| 1. |
- Dong, Jin, et al.
(författare)
-
Understanding Statin-Roxadustat Drug–Drug-Disease Interaction Using Physiologically-Based Pharmacokinetic Modeling
- 2023
-
Ingår i: Clinical Pharmacology and Therapeutics. - : John Wiley & Sons. - 0009-9236 .- 1532-6535. ; 114:4, s. 825-835
-
Tidskriftsartikel (refereegranskat)abstract
- A different drug–drug interaction (DDI) scenario may exist in patients with chronic kidney disease (CKD) compared with healthy volunteers (HVs), depending on the interplay between drug–drug and disease (drug-drug-disease interaction (DDDI)). Physiologically-based pharmacokinetic (PBPK) modeling, in lieu of a clinical trial, is a promising tool for evaluating these complex DDDIs in patients. However, the prediction confidence of PBPK modeling in the severe CKD population is still low when nonrenal pathways are involved. More mechanistic virtual disease population and robust validation cases are needed. To this end, we aimed to: (i) understand the implications of severe CKD on statins (atorvastatin, simvastatin, and rosuvastatin) pharmacokinetics (PK) and DDI; and (ii) predict untested clinical scenarios of statin-roxadustat DDI risks in patients to guide suitable dose regimens. A novel virtual severe CKD population was developed incorporating the disease effect on both renal and nonrenal pathways. Drug and disease PBPK models underwent a four-way validation. The verified PBPK models successfully predicted the altered PKs in patients for substrates and inhibitors and recovered the observed statin-rifampicin DDIs in patients and the statin-roxadustat DDIs in HVs within 1.25- and 2-fold error. Further sensitivity analysis revealed that the severe CKD effect on statins PK is mainly mediated by hepatic BCRP for rosuvastatin and OATP1B1/3 for atorvastatin. The magnitude of statin-roxadustat DDI in patients with severe CKD was predicted to be similar to that in HVs. PBPK-guided suitable dose regimens were identified to minimize the risk of side effects or therapeutic failure of statins when co-administered with roxadustat.
|
|
| 2. |
|
|
| 3. |
- Garcia, Luna Prieto, et al.
(författare)
-
Does the choice of applied physiologically-based pharmacokinetics platform matter? : A case study on simvastatin disposition and drug-drug interaction
- 2022
-
Ingår i: CPT. - : John Wiley & Sons. - 2163-8306. ; 11:9, s. 1194-1209
-
Tidskriftsartikel (refereegranskat)abstract
- Physiologically-based pharmacokinetic (PBPK) models have an important role in drug discovery/development and decision making in regulatory submissions. This is facilitated by predefined PBPK platforms with user-friendly graphical interface, such as Simcyp and PK-Sim. However, evaluations of platform differences and the potential implications for disposition-related applications are still lacking. The aim of this study was to assess how PBPK model development, input parameters, and model output are affected by the selection of PBPK platform. This is exemplified via the establishment of simvastatin PBPK models (workflow, final models, and output) in PK-Sim and Simcyp as representatives of established whole-body PBPK platforms. The major finding was that the choice of PBPK platform influenced the model development strategy and the final model input parameters, however, the predictive performance of the simvastatin models was still comparable between the platforms. The main differences between the structure and implementation of Simcyp and PK-Sim were found in the absorption and distribution models. Both platforms predicted equally well the observed simvastatin (lactone and acid) pharmacokinetics (20-80 mg), BCRP and OATP1B1 drug-gene interactions (DGIs), and drug-drug interactions (DDIs) when co-administered with CYP3A4 and OATP1B1 inhibitors/inducers. This study illustrates that in-depth knowledge of established PBPK platforms is needed to enable an assessment of the consequences of PBPK platform selection. Specifically, this work provides insights on software differences and potential implications when bridging PBPK knowledge between Simcyp and PK-Sim users. Finally, it provides a simvastatin model implemented in both platforms for risk assessment of metabolism- and transporter-mediated DGIs and DDIs.
|
|
| 4. |
- Thörn, Helena Anna, et al.
