regimens with darbepoetin alfa in patients with chronic kidney disease not on dialysis: the EXTEND study.
- 2012
-
Ingår i: Nephrology, dialysis, transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 27:6, s. 2303-2311
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Darbepoetin alfa (DA) has been shown to be an effective treatment of anaemia in patients with chronic kidney disease (CKD) not on dialysis (NoD). EXTEND is an observational study assessing the effectiveness of DA administered once biweekly (Q2W) or monthly (QM) in a general CKD-NoD population.METHODS: Adult CKD-NoD patients starting DA Q2W/QM treatment in June 2006 or later were eligible. Retrospective and/or prospective data including haemoglobin levels and erythropoiesis-stimulating agent (ESA) dosing were collected for 6 months before and 12 months after DA initiation. Mean Hb levels were calculated every 3 months, and ESA dose was converted to a geometric mean weekly DA equivalent dose and summarized monthly.RESULTS: Data from 4278 patients showed that patients receiving ESA treatment before DA Q2W/QM initiation had a mean (95% confidence interval) Hb level of 11.9 g/dL (11.8-12.0 g/dL) at initiation and 11.6 g/dL (11.6-11.7 g/dL) at Months 10-12, with mean ESA dose of 22 μg/week (21-23 μg/week) prior to initiation, 16 μg/week (15-16 μg/week) at initiation and 16 μg/week (15-16 μg/week) at Month 12. In ESA-naive patients, Hb levels increased from 10.3 g/dL (10.2-10.3 g/dL) at initiation to 11.7 g/dL at Months 4-6 and were maintained at a mean level of 11.7 g/dL (11.7-11.8 g/dL) at Months 10-12, with mean ESA dose of 16 μg/week (16-17 μg/week) at initiation and 16 μg/week (16-17 μg/week) at Month 12. In the 85% of patients receiving DA at extended intervals (Q2W or less frequently) at Month 12, 12 patients (0.3%) experienced DA-related adverse reactions.CONCLUSION: DA Q2W/QM was an effective treatment of anaemia in the general CKD-NoD patient population and a dose increase was not required in patients switching from a previous ESA regimen.
|
|
| 28. |
- Galle, J. C., et al.
(författare)
-
Outcomes in patients with chronic kidney disease not on dialysis receiving extended dosing regimens of darbepoetin alfa: long-term results of the EXTEND observational cohort study
- 2016
-
Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 31:12, s. 2073-2085
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Extended dosing of the erythropoiesis-stimulating agent (ESA) darbepoetin alfa (DA) once biweekly or monthly reduces anaemia treatment burden. This observational study assessed outcomes and dosing patterns in patients with chronic kidney disease not on dialysis (CKD-NoD) commencing extended dosing of DA. Methods. Adult CKD-NoD patients starting extended dosing of DA in Europe or Australia in June 2006 or later were followed up until December 2012. Outcomes included haemoglobin (Hb) concentration, ESA dosing, mortality rates and receipt of dialysis and renal transplantation. Subgroup analyses were conducted for selected outcomes. Results. Of 6035 enrolled subjects, 5723 (94.8%) met analysis criteria; 1795 (29.7%) received dialysis and 238 (3.9%) underwent renal transplantation. Mean (standard deviation) Hb concentration at commencement of extended dosing was 11.0 (1.5) g/dL. Mean [95% confidence interval (CI)] Hb 12 months after commencement of extended dosing (primary outcome) was 11.6 g/dL (11.5, 11.6) overall and was similar across countries, with no differences between subjects previously treated with an ESA versus ESA-naive subjects, subjects with versus without prior renal transplant or diabetics versus non-diabetics. Weekly ESA dose gradually decreased following commencement of extended DA dosing and was similar across subgroups. The decrease in weekly DA dose was accompanied by an increase in the proportion of patients receiving iron therapy. Hb concentrations declined following changes in ESA labels and treatment guidelines. The mortality rate (95% CI) was 7.06 (6.68, 7.46) deaths per 100 years of follow-up. Subjects alive at study end had stable Hb concentrations in the preceding year, while those who died had lower and declining Hb concentrations in their last year. Conclusions. Long-term, extended dosing of DA maintained Hb concentrations in patients already treated with an ESA and corrected and maintained Hb in ESA-naive patients.
|
|
| 29. |
- Grasselli, Giacomo, et al.
