| 1. |
- Borgå, Olof, et al.
(författare)
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Maximum Tolerated Dose and Pharmacokinetics of Paclitaxel Micellar in Patients with Recurrent Malignant Solid Tumours : A Dose-Escalation Study
- 2019
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Ingår i: Advances in Therapy. - : Springer. - 0741-238X .- 1865-8652. ; 36:5, s. 1150-1163
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: A water-soluble Cremophor EL-free formulation of paclitaxel, in which retinoic acid derivates solubilize paclitaxel by forming micelles (paclitaxel micellar), was studied for the first time in man to establish the maximum tolerated dose (MTD) and to characterize the pharmacokinetics (PK).Methods: This was an open-label, one-arm, dose-escalating study in patients with advanced solid malignant tumours, for which no standard therapy was available or had failed. Paclitaxel micellar was given as 1-h intravenous infusion every 21 days for 3 cycles, mainly without premedication. Plasma samples were collected during 24 h at the first cycle and paclitaxel concentrations were assayed by high-performance liquid chromatography. PK was evaluated using a two-compartment model.Results: Thirty-four patients received paclitaxel micellar at doses ranging between 90 and 275 mg/m2. MTD was established as 250 mg/m2. Fatigue and neuropathy were the most frequent dose-limiting toxicities. No hypersensitivity reactions were observed. PK of paclitaxel was evaluated in 25 data sets. Paclitaxel micellar had a rapid initial distribution phase, mean half-life 0.55 h, estimated to be completed 3 h after dosing and a mean terminal half-life of 8.8 h. Mean clearance was 13.4 L/h/m2 with fivefold interindividual variability. The residual areas after 10 h and 24 h were 15.7 ± 8.6% and 5.7 ± 3.9% of the area under the plasma concentration–time curve to infinite time (AUCinf), respectively.Conclusion: No new side effects unknown for paclitaxel were observed. Maximum plasma concentration (Cmax) and AUCinf showed a tendency to increase linearly with dose within the 150–275 mg/m2dose range. The possibility to administer paclitaxel micellar without steroid premedication makes it an attractive candidate for further studies in combination with immunotherapy.Trial Registration: EudraCT no: 2004-001821-54.
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| 2. |
- Lindqvist, C Mårten, et al.
(författare)
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The Mutational Landscape in Pediatric Acute Lymphoblastic Leukemia Deciphered by Whole Genome Sequencing
- 2015
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 36:1, s. 118-128
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Tidskriftsartikel (refereegranskat)abstract
- Genomic characterization of pediatric acute lymphoblastic leukemia (ALL) has identified distinct patterns of genes and pathways altered in patients with well-defined genetic aberrations. To extend the spectrum of known somatic variants in ALL, we performed whole genome and transcriptome sequencing of three B-cell precursor patients, of which one carried the t(12;21)ETV6-RUNX1 translocation and two lacked a known primary genetic aberration, and one T-ALL patient. We found that each patient had a unique genome, with a combination of well-known and previously undetected genomic aberrations. By targeted sequencing in 168 patients, we identified KMT2D and KIF1B as novel putative driver genes. We also identified a putative regulatory non-coding variant that coincided with overexpression of the growth factor MDK. Our results contribute to an increased understanding of the biological mechanisms that lead to ALL and suggest that regulatory variants may be more important for cancer development than recognized to date. The heterogeneity of the genetic aberrations in ALL renders whole genome sequencing particularly well suited for analysis of somatic variants in both research and diagnostic applications.
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| 3. |
- Magnusson, Hans, 1943-, et al.