(författare)
-
Drug metabolism of CYP3A4, CYP2C9 and CYP2D6 substrates in pigs and humans
- 2011
-
Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 43:3, s. 89-98
-
Tidskriftsartikel (refereegranskat)abstract
- Pigs are becoming increasingly used as a test animal both in pharmacological and toxicological assessment of new drug compounds. For interspecies comparisons and predictions it is important to characterize the expression and function of membrane transport and enzymatic proteins in pigs, particularly at a mechanistic level which will make extrapolation of observation between pig and man to be made with more confidence. The major objective of this report was to increase the integrative knowledge of drug metabolism in pigs and to compare with corresponding data from human liver microsomes. This was done by using human substrates of CYP3A4 (verapamil and testosterone), CYP2C9 (diclofenac) and CYP2D6 (dextromethorphan). In addition, the mRNA expression of important drug metabolizing enzymes and carrier-mediated transporters were assessed in intestine and liver tissues from pigs. It was shown that CYP3A4 activity is quantitatively comparable between the two species but data suggest that qualitative differences may exist. Verapamil showed similar metabolism pattern as in humans and the CYP3A4 inhibitor ketoconazole was able to inhibit the depletion of both R- and S-verapamil. A correlation between individual pig CYP3A mRNA expression and in vivo hepatic extraction ratio was established which indicates that CYP3A is the major determinant factor in both pigs and humans. However, investigations of the metabolism of testosterone resulted in qualitative different metabolite pattern between pigs and humans. The metabolism of diclofenac was very low in pig liver microsomes and did not correlate to corresponding activity in human liver microsomes. In contrast dextromethorphan exhibited a very extensive and rapid metabolism in pig liver microsomes compared to human data. Together with previously determined gene expression data it confirms that CYP2D6 substrates will be very rapidly metabolized in pigs. The mRNA data increased the knowledge of the interindividual variability and the relative expression of different enzymes and transporters in pig intestine and liver. In conclusion, this study has increased the understanding of similarities and differences between pig and human biotransformation of drugs by providing new data for four different model compounds.
|
|
| 5. |
- Aljadi, Zenib, et al.
(författare)
-
A novel tool for clinical diagnosis of allergy operating a microfluidic immunoaffinity basophil activation test technique
- 2019
-
Ingår i: Clinical Immunology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1521-6616 .- 1521-7035. ; 209
-
Tidskriftsartikel (refereegranskat)abstract
- The Basophil Activation Test (BAT) is a valuable allergy diagnostic tool but is time-consuming and requires skilled personnel and cumbersome processing, which has limited its clinical use. We therefore investigated if a microfluidic immunoaffinity BAT (miBAT) technique can be a reliable diagnostic method. Blood was collected from allergic patients and healthy controls. Basophils were challenged with negative control, positive control (anti-FccRI), and two concentrations of a relevant and non-relevant allergen. CD203c and CD63 expression was detected by fluorescent microscopy and flow cytometry. In basophils from allergic patients the CD63% was significantly higher after allergen activation as compared to the negative control (p < .0001-p = .0004). Activation with non-relevant allergen showed equivalent CD63% expression as the negative control. Further, the miBAT data were comparable to flow cytometry. Our results demonstrate the capacity of the miBAT technology to measure different degrees of basophil allergen activation by quantifying the CD63% expression on captured basophils.
|
|
| 6. |
- Aljadi, Zenib, et al.
(författare)
-
Activation of Basophils Is a New and Sensitive Marker of Biocompatibility in Hemodialysis
- 2014
-
Ingår i: Artificial Organs. - : Wiley. - 0160-564X .- 1525-1594. ; 38:11, s. 945-953
-
Tidskriftsartikel (refereegranskat)abstract
- The hemodialysis procedure involves contact between peripheral blood and the surface of dialyzer membranes, which may lead to alterations in the pathways of innate and adaptive immunity. We aimed to study the effect of blood-membrane interaction on human peripheral basophils and neutrophils in hemodialysis with high- and low-permeability polysulfone dialyzers. The surface expression of CD203c (basophil selection marker) and CD63 (activation marker) after activation by the bacterial peptide formyl-methionyl-leucyl-phenylalanine (fMLP) or anti-Fc epsilon receptor I (Fc epsilon RI) antibody and the absolute number of basophils was investigated before and after hemodialysis with each of the dialyzers. Moreover, the expression on neutrophils of CD11b, the CD11b active epitope, and CD88 was analyzed in the same groups of individuals. The expression of CD63 in basophils following activation by fMLP was significantly higher in the patient group compared with that in healthy controls, but no differences were observed after activation by anti-Fc epsilon RI. During the hemodialysis procedure, the low-flux membrane induced up-regulation of CD63 expression on basophils, while passage through the high-flux membrane did not significantly alter the responsiveness. In addition, the absolute number of basophils was unchanged after hemodialysis with either of the dialyzers and compared with healthy controls. We found no significant differences in the expression of the neutrophil activation markers (CD11b, the active epitope of CD11b, and CD88) comparing the two different dialyzers before and after dialysis and healthy controls. Together, these findings suggest that alterations in basophil activity may be a useful marker of membrane bioincompatibility in hemodialysis.
|
|
| 7. |
- Aljadi, Zenib, et al.
