| 1. |
- Björkholm, Magnus, et al.
(författare)
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Success Story of Targeted Therapy in Chronic Myeloid Leukemia : A Population-Based Study of Patients Diagnosed in Sweden From 1973 to 2008
- 2011
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 29:18, s. 2514-2520
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Chronic myeloid leukemia (CML) management changed dramatically with the development of imatinib mesylate (IM), the first tyrosine kinase inhibitor targeting the BCR-ABL1 oncoprotein. In Sweden, the drug was approved in November 2001. We report relative survival (RS) of patients with CML diagnosed during a 36-year period. Patients and Methods Using data from the population-based Swedish Cancer Registry and population life tables, we estimated RS for all patients diagnosed with CML from 1973 to 2008 (n = 3,173; 1,796 males and 1,377 females; median age, 62 years). Patients were categorized into five age groups and five calendar periods, the last being 2001 to 2008. Information on use of upfront IM was collected from the Swedish CML registry. Results Relative survival improved with each calendar period, with the greatest improvement between 1994-2000 and 2001-2008. Five-year cumulative relative survival ratios (95% CIs) were 0.21 (0.17 to 0.24) for patients diagnosed 1973-1979, 0.54 (0.50 to 0.58) for 1994-2000, and 0.80 (0.75 to 0.83) for 2001-2008. This improvement was confined to patients younger than 79 years of age. Five-year RSRs for patients diagnosed from 2001 to 2008 were 0.91 (95% CI, 0.85 to 0.94) and 0.25 (95% CI, 0.10 to 0.47) for patients younger than 50 and older than 79 years, respectively. Men had inferior outcome. Upfront overall use of IM increased from 40% (2002) to 84% (2006). Only 18% of patients older than 80 years of age received IM as first-line therapy. Conclusion This large population-based study shows a major improvement in outcome of patients with CML up to 79 years of age diagnosed from 2001 to 2008, mainly caused by an increasing use of IM. The elderly still have poorer outcome, partly because of a limited use of IM.
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| 2. |
- Christensson, Anders, et al.
(författare)
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Association of cancer with moderately impaired renal function at baseline in a large, representative, population-based cohort followed for up to 30 years.
- 2013
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 133:6, s. 1452-1458
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Tidskriftsartikel (refereegranskat)abstract
- Patients with chronic renal failure show a greater incidence of malignancies. We evaluated whether moderately impaired renal function at baseline influenced risk of all cancers during long-term follow in young persons. Our cohort included 33,346 subjects, aged 26-61 years at baseline, in a representative, population-based study enrolling subjects from 1974 to 1992. Median follow-up time was 28 years. Plasma creatinine was analysed as a single measure at baseline. Incident cases of cancer were identified from the Swedish Cancer Registry. We studied 24,552 subjects from the cohort. To account for the unique sampling design, participants were divided by sex and age at baseline into 1,132 older men (age 60), 14,254 younger men (age 40-52), 7,498 older women (age 47-57) and 1,688 younger women (age 35-43). Glomerular filtration rate (GFR) was estimated using the CKD-EPI formula. Patients were classified as having either normal to mildly impaired kidney function (eGFR≥60 mL/min/1.73m(2) ), or moderate kidney dysfunction (eGFR<60 mL/min/1.73m(2) ). We calculated the risk of all cancers using competing risks regression. Overall, 6,595 participants were diagnosed with cancer, and 854 subjects (3.5%) had moderately impaired renal dysfunction at baseline. There was a significant association between moderately decreased GFR and subsequent risk of kidney cancer in younger men (hazard ratio, 3.38; 95% CI, 1.48 to 7.71; P=0.004). However, we found no association with overall long-term cancer risk. Our confirmation of an association between moderately impaired renal function and risk of kidney cancer in younger men requires further exploration of high-risk groups and biological mechanisms. © 2013 Wiley Periodicals, Inc.
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| 3. |
- Fange, David, et al.
(författare)
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Stochastic reaction-diffusion kinetics in the microscopic limit
- 2010
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:46, s. 19820-19825
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Tidskriftsartikel (refereegranskat)abstract
- Quantitative analysis of biochemical networks often requires consideration of both spatial and stochastic aspects of chemical processes. Despite significant progress in the field, it is still computationally prohibitive to simulate systems involving many reactants or complex geometries using a microscopic framework that includes the finest length and time scales of diffusion-limited molecular interactions. For this reason, spatially or temporally discretized simulations schemes are commonly used when modeling intracellular reaction networks. The challenge in defining such coarse-grained models is to calculate the correct probabilities of reaction given the microscopic parameters and the uncertainty in the molecular positions introduced by the spatial or temporal discretization. In this paper we have solved this problem for the spatially discretized Reaction-Diffusion Master Equation; this enables a seamless and physically consistent transition from the microscopic to the macroscopic frameworks of reaction-diffusion kinetics. We exemplify the use of the methods by showing that a phosphorylation-dephosphorylation motif, commonly observed in eukaryotic signaling pathways, is predicted to display fluctuations that depend on the geometry of the system.
