| 1. |
- Hansson, E K, et al.
(författare)
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PKPD Modeling of VEGF, sVEGFR-2, sVEGFR-3, and sKIT as Predictors of Tumor Dynamics and Overall Survival Following Sunitinib Treatment in GIST
- 2013
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Ingår i: CPT. - : Wiley. - 2163-8306. ; 2, s. e84-
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Tidskriftsartikel (refereegranskat)abstract
- The predictive value of longitudinal biomarker data (vascular endothelial growth factor (VEGF), soluble VEGF receptor (sVEGFR)-2, sVEGFR-3, and soluble stem cell factor receptor (sKIT)) for tumor response and survival was assessed based on data from 303 patients with imatinib-resistant gastrointestinal stromal tumors (GIST) receiving sunitinib and/or placebo treatment. The longitudinal tumor size data were well characterized by a tumor growth inhibition model, which included, as significant descriptors of tumor size change, the model-predicted relative changes from baseline over time for sKIT (most significant) and sVEGFR-3, in addition to sunitinib exposure. Survival time was best described by a parametric time-to-event model with baseline tumor size and relative change in sVEGFR-3 over time as predictive factors. Based on the proposed modeling framework to link longitudinal biomarker data with overall survival using pharmacokinetic-pharmacodynamic models, sVEGFR-3 demonstrated the greatest predictive potential for overall survival following sunitinib treatment in GIST.
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| 2. |
- O'Gorman, Eoin J., et al.
(författare)
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Impacts of Warming on the Structure and Functioning of Aquatic Communities : Individual-to Ecosystem-Level Responses
- 2012
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Ingår i: Advances in Ecological Research, Vol 47. - : Elsevier. - 9780123983152 ; , s. 81-176
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Bokkapitel (refereegranskat)abstract
- Environmental warming is predicted to rise dramatically over the next century, yet few studies have investigated its effects in natural, multi-species systems. We present data collated over an 8-year period from a catchment of geothermally heated streams in Iceland, which acts as a natural experiment on the effects of warming across different organisational levels and spatiotemporal scales. Body sizes and population biomasses of individual species responded strongly to temperature, with some providing evidence to support temperature size rules. Macroinvertebrate and meiofaunal community composition also changed dramatically across the thermal gradient. Interactions within the warm streams in particular were characterised by food chains linking algae to snails to the apex predator, brown trout These chains were missing from the colder systems, where snails were replaced by much smaller herbivores and invertebrate omnivores were the top predators. Trout were also subsidised by terrestrial invertebrate prey, which could have an effect analogous to apparent competition within the aquatic prey assemblage. Top-down effects by snails on diatoms were stronger in the warmer streams, which could account for a shallowing of mass-abundance slopes across the community. This may indicate reduced energy transfer efficiency from resources to consumers in the warmer systems and/or a change in predator-prey mass ratios. All the ecosystem process rates investigated increased with temperature, but with differing thermal sensitivities, with important implications for overall ecosystem functioning (e.g. creating potential imbalances in elemental fluxes). Ecosystem respiration rose rapidly with temperature, leading to increased heterotrophy. There were also indications that food web stability may be lower in the warmer streams.
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| 3. |
- Ribba, B, et al.
(författare)
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A review of mixed-effects models of tumor growth and effects of anticancer drug treatment used in population analysis
- 2014
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Ingår i: CPT. - : Wiley. - 2163-8306. ; 3:5, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Population modeling of tumor size dynamics has recently emerged as an important tool in pharmacometric research. A series of new mixed-effects models have been reported recently, and we present herein a synthetic view of models with published mathematical equations aimed at describing the dynamics of tumor size in cancer patients following anticancer drug treatment. This selection of models will constitute the basis for the Drug Disease Model Resources (DDMoRe) repository for models on oncology.
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| 4. |
- Vicini, P, et al.
(författare)
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Pharmacometrics and Systems Pharmacology Software Tutorials and Use : Comments and Guidelines for PSP Contributions
- 2013
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Ingår i: CPT. - : Wiley. - 2163-8306. ; 2, s. e86-
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Tidskriftsartikel (refereegranskat)abstract
- In addition to methodological Tutorials,(1) CPT:PSP has recently started to publish software Tutorials.(2,3) Our readership and authors may be wondering what kind of format or product is expected, and the review of submissions we have already received prompted several discussions within the PSP Editorial Team. This editorial reflects on these discussions and summarizes their salient points. It aims at providing some details about the current vision of CPT:PSP for software tutorial articles. In addition, it brings some clarity on the topic of what role commercial software tutorials can have in CPT:PSP and how CPT:PSP tutorials differ from publications which describe the software itself, as those which can be found in other computer science journals. Finally, the discussion includes reproducibility considerations and the general use of commercial and noncommercial software in CPT:PSP publications. We hope our thoughts, and especially a stated requirement to publish user input to the software to aid in reproducibility, will help in guiding our authors and will stimulate healthy debate among our readers about the evolving nature of our science, how it can be facilitated using software and associated databases as a conduit, and what role this journal can play in fostering both the best modeling and simulation practices and the best scientific approaches to computational modeling, to bring the advantages of modeling and simulation to all regular practitioners, and not to just a (self) selected few.