(författare)
-
Altered basophil function in patients with chronic kidney disease on hemodialysis
- 2017
-
Ingår i: Clinical Nephrology. - : DUSTRI-VERLAG DR KARL FEISTLE. - 0301-0430. ; 88:2, s. 86-96
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: Chronic kidney disease (CKD) leads to impairment of immune cell function. Given the potential role of basophils in the pathogenesis of CKD, we aimed to study the basophil responsiveness towards microbial antigen exposure, judged as adhesion molecule expression and degranulation, in CKD patients on hemodialysis. Materials and methods: We selected markers linked to two crucial biological phases: the transmigration and degranulation processes, respectively. For the transmigration process, we selected the adhesion molecules CD11b, active CD11b epitope, and CD62L and for the degranulation process CD203c (piecemeal degranulation marker), CD63 (degranulation marker), and CD300a (inhibitory marker of degranulation). We measured basophil responsiveness after stimulation of different activation pathways in basophils using lipopolysaccharide (LPS), peptidoglycan (PGN), formyl-methyinoyl-leucyl-phenylalanine (fMLP), and anti-FceRI-ab. Results: The expression of CD63 in basophils following activation by fMLP was significantly higher in the patient group compared to matched healthy controls, but no differences were observed after activation by anti-Fc.RI. CD300a expression was significantly higher in patients following activation by fMLP and anti-Fc.RI, and the active epitope CD11b expression was significantly higher in patients after LPS activation. In addition, we found that CD62L was not shed from the cell surface after activation with LPS and fMLP. A slight downregulation was noted after activation with anti-Fc.RI in healthy controls. Conclusion: Together, these data demonstrate that basophil functions related to adhesion and degranulation are altered in CKD patients on hemodialysis, which indicates a potential role for the basophil in the pathogenesis of complications related to infections.
|
|
| 8. |
- Aljadi, Zenib, et al.
(författare)
-
Microfluidic Immunoaffinity Basophil Activation Test for Point-of-Care Allergy Diagnosis
- 2019
-
Ingår i: Journal of Applied Laboratory Medicine (JALM). - : American Association for Clinical Chemistry. - 2475-7241 .- 2576-9456. ; 4:2, s. 152-163
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The flow cytometry-based basophil activation test (BAT) is used for the diagnosis of allergic response. However, flow cytometry is time-consuming, requiring skilled personnel and cumbersome processing, which has limited its use in the clinic. Here, we introduce a novel microfluidic-based immunoaffinity BAT (miBAT) method. Methods: The microfluidic device, coated with anti-CD203c, was designed to capture basophils directly from whole blood. The captured basophils are activated by anti-FceRI antibody followed by optical detection of CD63 expression (degranulation marker). The device was first characterized using a basophil cell line followed by whole blood experiments. Weevaluated the device with ex vivo stimulation of basophils in whole blood from healthy controls and patients with allergies and compared it with flow cytometry. Results: The microfluidic device was capable of capturing basophils directly from whole blood followed by in vitro activation and quantification of CD63 expression. CD63 expression was significantly higher (P = 0.0002) in on-chip activated basophils compared with nonactivated cells. The difference in CD63 expression on anti-FceRI-activated captured basophils in microfluidic chip was significantly higher (P = 0.03) in patients with allergies compared with healthy controls, and the results were comparable with flow cytometry analysis (P = 0.04). Furthermore, there was no significant difference of CD63% expression in anti-FceRI-activated captured basophils in microfluidic chip compared with flow cytometry. Conclusions: We report on the miBAT. This device is capable of isolating basophils directly from whole blood for on-chip activation and detection. The new miBAT method awaits validation in larger patient populations to assess performance in diagnosis and monitoring of patients with allergies at the point of care.
|
|
| 9. |
- Alm, Erika, et al.
(författare)
-
Introduction
- 2020
-
Ingår i: Pluralistic struggles in gender, sexuality and coloniality. - London, New York : Palgrave Macmillan. - 9783030474324 - 9783030474317 ; , s. 1-18
-
Bokkapitel (refereegranskat)abstract
- The focus of this book is on the many far from predictable transformative political processes on gender, sexuality and coloniality that grow out of the broad range of bodies and actors engaged in politics outside the hegemonic order and in everyday activities. These processes are not conducted by states, governments or transnational nongovernmental organisations; rather, they are examples of politics in-between states, organisations and national imagined communities. In this first chapter we will introduce some of the main themes, regarding these processes we in our joint research programme have worked on over the last couple of years.
|
|
| 10. |
- Alm, Erika, et al.
(författare)
-
Introduction
- 2021
-
Ingår i: Pluralistic Struggles in Gender, Sexuality and Coloniality. - Cham : Palgrave Macmillan. - 9783030474324 ; , s. 1-18
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The focus of this book is on the many far from predictable transformative political processes on gender, sexuality and coloniality that grow out of the broad range of bodies and actors engaged in politics outside the hegemonic order and in everyday activities. These processes are not conducted by states, governments or transnational nongovernmental organisations; rather, they are examples of politics in-between states, organisations and national imagined communities. In this first chapter we will introduce some of the main themes, regarding these processes we in our joint research programme have worked on over the last couple of years.
|
|
| 11. |
- Alm, Erika, 1975, et al.