(författare)
-
ESICM guidelines on acute respiratory distress syndrome : definition, phenotyping and respiratory support strategies
- 2023
-
Ingår i: Intensive Care Medicine. - : Springer Nature. - 0342-4642 .- 1432-1238. ; 49, s. 727-759
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.
|
|
| 30. |
- Guérin, C, et al.
(författare)
-
A prospective international observational prevalence study on prone positioning of ARDS patients : the APRONET (ARDS Prone Position Network) study
- 2018
-
Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 44:1, s. 22-37
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: While prone positioning (PP) has been shown to improve patient survival in moderate to severe acute respiratory distress syndrome (ARDS) patients, the rate of application of PP in clinical practice still appears low.AIM: This study aimed to determine the prevalence of use of PP in ARDS patients (primary endpoint), the physiological effects of PP, and the reasons for not using it (secondary endpoints).METHODS: The APRONET study was a prospective international 1-day prevalence study performed four times in April, July, and October 2016 and January 2017. On each study day, investigators in each ICU had to screen every patient. For patients with ARDS, use of PP, gas exchange, ventilator settings and plateau pressure (Pplat) were recorded before and at the end of the PP session. Complications of PP and reasons for not using PP were also documented. Values are presented as median (1st-3rd quartiles).RESULTS: Over the study period, 6723 patients were screened in 141 ICUs from 20 countries (77% of the ICUs were European), of whom 735 had ARDS and were analyzed. Overall 101 ARDS patients had at least one session of PP (13.7%), with no differences among the 4 study days. The rate of PP use was 5.9% (11/187), 10.3% (41/399) and 32.9% (49/149) in mild, moderate and severe ARDS, respectively (P = 0.0001). The duration of the first PP session was 18 (16-23) hours. Measured with the patient in the supine position before and at the end of the first PP session, PaO2/FIO2 increased from 101 (76-136) to 171 (118-220) mmHg (P = 0.0001) driving pressure decreased from 14 [11-17] to 13 [10-16] cmH2O (P = 0.001), and Pplat decreased from 26 [23-29] to 25 [23-28] cmH2O (P = 0.04). The most prevalent reason for not using PP (64.3%) was that hypoxemia was not considered sufficiently severe. Complications were reported in 12 patients (11.9%) in whom PP was used (pressure sores in five, hypoxemia in two, endotracheal tube-related in two ocular in two, and a transient increase in intracranial pressure in one).CONCLUSIONS: In conclusion, this prospective international prevalence study found that PP was used in 32.9% of patients with severe ARDS, and was associated with low complication rates, significant increase in oxygenation and a significant decrease in driving pressure.
|
|
| 31. |
|
|
| 32. |
- Sloot, Frea, et al.
(författare)
-
Inventory of current EU paediatric vision and hearing screening programmes
- 2015
-
Ingår i: Journal of Medical Screening. - : SAGE Publications. - 0969-1413 .- 1475-5793. ; 22:2, s. 55-64
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the diversity in paediatric vision and hearing screening programmes in Europe. Methods: Themes for comparison of screening programmes derived from literature were used to compile three questionnaires on vision, hearing, and public health screening. Tests used, professions involved, age, and frequency of testing seem to influence sensitivity, specificity, and costs most. Questionnaires were sent to ophthalmologists, orthoptists, otolaryngologists, and audiologists involved in paediatric screening in all EU full-member, candidate, and associate states. Answers were cross-checked. Results: Thirty-nine countries participated; 35 have a vision screening programme, 33 a nation-wide neonatal hearing screening programme. Visual acuity (VA) is measured in 35 countries, in 71% of these more than once. First measurement of VA varies from three to seven years of age, but is usually before age five. At age three and four, picture charts, including Lea Hyvarinen, are used most; in children over four, Tumbling-E and Snellen. As first hearing screening test, otoacoustic emission is used most in healthy neonates, and auditory brainstem response in premature newborns. The majority of hearing testing programmes are staged; children are referred after 1–4 abnormal tests. Vision screening is performed mostly by paediatricians, ophthalmologists, or nurses. Funding is mostly by health insurance or state. Coverage was reported as >95% in half of countries, but reporting was often not first-hand. Conclusion: Largest differences were found in VA charts used (12), professions involved in vision screening (10), number of hearing screening tests before referral (1–4), and funding sources (8).