(författare)
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Integrating prehydrolysis kraft pulping of softwood and viscose fibre manufacturing
- 2016
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Ingår i: Appita journal. - Macleod Vic, Australia : Appita, Inc.. - 1038-6807. ; 69:3, s. 264-272
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Tidskriftsartikel (refereegranskat)abstract
- This work investigates the potential to integrate modern viscose manufacturing with prehydrolysis kraft pulping in order to improve the economic and environmental feasibility for production of regenerate cellulose fibers from wood. The study is largely based on calculations from literature data, but key stages are also tested experimentally. It is concluded that a kraft pulp mill can supply the acid demands of the viscose plant via acetic acid formed in the prehydrolysis and sulphuric acid for coagulation, with alkali for mercerization and dissolution, and it can also take care of spent liquors from the viscose plant. The pulp used for regenerated cellulose manufacture is delivered as wet pulp from the pulp mill, no drying is needed and a considerable amount of energy is saved. However, in an integrated production the viscose mill cannot use the whole production of cellulose from the kraft mill. One method of removing zinc ions from the coagulation bath effluents, based on precipitation of zinc sulphide via a well-controlled addition of green liquor from the pulp mill, has been studied.
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| 4. |
- Mattsson, Tuve, et al.
(författare)
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The Development of a Wood-based Materials-biorefinery
- 2017
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Ingår i: BioResources. - : North Carolina State University. - 1930-2126. ; 12:4, s. 9152-9182
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Tidskriftsartikel (refereegranskat)abstract
- Several different methods for the extraction, separation, and purification of wood constituents were combined in this work as a unified process with the purpose of achieving a high overall efficiency of material extraction and utilization. This study aimed to present a laboratory-scale demonstrator biorefinery that illustrated how the different wood constituents could be separated from the wood matrix for later use in the production of new bio-based materials and chemicals by combining several approaches. This study builds on several publications and ongoing activities within the Wallenberg Wood Science Center (WWSC) in Sweden on the theme "From wood to material components." Combining the approaches developed in these WWSC projects - including mild steam explosion, membrane and chromatographic separation, enzymatic treatment and leaching, ionic liquid extraction, and fractionation together with Kraft pulping - formed an outline for a complete materials-biorefinery. The process steps involved were tested as integral steps in a linked process. The scale of operations ranged from the kilogram-scale to the gram-scale. The feasibility and efficiency of these process steps in a biorefinery system were assessed, based on the data, beginning with whole wood.
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| 5. |
- Mattsson, Tuve, 1979, et al.
(författare)
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The Development of a Wood-based Materials-biorefinery
- 2017
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Ingår i: BioResources. - : BioResources. - 1930-2126 .- 1930-2126. ; 12:4, s. 9152-9182
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Tidskriftsartikel (refereegranskat)abstract
- Several different methods for the extraction, separation, and purification of wood constituents were combined in this work as a unified process with the purpose of achieving a high overall efficiency of material extraction and utilization. This study aimed to present a laboratory-scale demonstrator biorefinery that illustrated how the different wood constituents could be separated from the wood matrix for later use in the production of new bio-based materials and chemicals by combining several approaches. This study builds on several publications and ongoing activities within the Wallenberg Wood Science Center (WWSC) in Sweden on the theme "From wood to material components." Combining the approaches developed in these WWSC projects - including mild steam explosion, membrane and chromatographic separation, enzymatic treatment and leaching, ionic liquid extraction, and fractionation together with Kraft pulping - formed an outline for a complete materials-biorefinery. The process steps involved were tested as integral steps in a linked process. The scale of operations ranged from the kilogram-scale to the gram-scale. The feasibility and efficiency of these process steps in a biorefinery system were assessed, based on the data, beginning with whole wood.
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| 6. |
- Mattsson, Tuve, et al.