(författare)
-
Introduction (Pluralistic Struggles in Gender, Sexuality and Coloniality)
- 2021
-
Ingår i: Pluralistic Struggles in Gender, Sexuality and Coloniality. Challenging Swedish Exceptionalism. - London, New York : Palgrave. - 9783030474317 ; , s. 1-18
-
Bokkapitel (refereegranskat)abstract
- The focus of this book is on the many far from predictable transformative political processes on gender, sexuality and coloniality that grow out of the broad range of bodies and actors engaged in politics outside the hegemonic order and in everyday activities. These processes are not conducted by states, governments or transnational nongovernmental organisations; rather, they are examples of politics in-between states, organisations and national imagined communities. In this first chapter we will introduce some of the main themes, regarding these processes we in our joint research programme have worked on over the last couple of years.
|
|
| 12. |
- Almquist, Joachim, et al.
(författare)
-
Model-Based Analysis Reveals a Sustained and Dose-Dependent Acceleration of Wound Healing by VEGF-A mRNA (AZD8601)
- 2020
-
Ingår i: CPT. - : WILEY. - 2163-8306. ; 9:7, s. 384-394
-
Tidskriftsartikel (refereegranskat)abstract
- Intradermal delivery of AZD8601, an mRNA designed to produce vascular endothelial growth factor A (VEGF-A), has previously been shown to accelerate cutaneous wound healing in a murine diabetic model. Here, we develop population pharmacokinetic and pharmacodynamic models aiming to quantify the effect of AZD8601 injections on the dynamics of wound healing. A dataset of 584 open wound area measurements from 131 mice was integrated from 3 independent studies encompassing different doses, dosing timepoints, and number of doses. Evaluation of several candidate models showed that wound healing acceleration is not likely driven directly by time-dependent VEGF-A concentration. Instead, we found that administration of AZD8601 induced a sustained acceleration of wound healing depending on the accumulated dose, with a dose producing 50% of the maximal effect of 92 mu g. Simulations with this model showed that a single dose of 200 mu g AZD8601 can reduce the time to reach 50% wound healing by up to 5 days.
|
|
| 13. |
- Andersson, Kristina, et al.
(författare)
-
Challenges and opportunities with the EU Taxonomy Regulation– with focus on chemical safety and usage in complex products
- 2023
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The use of Policy Lab processes has been growing in Sweden and other countries to accelerate the adaptation of regulations to emerging technologies. Policy Lab facilitates active collaboration between relevant authorities, companies, and stakeholders through interactive and iterative methods based on Design Thinking principles. This approach bridges the gap between the legislative domain responsible for developing regulatory frameworks and the innovative companies that create solutions for emerging markets using new technologies and opportunities. In our study, we applied Policy Lab processes to the EU Taxonomy Regulation to identify challenges and opportunities related to chemical safety and usage for manufacturers of complex products. The EU Taxonomy Regulation, along with its delegated acts, represent a serious effort to establish standardized sustainability reporting within EU. However, it is still in its early stages and lacks maturity. Moreover, certain ambiguities within the regulation currently prevent a comprehensive comparison of companies due to the development of other legislations. Addressing these gaps depends on the future development of, for example, REACH. Our conclusion is that the EU Taxonomy Regulation is part of a larger “movement” that reflects the policymakers’ intentions. This intention also includes increased data sharing at a significantly different level compared to current practices. In the long run, the shift will enable authorities to access the data and develop new legislations. Our specific focus was on the objective of pollution prevention and control regarding the use and presence of hazardous substances listed in Appendix C of the EU Taxonomy Regulation. According to Appendix C, activities must not lead to the manufacture, placing on the market or use of listed substances, whether on their own, in mixture or in articles. Regarding listed substances, reference is made to existing EU legislation that regulates hazardous substances within the EU. The most challenging aspect in Appendix C is point (g), which aims to identify substances, whether alone, in mixtures, or in articles, that meet the criteria set out in Article 57 of REACH but are not yet included in the Candidate list. Our workshops, interviews, and literature review confirmed that the main challenge in meeting the criteria of Appendix C, specifically point (g) is the need to enhance transparency and traceability throughout supply chains. Overcoming these challenges requires addressing barriers, such as the lack of a harmonized regulatory framework across the value chain, the need for faster identification and restriction of hazardous substances, and the reinforcement of stronger enforcement measures. The enabling of full declaration of the hazardous properties and functions of the substances, while considering the balance between information disclosure and protecting trade secrets, would reduce the need for extensive tracking of substance of very high concern along the value chain. To improve communication along the value chain and identify data gaps while protecting trade secrets, workshop participants have proposed the use of a user-friendly interface based on traffic light scenario. This interface would serve as a filter mechanism, allowing product manufacturers to establish specific criteria for material suppliers to respond to. The objective is to enhance communication, establish criteria, and effectively identify data gaps. While the SCIP database ensures accessibility of information on articles containing substances from the Candidate List above 0.1 w/w%, it is limited to hazardous substances on that list. This means that hazardous substances not listed in the Candidate List may not be covered by the database. The EU Commission has proposed the implementation of a digital product passport to enhance information sharing about products and their supply chain, including substances of concern. Our study is conducted under the Mistra SafeChem program, where screening tools for hazard and exposure assessment of substances are currently being developed. These tools aim to provide screening data for direct decision-making based on the Defined Approach (DA). These screening tools have the potential to contribute to filling data gaps during the early design phases of complex products, particularly when screening for multiple material alternatives.
|
|
| 14. |
|
|
| 15. |
- Andersson, Kristina, et al.