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
- Blyth, Colette, et al.
(författare)
-
Genomic, Habitat, and Leaf Shape Analyses Reveal a Possible Cryptic Species and Vulnerability to Climate Change in a Threatened Daisy
- 2021
-
Ingår i: Life. - : MDPI. - 2075-1729. ; 11:6
-
Tidskriftsartikel (refereegranskat)abstract
- Olearia pannosa is a plant species listed as vulnerable in Australia. Two subspecies are currently recognised (O. pannosa subsp. pannosa (silver daisy) and O. pannosa subsp. cardiophylla (velvet daisy)), which have overlapping ranges but distinct leaf shape. Remnant populations face threats from habitat fragmentation and climate change. We analysed range-wide genomic data and leaf shape variation to assess population diversity and divergence and to inform conservation management strategies. We detected three distinct genetic groupings and a likely cryptic species. Samples identified as O. pannosa subsp. cardiophylla from the Flinders Ranges in South Australia were genetically distinct from all other samples and likely form a separate, range-restricted species. Remaining samples formed two genetic clusters, which aligned with leaf shape differences but not fully with current subspecies classifications. Levels of genetic diversity and inbreeding differed between the three genetic groups, suggesting each requires a separate management strategy. Additionally, we tested for associations between genetic and environmental variation and carried out habitat suitability modelling for O. pannosa subsp. pannosa populations. We found mean annual maximum temperature explained a significant proportion of genomic variance. Habitat suitability modelling identified mean summer maximum temperature, precipitation seasonality and mean annual rainfall as constraints on the distribution of O. pannosa subsp. pannosa, highlighting increasing aridity as a threat for populations located near suitability thresholds. Our results suggest maximum temperature is an important agent of selection on O. pannosa subsp. pannosa and should be considered in conservation strategies. We recommend taxonomic revision of O. pannosa and provide conservation management recommendations.
|
|
| 37. |
|
|
| 38. |
- Busby, CJ, et al.
(författare)
-
The missing half of the subduction factory : shipboard results from the Izu rear arc, IODP expedition 350
- 2017
-
Ingår i: International Geology Review. - : Informa UK Limited. - 0020-6814 .- 1938-2839. ; 59:13, s. 1677-1708
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- IODP Expedition 350 was the first to be drilled in the rear part of the Izu-Bonin, although severalsites had been drilled in the arc axis to fore-arc region; the scientific objective was to understand theevolution of the Izu rear arc, by drilling a deep-water volcaniclastic section with a long temporalrecord (Site U1437). The Izu rear arc is dominated by a series of basaltic to dacitic seamount chainsup to ~100-km long roughly perpendicular to the arc front. Dredge samples from these aregeochemically distinct from arc front rocks, and drilling was undertaken to understand this arcasymmetry. Site U1437 lies in an ~20-km-wide basin between two rear arc seamount chains, ~90-kmwest of the arc front, and was drilled to 1804 m below the sea floor (mbsf) with excellent recovery.We expected to drill a volcaniclastic apron, but the section is much more mud-rich than expected(~60%), and the remaining fraction of the section is much finer-grained than predicted from itsposition within the Izu arc, composed half of ashes/tuffs, and half of lapilli tuffs of fine grain size(clasts <3 cm). Volcanic blocks (>6.4 cm) are only sparsely scattered through the lowermost 25% ofthe section, and only one igneous unit was encountered, a rhyolite peperite intrusion at~1390 mbsf. The lowest biostratigaphic datum is at 867 mbsf (~6.5 Ma), the lowest palaeomagneticdatum is at ~1300 mbsf (~9 Ma), and the rhyolite peperite at ~1390 mbsf has yielded a U–Pb zirconconcordia intercept age of (13.6 + 1.6/−1.7) Ma. Both arc front and rear arc sources contributed tothe fine-grained (distal) tephras of the upper 1320 m, but the coarse-grained (proximal) volcani-clastics in the lowest 25% of the section are geochemically similar to the arc front, suggesting arcasymmetry is not recorded in rocks older than ~13 Ma.
|
|
| 39. |
- Denoyes-Rothan, B., et al.