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| 4. |
- Gustafsson, Lars L., et al.
(författare)
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The 'wise list'- a comprehensive concept to select, communicate and achieve adherence to recommendations of essential drugs in ambulatory care in Stockholm
- 2011
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - Copenhagen : Blackwell Publishing. - 1742-7835 .- 1742-7843. ; 108:4, s. 224-233
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to present and evaluate the impact of a comprehensive strategy over 10 years to select, communicate and achieve adherence to essential drug recommendations (EDR) in ambulatory care in a metropolitan healthcare region. EDRs were issued and launched as a 'Wise List' by the regional Drug and Therapeutics Committee in Stockholm. This study presents the concept by: (i) documenting the process for selecting, communicating and monitoring the impact of the 'Wise List'; (ii) analysing the variation in the number of drug substances recommended between 2000 and 2010; (iii) assessing the attitudes to the 'Wise List' among prescribers and the public; (iv) evaluating the adherence to recommendations between 2003 and 2009. The 'Wise List' consistently contained 200 drug substances for treating common diseases. The drugs were selected based on their efficacy, safety, suitability and cost-effectiveness. The 'Wise List' was known among one-third of a surveyed sample of the public in 2002 after initial marketing campaigns. All surveyed prescribers knew about the concept and 81% found the recommendations trustworthy in 2005. Adherence to recommendations increased from 69% in 1999 to 77% in 2009. In primary care, adherence increased from 83% to 87% from 2003 to 2009. The coefficient of variation (CV%) decreased from 6.1% to 3.8% for 156 healthcare centres between these years. The acceptance of the 'Wise List' in terms of trust among physicians and among the public and increased adherence may be explained by clear criteria for drug recommendations, a comprehensive communication strategy, electronic access to recommendations, continuous medical education and involvement of professional networks and patients.
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| 5. |
- Powell, Kipton J., et al.
(författare)
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Chemical speciation of environmentally significant metals with inorganic ligands. Part 5: The Zn2+ + OH–, Cl–, CO32–, SO42–, and PO43– systems (IUPAC Technical Report)
- 2013
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Ingår i: Pure and Applied Chemistry. - 0033-4545 .- 1365-3075. ; 85:12, s. 2249-2311
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Tidskriftsartikel (refereegranskat)abstract
- The numerical modeling of ZnII speciation amongst the environmental inorganic ligands Cl–, OH–, CO32–, SO42–, and PO43– requires reliable values for the relevant stability (formation) constants. This paper compiles and provides a critical review of these constants and related thermodynamic data. It recommends values of log10 βp,q,r° valid at Im = 0 mol·kg–1 and 25 °C (298.15 K), and reports the empirical reaction ion interaction coefficients, ∆ε, required to calculate log10 βp,q,r values at higher ionic strengths using the Brønsted–Guggenheim–Scatchard specific ion interaction theory (SIT). Values for the corresponding reaction enthalpies, ∆rH, are reported where available. There is scope for additional high-quality measurements for the Zn2+ + H+ + CO32– system and for the Zn2+ + OH– and Zn2+ + SO42– systems at I > 0. In acidic and weakly alkaline fresh water systems (pH < 8), in the absence of organic ligands (e.g., humic substances), ZnII speciation is dominated by Zn2+(aq). In this respect, ZnII contrasts with CuII and PbII (the subjects of earlier reviews in this series) for which carbonato- and hydroxido- complex formation become important at pH > 7. The speciation of ZnII is dominated by ZnCO3(aq) only at pH > 8.4. In seawater systems, the speciation at pH = 8.2 is dominated by Zn2+(aq) with ZnCl+, Zn(Cl)2(aq), ZnCO3(aq), and ZnSO4(aq) as minor species. This behaviour contrasts with that for CuII and PbII for which at the pH of seawater in equilibrium with the atmosphere at 25 °C (log10 {[H+]/c°} ≈ 8.2) the MCO3(aq) complex dominates over the MCln(2–n)+ species. The lower stability of the different complexes of ZnII compared with those of CuII, PbII, and CdII is also illustrated by the percentage of uncomplexed M2+ in seawater, which is ca. 55, 3, 2, and 3.3 % of [MII]T, respectively.