(författare)
-
Geostängslade BK4-transporter vid bropassager och på tjälade vägar
- 2023
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Geofenced heavy trucks to protect bridges at crossings allowing higher weight on frozen roads Winter is our friend. When the road body is deep frozen it can handle more weight than during the rest of the year. However, the bridges are not affected by the cold weather, and they are therefore still vulnerable to increased loads. How can we allow increased loads on frozen roads while ensuring protection of the bridges? In this report, we share our insights from a project with the idea of using geofencing to protect the bridges. The geofencing technology ensures that the truck drives at a lower speed over the bridge and the bridge can withstand loads up to 74 tons since decreased speed reduces dynamic loads. If the road keeper can get guarantees that all heavy trucks drive at a low speed over the bridge, heavier traffic can be accommodated. This technology would of course also be beneficial to use across bridges in Europe regardless of the climate. ' The project “Frozen roads and 74 tons”, paid by the Swedish Transport Administration, consisted of three parts. One part was a pilot study during winter 22/23 demonstrating trucks from AB Volvo and Scania loaded with 74 tons using geofencing when the trucks passed over weak bridges. A speed limit, i.e. 50 km/h, was imposed in a zone around each bridge, whose coordinates were stored in the digital map accessible through the trucks’ Fleet Management System. Two different geofencing technologies were tested: on the one hand Scania’s system with “active” geofencing, where the truck was programmed to maintain the allowed speed over the bridge and calculated and implemented this itself (the driver could, however, override this by pushing the gas pedal to the floor); on the other hand AB Volvo’s system with “passive” geofencing, where the driver received a warning message when approaching the zone and would then slow down if necessary. The drivers were interviewed before and after the pilot about their experience. The results from the pilot showed that if the technology is verified, the truck will do the right thing and is on the right road network when the technology is activated. The drivers also liked geofencing. Geofences thus work in practice. The second part of the project was about quantifying the societal benefits of using geofencing. More efficient planning, control and follow-up can lower costs, reduce environmental impact, and increase traffic safety. Calculations in the project show that about 12 percent of timber transports in Norrland use frozen roads. They can benefit from the technology and if the technology is introduced, the industry would make savings of the equivalent of SEK 15 million / year and reduced energy use equivalent to 280 cubic meter diesel. At national level, this corresponds to an energy efficiency potential of 0.12 percent. The third part of the project was about policy and regulation. Can we use the current legislation, or do we need new legislation to scale the use of geofencing across bridges? How can we ensure compliance? How can we share data? How can we handle EU trade barriers? In the report, we have suggestions for policy and legislation to implement the geofencing technology to protect sensitive bridges. Our analysis shows that it is possible with today's regulations for an authority to introduce regulations on geofences. Such rules should preferably be based on functional requirements and a system of self-monitoring.
|
|
| 16. |
- Annerberg, Anna, 1972-
(författare)
-
Gymnasielärares skrivpraktiker : skrivande som professionell handling i en digitaliserad skola
- 2016
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis is to contribute to deeper knowledge about the writing practices of teachers in upper secondary school. Schools are under constant pressure to respond to the needs and expectations of an ever-changing society and political intentions. A major factor in this change which is taking place in schools is digitalization. Another factor is the adoption of new governing principles for schools involving management by goals and results, which brings increased demands for written documentation of teachers' work.In order to describe and problematize this development the thesis is based on a combination of Critical Discourse Analysis and New Literacy (Clark and Ivanič, 1997). The theoretical framework rests upon an understanding of writing as social action and the idea that texts both affect and are affected by the social environment. The empirical study focuses on twelve teachers and their writing practices, analyzed during week-long field visits over three years. The teachers' talk about their writing is used together with analyses of texts and images to investigate parts of teachers' writing which, according to the teachers, are considered complex and problematic.The findings indicate significant differences between the writing practices of the individual teachers, where each teacher has his or her own system of texts fulfilling different purposes. Despite these differences it is still possible to identify recurrent themes in the discursive conditions for teachers' writing: efficiency, reuse, authority, audit, relationships to addressees, and room to maneuver. The study illustrates possible dilemmas for teachers' writing at the intersection of teachers' professional responsibility and demands for accountability.
|
|
| 17. |
- Bergman, Ebba, 1977-, et al.