(författare)
-
Anthracnose on strawberry in France : Situation and perspectives
- 2006
-
Ingår i: Proceedings of the Vth International Strawberry Symposium. - : INTERNATIONAL SOCIETY HORTICULTURAL SCIENCE. ; , s. 277-280
-
Konferensbidrag (refereegranskat)abstract
- Anthracnose, caused by Colletotrichum acutatum, on strawberry (Fragaria x ananassa) was first reported on fruit in France in 1981. Damage was later recorded on runners, petioles, foliage and crowns. The evolution of a disease control method, the molecular variability of C acutatum, the study of the interaction between pathogen and host, the different techniques of inoculation, and the last results concerning QTLs linked to resistance to C acutatum are reported, which cover 10 years of research in France.
|
|
| 40. |
- Denoyes-Rothan, B, et al.
(författare)
-
QTL analysis for resistances to Colletotrichum acutatum and Phytophthora cactorum in octoploid strawberry (Fragaria x ananassa)
- 2004
-
Ingår i: Proceedings of the XIth Eucarpia Symposium on Fruit Breeding and Genetics, Vols 1 and 2. - : INTERNATIONAL SOCIETY HORTICULTURAL SCIENCE. ; , s. 147-151
-
Konferensbidrag (refereegranskat)abstract
- Colletotrichum acutatum and Phytophthora cactorum are two of the most important pathogens of strawberry in Europe, and particularly in France. The characterization of quantitative trait loci (QTL) controlling resistances to these two pathogens would allow a better knowledge of the genetic architecture of these resistances in order to develop durable resistance. A pseudo-testcross strawberry population derived from the cross between Capitola and CF1116 was used for detecting QTLs associated with C. acutatum and P cactorum resistances. One hundred and eighty five individuals were inoculated with C. acutatum by dipping cold stored plants in a conidial suspension adjusted to 2.10(6) conidia per ml. They were also inoculated separately with P cactorum by inserting an agar disk containing mycelium into the crown. Each inoculation was conducted twice. Putative QTLs for resistance to C acutatum and P cactorum were identified by Interval Mapping (Mapmaker-QTL) using a LOD threshold of 2.
|
|
| 41. |
- Filippatos, Gerasimos, et al.
(författare)
-
Global Differences in Characteristics, Precipitants, and Initial Management of Patients Presenting With Acute Heart Failure
- 2020
-
Ingår i: JAMA cardiology. - : AMER MEDICAL ASSOC. - 2380-6583 .- 2380-6591. ; 5:4, s. 401-410
-
Tidskriftsartikel (refereegranskat)abstract
- Question What are the key similarities and differences in characteristics, comorbidities, therapies, and in-hospital outcomes in patients with chronic and acute heart failure? Findings In this cohort study including 18& x202f;553 patients from 7 global regions, there were similarities in many regions regarding prevalence of prior heart failure, ejection fraction, and comorbidities. However, there were key differences in outpatient treatment, hospital point of entry, acute heart failure precipitants, and timing and type of inpatient intravenous therapies. Meaning These data provide information on the current global burden of acute heart failure, identify region-specific gaps in management, and note differences in practice around the world associated with patient outcomes. This cohort study compares the characteristics and management of acute heart failure in global regions comprising 44 countries. Importance Acute heart failure (AHF) precipitates millions of hospital admissions worldwide, but previous registries have been country or region specific. Objective To conduct a prospective contemporaneous comparison of AHF presentations, etiologic factors and precipitants, treatments, and in-hospital outcomes among global regions through the International Registry to Assess Medical Practice with Longitudinal Observation for Treatment of Heart Failure (REPORT-HF). Design, Setting, and Participants A total of 18& x202f;553 adults were enrolled during a hospitalization for AHF. Patients were recruited from the acute setting in Western Europe (WE), Eastern Europe (EE), Eastern Mediterranean and Africa (EMA), Southeast Asia (SEA), Western Pacific (WP), North America (NA), and Central and South America (CSA). Patients with AHF were approached for consent and excluded only if there was recent participation in a clinical trial. Patients were enrolled from