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| 5. |
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| 6. |
- Bergmann, T K, et al.
(författare)
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Impact of CYP2C8*3 on paclitaxel clearance: a population pharmacokinetic and pharmacogenomic study in 93 patients with ovarian cancer
- 2011
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Ingår i: PHARMACOGENOMICS JOURNAL. - : Nature Publishing Group. - 1470-269X .- 1473-1150. ; 11:2, s. 113-120
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Tidskriftsartikel (refereegranskat)abstract
- The primary purpose of this study was to evaluate the effect of CYP2C8*3 and three genetic ABCB1 variants on the elimination of paclitaxel. We studied 93 Caucasian women with ovarian cancer treated with paclitaxel and carboplatin. Using sparse sampling and nonlinear mixed effects modeling, the individual clearance of unbound paclitaxel was estimated from total plasma paclitaxel and Cremophor EL. The geometric mean of clearance was 385 l h(-1) (range 176-726 l h(-1)). Carriers of CYP2C8*3 had 11% lower clearance than non-carriers, P = 0.03. This has not been shown before in similar studies; the explanation is probably the advantage of using both unbound paclitaxel clearance and a population of patients of same gender. No significant association was found for the ABCB1 variants C1236T, G2677T/A and C3435T. Secondarily, other candidate single-nucleotide polymorphisms were explored with possible associations found for CYP2C8*4 (P = 0.04) and ABCC1 g.7356253C andgt; G (P = 0.04).
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| 7. |
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| 8. |
- Hambraeus, Kristina, et al.
(författare)
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SWEDEHEART annual report 2012
- 2014
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa Healthcare. - 1401-7431 .- 1651-2006. ; 48:SUPPL. 63, s. 1-333
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) supports continuous monitoring and improvement of care for coronary artery disease, catheter-based and surgical coronary interventions, secondary prevention as well as catheter based and surgical valve intervention, by providing extensive data on base-line, diagnostic, procedural and outcome variables. Design. This national quality registry collects information from all Swedish hospitals treating patients with acute coronary artery disease and all patients undergoing coronary angiography, catheter-based interventions or heart surgery. Combination with other national mandatory official registries enables complete follow-up of all individuals regarding myocardial infarction, new interventional procedures, death and all-cause hospitalizations. The registry is governed by an independent steering committee and funded by the Swedish National Health care provider. The software is developed by Uppsala Clinical Research Center. Results. The SWEDEHEART Quality Index reflects overall quality of care for coronary artery disease including secondary prevention. In comparison with 2011, an improvement of the index occurred in 2012 overall. There was however, still a wide range in performance between individual centers, emphasizing the need for continuous monitoring of quality of care at a national as well as on a center level. © 2014 Informa Healthcare.
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| 9. |
- Hansson, E K, et al.
(författare)
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PKPD Modeling of Predictors for Adverse Effects and Overall Survival in Sunitinib-Treated Patients With GIST
- 2013
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Ingår i: CPT. - : Wiley. - 2163-8306. ; 2, s. e85-
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Tidskriftsartikel (refereegranskat)abstract
- A modeling framework relating exposure, biomarkers (vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor (sVEGFR)-2, -3, soluble stem cell factor receptor (sKIT)), and tumor growth to overall survival (OS) was extended to include adverse effects (myelosuppression, hypertension, fatigue, and hand-foot syndrome (HFS)). Longitudinal pharmacokinetic-pharmacodynamic models of sunitinib were developed based on data from 303 patients with gastrointestinal stromal tumor. Myelosuppression was characterized by a semiphysiological model and hypertension with an indirect response model. Proportional odds models with a first-order Markov model described the incidence and severity of fatigue and HFS. Relative change in sVEGFR-3 was the most effective predictor of the occurrence and severity of myelosuppression, fatigue, and HFS. Hypertension was correlated best with sunitinib exposure. Baseline tumor size, time courses of neutropenia, and relative increase of diastolic blood pressure were identified as predictors of OS. The framework has potential to be used for early monitoring of adverse effects and clinical response, thereby facilitating dose individualization to maximize OS.
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| 10. |
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