(författare)
-
The Enterohepatic Disposition of Rosuvastatin in Pigs and The Impact of Concomitant Dosing with Cyclosporine and Gemfibrozil
- 2009
-
Ingår i: Drug Metabolism And Disposition. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0090-9556 .- 1521-009X. ; 37:12, s. 2349-2358
-
Tidskriftsartikel (refereegranskat)abstract
- The hepatobiliary transport and local disposition of rosuvastatin in pig was investigated, along with the impact of concomitant dosing with two known multiple transport inhibitors; cyclosporine and gemfibrozil. 80 mg rosuvastatin was administered as an intrajejunal bolus dose in Treatments I, II and III (TI, TII, and TIII, respectively; n=6 per treatment). Cyclosporine (300 mg) and gemfibrozil (600 mg) were administered in addition to the rosuvastatin dose in TII and TIII, respectively. Cyclosporine was administered as a two hour intravenous infusion and gemfibrozil as an intrajejunal bolus dose. In Treatment IV (TIV, n=4) was 5.9 mg rosuvastatin administered as an intravenous bolus dose. The study was conducted using a pig model, which enabled plasma sampling from the portal (VP), hepatic (VH) and femoral veins and bile from the common hepatic duct. The biliary recovery of the administered rosuvastatin dose was 9.0±3.5% and 35.7±15.6% in TI and TIV, respectively. Rosuvastatin was highly transported into bile as the median AUCbile/AUCVH ratio was 1770 (1640-11300) in TI. Gemfibrozil did not have an effect on the plasma pharmacokinetics of rosuvastatin, most likely because the unbound inhibitor concentrations did not exceed the reported IC50-values. However, cyclosporine significantly reduced the hepatic extraction of rosuvastatin (TI; 0.89±0.06, TII; 0.46±0.13) and increased the AUCVP and AUCVH by 1.6 and 9.1-fold, respectively. In addition, the biliary exposure and fe, bile were reduced by ≈50%. The strong effect of cyclosporine was in accordance with inhibition of sinusoidal uptake transporters, such as members of the OATP-family, rather than canalicular transporters.
|
|
| 18. |
|
|
| 19. |
- Boija, Elisabet, et al.
(författare)
-
Effects of ions and detergents in drug partition chromatography on liposomes
- 2004
-
Ingår i: Journal of chromatography A. - : Elsevier BV. - 0021-9673. ; 1030, s. 273-278
-
Tidskriftsartikel (refereegranskat)abstract
- We have determined drug partitioning into phospholipid bilayers by immobilized-liposome chromatography. Electrostatic effects on the drug partitioning were observed on neutral bilayers at low ionic strength. The size of the counterions affected the partitioning. When liposomes were supplemented with ionic detergents the partitioning of charged drugs was strongly affected, allowing complete separation of drugs of different charges which showed similar retention on neutral bilayers. Partial separation was obtained on bilayers containing fatty acid. Detergent ions or fatty acid inserted into phospholipid bilayers affected the partitioning of drugs much more than did free ions or phospholipid head group charges.
|
|
| 20. |
- Garcia, Luna Prieto, et al.
(författare)
-
Physiologically Based Pharmacokinetic Model of Itraconazole and Two of Its Metabolites to Improve the Predictions and the Mechanistic Understanding of CYP3A4 Drug-Drug Interactions
- 2018
-
Ingår i: Drug Metabolism And Disposition. - : The American Society for Pharmacology and Experimental Therapeutics. - 0090-9556 .- 1521-009X. ; 46:10, s. 1420-1433
-
Tidskriftsartikel (refereegranskat)abstract
- Physiologically based pharmacokinetic (PBPK) modeling for itraconazole using a bottom-up approach is challenging, not only due to complex saturable pharmacokinetics (PK) and the presence of three metabolites exhibiting CYP3A4 inhibition, but also because of discrepancies in reported in vitro data. The overall objective of this study is to provide a comprehensive mechanistic PBPK model for itraconazole in order to increase the confidence in its drug-drug interaction (DDI) predictions. To achieve this, key in vitro and in vivo data for itraconazole and its major metabolites were generated. These data were crucial to developing a novel bottom-up PBPK model in Simcyp (Simcyp Ltd., Certara, Sheffield, United Kingdom) for itraconazole and two of its major metabolites: hydroxy-itraconazole (OH-ITZ) and keto-itraconazole (keto-ITZ). Performance of the model was validated using prespecified acceptance criteria against different dosing regimens, formulations for 29 PK, and DDI studies with midazolam and other CYP3A4 substrates. The main outcome is an accurate PBPK model that simultaneously predicts the PK profiles of itraconazole, OH-ITZ, and keto-ITZ. In addition, itraconazole DDIs with midazolam and other CYP3A4 substrates were successfully predicted within a 2-fold error. Prediction precision and bias of DDI expressed as geometric mean fold error were for the area under the concentration-time curve and peak concentration, 1.06 and 0.96, respectively. To conclude, in this paper a comprehensive data set for itraconazole and its metabolites is provided that enables bottom-up mechanism-based PBPK modeling. The presented model is applicable for studying the contribution from the metabolites and allows improved assessments of itraconazole DDI.
|
|
| 21. |
|
|
| 22. |
- Gustafsson, Anna W, et al.