July 23, 2014, to March 24, 2017. Statistical analysis was conducted from April 18 to June 29, 2018; revised analyses occurred between August 6 and 29, 2019. Main Outcomes and Measures Heart failure etiologic factors and precipitants, treatments, and in-hospital outcomes among global regions. Results A total of 18& x202f;553 patients were enrolled at 358 sites in 44 countries. The median age was 67.0 years (interquartile range [IQR], 57-77), 11& x202f;372 were men (61.3%), 9656 were white (52.0%), 5738 were Asian (30.9%), and 867 were black (4.7%). A history of HF was present in more than 50% of the patients and 40% were known to have a prior left-ventricular ejection fraction lower than 40%. Ischemia was a common AHF precipitant in SEA (596 of 2329 [25.6%]), WP (572 of 3354 [17.1%]), and EMA (364 of 2241 [16.2%]), whereas nonadherence to diet and medications was most common in NA (306 of 1592 [19.2%]). Median time to the first intravenous therapy was 3.0 (IQR, 1.4-5.6) hours in NA; no other region had a median time above 1.2 hours (P < .001). This treatment delay remained after adjusting for severity of illness (P < .001). Intravenous loop diuretics were the most common medication administered in the first 6 hours of AHF management across all regions (65.4%-89.9%). Despite similar initial blood pressure across all regions, inotropic agents were used approximately 3 times more often in SEA, WP, and EE (11.3%-13.5%) compared with NA and WE (3.1%-4.3%) (P < .001). Older age (odds ratio [OR], 1.0; 95% CI, 1.00-1.02), HF etiology (ischemia: OR, 1.65; 95% CI, 1.11-2.44; valvular: OR, 2.10; 95% CI, 1.36-3.25), creatinine level greater than 2.75 mg/dL (OR, 1.85; 95% CI, 0.71-2.40), and chest radiograph signs of congestion (OR, 2.03; 95% CI, 1.39-2.97) were all associated with increased in-hospital mortality. Similarly, younger age (OR, -0.04; 95% CI, -0.05 to -0.02), HF etiology (ischemia: OR, 0.77; 95% CI, 0.26-1.29; valvular: OR, 2.01; 95% CI, 1.38-2.65), creatinine level greater than 2.75 mg/dL (OR, 1.16; 95% CI, 0.31-2.00), and chest radiograph signs of congestion (OR, 1.02; 95% CI, 0.57-1.47) were all associated with increased in-hospital LOS. Conclusions and Relevance Data from REPORT-HF suggest that patients are similar across regions in many respects, but important differences in timing and type of treatment exist, identifying region-specific gaps in medical management that may be associated with patient outcomes.
|
|
| 42. |
|
|
| 43. |
- Hascoët, Sebastien, et al.
(författare)
-
Outcomes of transcatheter pulmonary SAPIEN 3 valve implantation: an international registry.
- 2023
-
Ingår i: European heart journal. - 1522-9645. ; 45:3, s. 198-210
-
Tidskriftsartikel (refereegranskat)abstract
- Transcatheter pulmonary valve implantation (TPVI) is indicated to treat right-ventricular outflow tract (RVOT) dysfunction related to congenital heart disease (CHD). Outcomes of TPVI with the SAPIEN 3 valve that are insufficiently documented were investigated in the EUROPULMS3 registry of SAPIEN 3-TPVI.Patient-related, procedural, and follow-up outcome data were retrospectively assessed in this observational cohort from 35 centres in 15 countries.Data for 840 consecutive patients treated in 2014-2021 at a median age of 29.2 (19.0-41.6) years were obtained. The most common diagnosis was conotruncal defect (70.5%), with a native or patched RVOT in 50.7% of all patients. Valve sizes were 20, 23, 26, and 29mm in 0.4%, 25.5%, 32.1%, and 42.0% of patients, respectively. Valve implantation was successful in 98.5% [95% confidence interval (CI), 97.4%-99.2%] of patients. Median follow-up was 20.3 (7.1-38.4) months. Eight patients experienced infective endocarditis; 11 required pulmonary valve replacement, with a lower incidence for larger valves (P = .009), and four experienced pulmonary valve thrombosis, including one who died and three who recovered with anticoagulation. Cumulative incidences (95%CI) 1, 3, and 6 years after TPVI were as follows: infective endocarditis, 0.5% (0.0%-1.0%), 0.9% (0.2%-1.6%), and 3.8% (0.0%-8.4%); pulmonary valve replacement, 0.4% (0.0%-0.8%), 1.3% (0.2%-2.4%), and 8.0% (1.2%-14.8%); and pulmonary valve thrombosis, 0.4% (0.0%-0.9%), 0.7% (0.0%-1.3%), and 0.7% (0.0%-1.3%), respectively.Outcomes of SAPIEN 3 TPVI were favourable in patients with CHD, half of whom had native or patched RVOTs.