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| 6. |
- Powell, Kipton J, et al.
(författare)
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Chemical speciation of environmentally significant metals with inorganic ligands : Part 4: The Cd2+ + OH–, Cl–, CO32–, SO42–, and PO43– systems (IUPAC Technical Report)
- 2011
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Ingår i: Pure and Applied Chemistry. - 0033-4545 .- 1365-3075. ; 83:5, s. 1163-1214
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Tidskriftsartikel (refereegranskat)abstract
- The numerical modeling of CdII speciation amongst the environmental inorganic ligands Cl–, OH–, CO32–, SO42–, and PO43– requires reliable values for the relevant stability (formation) constants. This paper compiles and provides a critical review of these constants and related thermodynamic data. It recommends values of log10 βp,q,r° valid at Im = 0 mol kg–1 and 25 °C (298.15 K), along with the equations and empirical reaction ion interaction coefficients, ∆ε , required to calculate log10 βp,q,r values at higher ionic strengths using the Brønsted–Guggenheim–Scatchard specific ion interaction theory (SIT). Values for the corresponding reaction enthalpies, ∆rH, are reported where available. Unfortunately, with the exception of the CdII-chlorido system and (at low ionic strengths) the CdII-sulfato system, the equilibrium reactions for the title systems are relatively poorly characterized. In weakly acidic fresh water systems (–log10 {[H+]/c°} < 6), in the absence of organic ligands (e.g., humic substances), CdII speciation is dominated by Cd2+(aq), with CdSO4(aq) as a minor species. In this respect, CdII is similar to CuII [2007PBa] and PbII [2009PBa]. However, in weakly alkaline fresh water solutions, 7.5 < –log10 {[H+]/c°} < 8.6, the speciation of CdII is still dominated by Cd2+(aq), whereas for CuII [2007PBa] and PbII [2009PBa] the carbonato- species MCO3(aq) dominates. In weakly acidic saline systems (–log10 {[H+]/cϒ} < 6; –log10 {[Cl–]/c°} < 2.0) the speciation is dominated by CdCln(2–n)+ complexes, (n = 1–3), with Cd2+(aq) as a minor species. This is qualitatively similar to the situation for CuII and PbII. However, in weakly alkaline saline solutions, including seawater, the chlorido- complexes still dominate the speciation of CdII because of the relatively low stability of CdCO3(aq). In contrast, the speciation of CuII [2007PBa] and PbII [2009PBa] in seawater is dominated by the respective species MCO3(aq). There is scope for additional high-quality measurements in the Cd2+ + H+ + CO32– system as the large uncertainties in the stability constants for the Cd2+-carbonato complexes significantly affect the speciation calculations.
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| 7. |
- Sjöberg, Ted
(författare)
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Plasticity modelling of nickel based super alloy Alloy 718
- 2014
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The ever growing demand on reduced fuel consumption in modern aircrafts puts high requirements on manufacturers to reduce weight in all parts of the aircraft. With a total weight of up to one fifth of an aircraft’s total operating weight, ways to decrease the weight of the engine systems are continuously sought. The containment structure that surrounds the fan and turbine in larger commercial aircrafts is designed to prevent any debris to escape and damage any other systems such as fuel tanks or fuselage in the event that a blade should come off. This structure adds considerable bulk to the engine and because of the importance of the containment structure any redesign needs to be thoroughly tested. The high costs associated with containment testing means industry is looking into the feasibility of substituting parts of the expensive experimental testing with more economical numerical simulations. In this thesis modelling of the plastic behaviour of the nickel based super alloy, called Alloy 718, is investigated in an effort to correctly model the material in numerical simulations. This material is one of the most widely used materials in the parts of an aircraft engine subjected to elevated temperatures due to its retained strength and resistance to corrosion and creep. The material models chosen to model the plastic behaviour were the widely used Johnson-Cook and Zerilli-Armstrong models, because of their proven applicability for wide ranges of strain rates. The models were calibrated using data collected from tensile testing performed in a high speed VHS machine from Instron. Tensile tests were performed at quasi-static conditions and raised strain rates up to 1000 s-1. With an induction coil testing was also performed at temperatures up to 650 oC. Fitting the models to the data gave models valid from quasi-static to high rate conditions. In order to test the accuracy of the models they need to be validated. For this purpose a reverse impact experiment using free flying discs impacting a long slender rod was designed. This design enables the force history to be accurately monitored throughout the impact, while still achieving high strain rates. An investigation into producing additional data for use in validation was also performed. This investigation utilized a series of high speed photographs on which shape measurements were carried out in order to find parameters such as plate velocity and average strain without interfering with the experimental results
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