(författare)
-
Bedömningspraktiker, språkbruk och likvärdighet
- 2021. - 1
-
Ingår i: Hållbar bedömning: bildning, välbefinnande och utveckling i skolans bedömningsarbete. - 9789127827301 ; , s. 338-356
-
Bokkapitel (populärvet., debatt m.m.)
|
|
| 23. |
- Houmann, Anna, et al.
(författare)
-
Electronical digital instrument (EDI) - Digital music making with children, youth and music teacher students
- 2023
-
Ingår i: ; , s. 61-61
-
Konferensbidrag (refereegranskat)abstract
- Making music with digital tools might be considered common knowledge in music education. However, there are vast numbers of music teachers who feel insecure when it comes to actually using it as a prominent tool for music making in their classrooms. The objective of this workshop is to show how students of different ages together with their music teachers create, produce and perform music by EDI. The EDI is a system based on three components: 1) A computer 2) User-configured software (ex Ableton Live) 3) Performance controllers with grid, keyboard, and mix control capabilities (ex Ableton Push). This work lecture includes presentations, cases and examples on digital music making brought in by students and music teachers. Via this interaction participants will experience real time collaborative music making, producing and performing with EDI and take part of the result.All four presenters are part of the practice based project "The digital student - computer as instrument in school" and will through the workshop format highlight some of its essential findings. This work lecture will display a number of ways these digital tools can help music teachers take advantage of students’ resourcefulness and creativity to work collaboratively and individually in their music making. The aims of this work lecture are to give the participants the opportunity to:• Experience digital music making through given tools to create and produce music• Give inspiration to implement and/or develop new ways of using digital tools in making and producing music, in music education• Open up a broader view on the computer as students main instrument in music education• Understand how digital tools in making, producing and performing music highlights and emphasize students voices in the process as well as in the result
|
|
| 24. |
- Houmann, Anna, et al.
(författare)
-
The Digital Student - challenges and opportunities using the computer as main instrument in music education in Sweden
- 2023
-
Konferensbidrag (refereegranskat)abstract
- Teachers in the aesthetic program in upper secondary school in Sweden have identified that there are great opportunities and challenges in teaching and working with students who have EDI as their main instrument. From a student perspective it has relevance to being part of meaningful music education developing their musical identity. Students playing EDI can explore an array of electronical musical styles and develop high-level techniques using their unique electronic music system configuration. This research project aims to generate knowledge about what teaching about and in EDI means for teachers and students in the aesthetic programs as well as teachers and students in the music teacher training. In this full-scale research project university researchers collaborate with teachers in upper secondary school, teachers and teacher students in teacher education in developing both scientific knowledge and EDI teaching guidelines. The project is relevant both from a professional and research perspective as there are relatively few studies and little knowledge of EDI as part of music teaching. However, there are parallels drawn from the related research field music technology (King, Himonides & Ruthmann, 2017). The design of the study is based on Educational Design Research (McKenney & Reeves, 2012), meaning that the teaching and its outcomes are examined and analyzed through a number of iterative cycles. Interventions in classrooms are combined with interviews, music labs, regular meetings in the collaborative research group for analysis of teaching, methodological discussions and processing of relevant research and teaching material. The project has not only generated a scientific understanding of what EDI means in the current context, but also contributed to the development of concrete teaching models based on research and proven experience with relevance to the school system, teacher training and the research community. Presenters are university researchers and teachers in addition to teachers in upper secondary school.
|
|
| 25. |
- Johnsson Harrie, Anna, 1972-
(författare)
-
Staten och läromedlen : En studie av den svenska statliga förhandsgranskningen av läromedel 1938-1991
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Studien handlar om statlig påverkan på skolans läromedel. Här studeras såväl de politiska besluten om, som det konkreta genomförandet av, den svenska statliga förhandsgranskningen av läromedel, från starten 1938 till avskaffandet 1991. De politiska besluten och genomförandet sker på skilda arenor. Med hjälp av teoretiska begrepp från såväl läroplansteori som statsvetenskaplig implemen-teringsteori synliggörs och analyseras de olika arenorna samt relationerna mellan dem. Den politiska debatten studeras genom det offentliga trycket. Studien visar att granskningen infördes i politisk enighet och avskaffades helt utan politisk debatt. De politiska argumenten för granskning har varit att hålla priserna på läroböcker nere samt säkra läromedlens kvalitet. Vad som avsågs med kvalitet har dock varierat mellan olika aktörer och över tid. När det gäller genomförandet av granskningen studeras både Läroboks-/Läromedelsnämndens instruktioner till granskarna, och granskarnas utlåtanden om läromedel i samhällskunskap för gymnasieskolan. Den reella granskningen hade ofta fokus på att söka sakfel i läromedlen. Under 1970-talet fick objektivitetsfrågor genomslag i granskningen. Läroplanen, som betonades på den politiska arenan, användes dock i mindre utsträckning i det reella genomförandet av granskningen. Styrningsresultatet var beroende av aktörerna på realiseringsarenan och deras förståelse, vilja och kunnande. Styrningen kunde dock, i vissa fall, nå ända fram och påverka lärobokstexten. I dessa fall fanns en fungerande styrning från politisk debatt, via lagtext och granskning till en förändrad läromedelstext.
|
|
| 26. |
- Kalm, Frida, et al.