|
|
| 44. |
- Hüpers, Andre, et al.
(författare)
-
Release of mineral-bound water prior to subduction tied to shallow seismogenic slip off Sumatra
- 2017
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 356:6340, s. 841-844
-
Tidskriftsartikel (refereegranskat)abstract
- Plate-boundary fault rupture during the 2004 Sumatra-Andaman subduction earthquake extended closer to the trench than expected, increasing earthquake and tsunami size. International Ocean Discovery Program Expedition 362 sampled incoming sediments offshore northern Sumatra, revealing recent release of fresh water within the deep sediments. Thermal modeling links this freshening to amorphous silica dehydration driven by rapid burial-induced temperature increases in the past 9 million years. Complete dehydration of silicates is expected before plate subduction, contrasting with prevailing models for subduction seismogenesis calling for fluid production during subduction. Shallow slip offshore Sumatra appears driven by diagenetic strengthening of deeply buried fault-forming sediments, contrasting with weakening proposed for the shallow Tohoku-Oki 2011 rupture, but our results are applicable to other thickly sedimented subduction zones including those with limited earthquake records.
|
|
| 45. |
|
|
| 46. |
- Kloprogge, F., et al.
(författare)
-
Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis
- 2018
-
Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 15:6
-
Tidskriftsartikel (refereegranskat)abstract
- Background The fixed dose combination of artemether-lumefantrine (AL) is the most widely used treatment for uncomplicated Plasmodium falciparum malaria. Relatively lower cure rates and lumefantrine levels have been reported in young children and in pregnant women during their second and third trimester. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of lumefantrine and the pharmacokinetic properties of its metabolite, desbutyl-lumefantrine, in order to inform optimal dosing regimens in all patient populations. A search in PubMed, Embase, ClinicalTrials. gov, Google Scholar, conference proceedings, and the WorldWide Antimalarial Resistance Network (WWARN) pharmacology database identified 31 relevant clinical studies published between 1 January 1990 and 31 December 2012, with 4,546 patients in whom lumefantrine concentrations were measured. Under the auspices of WWARN, relevant individual concentration-time data, clinical covariates, and outcome data from 4,122 patients were made available and pooled for the meta-analysis. The developed lumefantrine population pharmacokinetic model was used for dose optimisation through in silico simulations. Venous plasma lumefantrine concentrations 7 days after starting standard AL treatment were 24.2% and 13.4% lower in children weighing < 15 kg and 15-25 kg, respectively, and 20.2% lower in pregnant women compared with non-pregnant adults. Lumefantrine exposure decreased with increasing pre-treatment parasitaemia, and the dose limitation on absorption of lumefantrine was substantial. Simulations using the lumefantrine pharmacokinetic model suggest that, in young children and pregnant women beyond the first trimester, lengthening the dose regimen (twice daily for 5 days) and, to a lesser extent, intensifying the frequency of dosing (3 times daily for 3 days) would be more efficacious than using higher individual doses in the current standard treatment regimen (twice daily for 3 days). The model was developed using venous plasma data from patients receiving intact tablets with fat, and evaluations of alternative dosing regimens were consequently only representative for venous plasma after administration of intact tablets with fat. The absence of artemether-dihydroartemisinin data limited the prediction of parasite killing rates and recrudescent infections. Thus, the suggested optimised dosing schedule was based on the pharmacokinetic endpoint of lumefantrine plasma exposure at day 7. Our findings suggest that revised AL dosing regimens for young children and pregnant women would improve drug exposure but would require longer or more complex schedules. These dosing regimens should be evaluated in prospective clinical studies to determine whether they would improve cure rates, demonstrate adequate safety, and thereby prolong the useful therapeutic life of this valuable antimalarial treatment.
