| 1. |
- Lindborg, Erik, et al.
(författare)
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Comment on "reinterpreting aircraft measurement in anisotropic scaling turbulence" by Lovejoy et al. (2009)
- 2010
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 10:3, s. 1401-1402
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Tidskriftsartikel (refereegranskat)abstract
- Recently, Lovejoy et al. (2009) argued that the steep ∼k-3 atmospheric kinetic energy spectrum at synoptic scales (≥1000 km) observed by aircraft is a spurious artefact of aircraft following isobars instead of isoheights. Without taking into account the earth's rotation they hypothesise that the horizontal atmospheric energy spectrum should scale as k-5/3 at all scales. We point out that the approximate k -3-spectrum at synoptic scales has been observed by a number of non-aircraft means since the 1960s and that general circulation models and other current models have successfully produced this spectrum. We also argue that the vertical movements of the aircraft are far too small to cause any strong effect on the measured spectrum at synoptic scales.
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| 2. |
- Horne, B D, et al.
(författare)
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Pharmacogenetic warfarin dose refinements remain significantly influenced by genetic factors after one week of therapy
- 2012
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 107:2, s. 232-240
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Tidskriftsartikel (refereegranskat)abstract
- By guiding initial warfarin dose, pharmacogenetic (PGx) algorithms may improve the safety of warfarin initiation. However, once international normalised ratio (INR) response is known, the contribution of PGx to dose refinements is uncertain. This study sought to develop and validate clinical and PGx dosing algorithms for warfarin dose refinement on days 6-11 after therapy initiation. An international sample of 2,022 patients at 13 medical centres on three continents provided clinical, INR, and genetic data at treatment days 6-11 to predict therapeutic warfarin dose. Independent derivation and retrospective validation samples were composed by randomly dividing the population (80%/20%). Prior warfarin doses were weighted by their expected effect on S-warfarin concentrations using an exponential-decay pharmacokinetic model. The INR divided by that "effective" dose constituted a treatment response index . Treatment response index, age, amiodarone, body surface area, warfarin indication, and target INR were associated with dose in the derivation sample. A clinical algorithm based on these factors was remarkably accurate: in the retrospective validation cohort its R2 was 61.2% and median absolute error (MAE) was 5.0 mg/week. Accuracy and safety was confirmed in a prospective cohort (N=43). CYP2C9 variants and VKORC1-1639 G→A were significant dose predictors in both the derivation and validation samples. In the retrospective validation cohort, the PGx algorithm had: R2= 69.1% (p<0.05 vs. clinical algorithm), MAE= 4.7 mg/week. In conclusion, a pharmacogenetic warfarin dose-refinement algorithm based on clinical, INR, and genetic factors can explain at least 69.1% of therapeutic warfarin dose variability after about one week of therapy.
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| 3. |
- Lenzini, P., et al.
(författare)
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Integration of genetic, clinical, and INR data to refine warfarin dosing
- 2010
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Ingår i: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 87:5, s. 572-578
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Tidskriftsartikel (refereegranskat)abstract
- Well-characterized genes that affect warfarin metabolism (cytochrome P450 (CYP) 2C9) and sensitivity (vitamin K epoxide reductase complex 1 (VKORC1)) explain one-third of the variability in therapeutic dose before the international normalized ratio (INR) is measured. To determine genotypic relevance after INR becomes available, we derived clinical and pharmacogenetic refinement algorithms on the basis of INR values (on day 4 or 5 of therapy), clinical factors, and genotype. After adjusting for INR, CYP2C9 and VKORC1 genotypes remained significant predictors (P < 0.001) of warfarin dose. The clinical algorithm had an R(2) of 48% (median absolute error (MAE): 7.0 mg/week) and the pharmacogenetic algorithm had an R(2) of 63% (MAE: 5.5 mg/week) in the derivation set (N = 969). In independent validation sets, the R(2) was 26-43% with the clinical algorithm and 42-58% when genotype was added (P = 0.002). After several days of therapy, a pharmacogenetic algorithm estimates the therapeutic warfarin dose more accurately than one using clinical factors and INR response alone.
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| 4. |
- Woods, Niels-Bjarne, et al.
(författare)
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Efficient Generation of Hematopoietic Precursors and Progenitors From Human Pluripotent Stem Cell Lines.
- 2011
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Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 29:7, s. 1158-1164
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Tidskriftsartikel (refereegranskat)abstract
- By mimicking embryonic development of the hematopoietic system, we have developed an optimized in vitro differentiation protocol for the generation of precursors of hematopoietic lineages and primitive hematopoietic cells from human embryonic stem cells (ES) and induced pluripotent stem cells (iPS). Factors such as cytokines, extra cellular matrix components, and small molecules, as well as the temporal association and concentration of these factors were tested on seven different human ES and iPS lines. We report the differentiation of up to 84% huCD45+ cells (average 41% ± 16, from 7 pluripotent lines) from the differentiation culture, including significant numbers of primitive CD45+/CD34+ and CD45+/CD34+/CD38- hematopoietic progenitors. Moreover, the numbers of hematopoietic progenitor cells generated, as measured by colony forming unit assays were comparable to numbers obtained from fresh umbilical cord blood mononuclear cell isolates on a per CD45+ cell basis. Our approach demonstrates highly efficient generation of multipotent hematopoietic progenitors with the highest efficiencies reported to date (CD45+/CD34+) using a single standardized differentiation protocol on several human ES and iPS lines. Our data add to the cumulating evidence for the existence of an in vitro derived precursor to the hematopoietic stem cell (HSC) with limited engrafting ability in transplanted mice, but with multipotent hematopoietic potential. Because this protocol efficiently expands the pre-blood precursors and hematopoietic progenitors, it is ideal for testing novel factors for the generation and expansion of definitive HSCs with long-term repopulating ability.
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