(författare)
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Towards a wood based material biorefinery - A demonstrator
- 2015
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Ingår i: 6th Nordic Wood Biorefinery Conference, NWBC 2015. - : VTT Technical Research Centre of Finland. - 9789513883539 ; , s. 92-101
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Konferensbidrag (refereegranskat)abstract
- Wood, the most abundant ligno-cellulosic raw material available, is a key potential feedstock for production of more sustainable alternatives to fossil-based materials. However advances within the fields of extraction and treatment processes within what is often referred to as the biorefinery concept is essential to allow for such transition. In this study, several different methods for the extraction and separation of wood constituents have been combined in a single process with the purpose of achieving a high overall efficiency of material extraction and utilisation. The work builds on several activities within the Wallenberg Wood Science Center (WWSC). The aim is to present a laboratory-scale demonstrator that illustrates how the different constituents can be separated from the wood matrix for later use in the production of bio-based materials and chemicals. The process steps involved have been tested as integral steps in a linked process for a scale of operations that range from the kilogram-scale down to the gram-scale. Industrially chipped softwood, containing mainly spruce with some pine, was used as raw material.
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| 7. |
- Nilsson, Martin P., et al.
(författare)
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BRCAsearch : written pre-test information and BRCA1/2 germline mutation testing in unselected patients with newly diagnosed breast cancer
- 2018
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 168:1, s. 117-126
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate a simplified method of pre-test information and germline BRCA1/2 mutation testing. Methods: In a prospective, single-arm study, comprehensive BRCA1/2 testing was offered to unselected patients with newly diagnosed breast cancer at three hospitals in south Sweden (BRCAsearch, ClinicalTrials.gov Identifier: NCT02557776). Pre-test information was provided by a standardized invitation letter, but the patients could contact a genetic counselor for telephone genetic counseling if they felt a need for that. Noncarriers were informed about the test result through a letter. Mutation carriers were contacted and offered an appointment for in-person post-test genetic counseling. Results: During the period Feb 2, 2015–Aug 26, 2016, eight hundred and eighteen patients were invited to participate in the study. Through Jan 31, 2017, five hundred and forty-two (66.2%) of them consented to analysis of BRCA1 and BRCA2. Eleven pathogenic mutations were found (BRCA1, n = 2; BRCA2, n = 9), corresponding to a mutation prevalence of 2.0%. Six out of 11 fulfilled the Swedish BRCA testing criteria, and 9 out of 11 fulfilled the NCCN testing criteria. None of the BRCA-associated tumors were of the luminal A-like subtype. Very few patients contacted us for telephone genetic counseling or practical questions, suggesting that a majority felt that the written pre-test information was sufficient for them to make a decision on testing. Conclusions: Streamlining the process of pre-test information, genetic testing, and delivery of test results was feasible and was associated with an uptake of genetic testing in 2/3 of the breast cancer patients.
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| 8. |
- Röijezon, Ulrik, et al.
(författare)
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An Initial Study on the Coordination of Rod and Line Hauling Movements in Distance Fly Casting
- 2017
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Ingår i: Annals of Applied Sport Science. - : Asian Exercise and Sport Science Association. - 2476-4981 .- 2322-4479. ; 5:2, s. 61-72
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Tidskriftsartikel (refereegranskat)abstract
- Background. The double haul is a unique feature of single-handed fly casting and is used in both fly fishing and fly casting competition. The movement behaviour during the double haul has not been investigated in previous research.Objectives. Describe the coordination of the rod and line hauling movements during distance fly casting.Methods. Elite fly casters performed distance casting with four different fly rod and fly line set-ups used in fly fishing and fly casting competition. Rod and hauling movements were measured with a 3D motion analysis system.Results. The rod and line hauling movements were coordinated in an order whereby peak translational speed of the rod occurs prior to the peak speed of the angular rotation of the rod, and the peak speed of the angular rotation of the rod occurs prior to the peak speed of the line haul. This was consistent for all cast sequences, i.e., the back and forward false casts and the delivery cast, and for all four equipment set-ups, i.e., a shooting-head line cast with a relatively stiff fly rod and a long-belly line cast with three different fly rods with different stiffness and action curves. Results also showed differences in movement coordination between cast sequences and rod and line set-ups.Conclusion. Among elite casters, single-handed fly casting with double haul is coordinated in an order of events whereby the peak speed occurs first for the translation of the rod, then for the rotation of the rod and finally for the line haul.
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