|
|
| 47. |
- Lerceteau-Köhler, Estelle, et al.
(författare)
-
Characterization of mixed disomic and polysomic inheritance in the octoploid strawberry (Fragaria x ananassa) using AFLP mapping
- 2003
-
Ingår i: Theoretical and Applied Genetics. - : SPRINGER-VERLAG. - 0040-5752 .- 1432-2242. ; 107:4, s. 619-628
-
Tidskriftsartikel (refereegranskat)abstract
- A two-way pseudo-testcross strategy, combined with Single Dose Restriction Fragment (SDRF) marker analysis, was used for genetic mapping in the octoploid cultivated strawberry Fragaria x ananassa (2n=8x=56). Based on a 113 full-sib progeny from a cross between the variety Capitola and the clone CF1116, we generated two parental maps using Amplified Fragment Length Polymorphism (AFLP) markers. Ninety two percent of the markers (727 out of 789) showed ratios corresponding to simplex markers (the majority being SDRF markers), and 8% (62 out of 789) fitted a multiplex ratio. Linkage maps were first established using SDRF markers in coupling phase. The female map comprised 235 markers distributed among 43 co-segregation groups, giving a map size of 1,604 cM. On the male map, 280 markers were assigned to 43 co-segregation groups, yielding a map size of 1,496 cM. Once the co-segregation groups were established, their association was tested using repulsion-phase markers. In total, taking into account associations representing the same linkage groups, 30 linkage groups were detected on the female side and 28 on the male side. On the female map, 68.3% of the pairwise marker linkages were in coupling versus 31.7% in repulsion phase, and the corresponding figures on the male map were 72.2% and 27.8%, respectively. In addition, both groups linked only in the coupling phase and groups linked in the repulsion phase were characterized. The observations suggest that the meiotic behavior of the F. x ananassa genome is neither fully disomic nor fully polysomic, but rather mixed. The genome may not be as completely diploidized as previously assumed.
|
|
| 48. |
- Lerceteau-Köhler, Estelle, et al.
(författare)
-
Development of a SCAR marker linked to dominant gene conferring resistance to Colletotrichum acutatum in strawberry (Fragaria x ananassa)
- 2003
-
Ingår i: BERRY CROP BREEDING, PRODUCTION AND UTILIZATION FOR A NEW CENTURY. - : INTERNATIONAL SOCIETY HORTICULTURAL SCIENCE. ; , s. 85-91
-
Konferensbidrag (refereegranskat)abstract
- Colletotrichum acutatum is responsible for strawberry anthracnose, one of the main disease of cultivated strawberry in the south-western area of France (60% of the French production). Anthracnose is a polycyclic disease for which no efficient disease control method has been developed. Therefore, the development of cultivars with sustainable resistance, i.e. efficient against the two pathogenicity groups, may be promising to lower both the level of damage and the use of chemicals. The objective of this study is to identify molecular markers linked to the major dominant gene conferring resistance to pathogenicity group 2 by using an approach of Bulk Segregant Analysis (BSA) and Amplified Fragment Length Polymorphisin (AFLP) markers. We identified four molecular markers, named mf1 to mf4, linked to the resistance gene to the pathogenicity group 2 of C. acutatum. Within a segregating population (back cross type) for the dominant gene, no recombination between the resistance allele and the marker mf3 was detected in 78 BC1 individuals studied. One Sequence Characterized Amplified Region (SCAR) obtained from mf4 (SCAR-mf4) provided a fast and easy test for selection of anthracnose resistant plants at early stage, with a misidentification rate of 1.3%. The evaluation of this SCAR marker in few strawberry varieties showed that only some resistant varieties possessed this marker.
|
|
| 49. |
- Lerceteau-Köhler, Estelle, et al.
(författare)
-
Identification of SCAR markers linked to Rca2 anthracnose resistance gene and their assessment in strawberry germplasm
- 2005
-
Ingår i: Theoretical and Applied Genetics. - : SPRINGER. - 0040-5752 .- 1432-2242. ; 111:5, s. 862-870
-
Tidskriftsartikel (refereegranskat)abstract
- Bulked segregant analysis combined with AFLPs was used to identify molecular markers linked to the Rca2 gene conferring resistance to Colletotrichum acutatum pathogenicity group 2 which causes anthracnose in the octoploid strawberry Fragaria x ananassa. DNA bulks originating from a cross between the resistant cultivar ‘Capitola’ and the susceptible cultivar ‘Pajaro’ were screened with 110 EcoRI/MseI AFLP combinations. Four AFLP markers were found linked in coupling phase to Rca2 with recombination percentages between 0% and 17.7%. Among the four markers linked to the resistance gene, two were converted into SCAR markers (STS-Rca2_417 and STS-Rca2_240) and screened in a large segregating population including 179 genotypes. The Rca2 resistance gene was estimated to be 0.6 cM from STS-Rca2_417 and 2.8 cM from STS-Rca2_240. The presence/absence of the two SCAR markers was further studied in 43 cultivars of F. x ananassa, including 14 susceptible, 28 resistant, and one intermediate genotype. Results showed that 81.4% and 62.8% of the resistant/susceptible genotypes were correctly predicted by using STS-Rca2_417 and STS-Rca2_240, respectively. The 14 susceptible genotypes showed no amplification for either SCARs. These developed SCARs constitute new tools for indirect selection criteria of anthracnose resistance genotypes in strawberry breeding programs.
|
|
| 50. |
- Lerceteau-Köhler, Estelle, et al.
(författare)
-
QTL analysis for fruit quality traits and resistance to Colletotrichum acutatum and Phytophthora cactorum in octoploid strawberry (Fragaria x ananassa)
- 2004
-
Ingår i: PROCEEDINGS OF THE EURO BERRY SYMPOSIUM - COST 836 FINAL WORSKHOP. - : INT SOC HORTICULTURAL SCIENCE. ; , s. 93-97
-
Konferensbidrag (refereegranskat)abstract
- Mapping of quantitative trait loci (QTL) controlling components of strawberry (Fragaria x ananassa Duch., 2n=8x=56) fruit quality and resistance to Colletotrichum acutatum and Phytophthora cactorum can be used to provide a better understanding of the genetic control of the traits, and to develop marker assisted selection for breeders. A segregating population of 213 individuals of a cross between ‘Capitola’ and ‘CF1116’, two genotypes with many contrasting fruit quality traits, was used for genetic mapping. ‘Capitola’ was resistant to the C. acutatum pathogenicity group 1 (pg1) and to P. cactorum while ‘CF1116’ was susceptible to C. acutatum and moderately susceptible to P. cactorum. Fruit quality was evaluated on a total of 34 traits, including developmental and fruit aspect related traits, texture related traits, fruit acidity, sugars, ascorbate and amino acid concentrations. Most of the traits except the amino acid concentrations were evaluated during two successive years. Disease responses to C. acutatum (pg2) and P. cactorum were evaluated using a scale from 0 (no observed symptom) to 5 (dead plant) in two successive independent experiments. Data were analysed for putative QTLs using MapQTL. For the fruit quality traits, a total of 22 significant QTLs were detected by simple interval mapping (LOD>3.0) in the first year of analyses and 17 were detected in the second year. Only two QTLs could be detected in both years. The percentages of phenotypic variance explained by each QTL ranged from 6.5% to 16.0%. For resistances, a total of nine QTLs was detected (LOD>2.0), 4 for resistance to C acutatum and 5 for resistance to P. cactorum with the percentage of variation explained by a QTL ranging from 6.5 to 12.2%. No QTL for the P. cactorum resistance overlapped the QTLs for the C acutatum resistance.
|
|