(författare)
-
Adhesion molecule cross-linking and cytokine exposure modulate IgE- and non-IgE-dependent basophil activation
- 2021
-
Ingår i: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 162:1, s. 92-104
-
Tidskriftsartikel (refereegranskat)abstract
- Basophils are known for their role in allergic inflammation, which makes them suitable targets in allergy diagnostics such as the basophil activation test (BAT) and the microfluidic immunoaffinity basophil activation test (miBAT). Beside their role in allergy, basophils have an immune modulatory role in both innate immunity and adaptive immunity. To accomplish this mission, basophils depend on the capability to migrate from blood to extravascular tissues, which includes interactions with endothelial cells, extracellular matrix and soluble mediators. Their receptor repertoire is well known, but less is known how these receptor–ligand interactions impact the degranulation process and the responsiveness to subsequent activation. As the consequences of these interactions are crucial to fully appreciate the role of basophils in immune modulation and to enable optimization of the miBAT, we explored how basophil activation status is regulated by cytokines and cross-linking of adhesion molecules. The expression of adhesion molecules and activation markers on basophils from healthy blood donors was analysed by flow cytometry. Cross-linking of CD203c, CD62L, CD11b and CD49d induced a significant upregulation of CD63 and CD203c. To mimic in vivo conditions, valid also for miBAT, CD62L and CD49d were cross-linked followed by IgE-dependent activation (anti-IgE), which caused a reduced CD63 expression compared with anti-IgE activation only. IL-3 and IL-33 priming caused increased CD63 expression after IgE-independent activation (fMLP). Together, our data suggest that mechanisms operational both in the microfluidic chip and in vivo during basophil adhesion may impact basophil anaphylactic and piecemeal degranulation procedures and hence their immune regulatory function.
|
|
| 27. |
|
|
| 28. |
- Kalm, Frida, et al.
(författare)
-
Development and clinical testing of a microfluidic immunoaffinity basophil activation test for point-of-care allergy diagnosis
- 2019
-
Ingår i: 23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019. - : Chemical and Biological Microsystems Society. ; , s. 657-658
-
Konferensbidrag (refereegranskat)abstract
- The Basophil Activation Test (BAT) is a valuable allergy diagnostic tool but is time-consuming and requires skilled personnel, which has limited its clinical use. We therefore developed and clinically tested a microfluidic immunoaffinity BAT (miBAT) technique where we captured basophils directly from whole blood followed by in vitro activation and quantification of activation markers. For the first time basophils captured from whole blood, from both allergic patients and healthy donors, have been activated using allergens.
|
|
| 29. |
- Lundahl, Anna, et al.
(författare)
-
High-resolution mass spectrometric investigation of the phase I and II metabolites of finasteride in pig plasma, urine and bile
- 2014
-
Ingår i: Xenobiotica. - : Informa UK Limited. - 0049-8254 .- 1366-5928. ; 44:6, s. 498-510
-
Tidskriftsartikel (refereegranskat)abstract
- 1. The metabolite profile of the 5 alpha-reductase type II inhibitor finasteride has been studied in pig plasma, urine and bile using high-resolution mass spectrometry. The porcine biotransformation products were compared to those formed by human liver microsomes and to literature data of recently identified human in vivo metabolites. The objective of this study was to gain further evidence for the validity of using pigs for advanced, invasive drug-drug interaction studies that are not possible to perform in humans. 2. The use of high-resolution mass spectrometry with accurate mass measurements enabled identification of the metabolites by calculation of their elemental compositions as well as their fragmentation patterns. 3. There was an excellent match between the porcine and human metabolic profiles, corroborating the pig as a model of human drug metabolism. The glucuronides of the two recently described human hydroxylated metabolites MX and MY and the carboxylated metabolite M3 were identified as the major biotransformation products of finasteride in pig urine and bile. 4. Furthermore, the CYP enzymes involved in the formation of the hydroxylated metabolites were characterized. Human recombinant CYP3A4 could produce the two major hydroxylated metabolites MX and MY, whereas human recombinant CYP2D6 formed MY only.
|
|
| 30. |
- Lundahl, Anna, et al.
(författare)
-
Identification of Finasteride Metabolites in Human Bile and Urine by High-Performance Liquid Chromatography/Tandem Mass Spectrometry
- 2009
-
Ingår i: Drug Metabolism And Disposition. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0090-9556 .- 1521-009X. ; 37:10, s. 2008-2017
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to further investigate the metabolism of the 5α-reductase inhibitor, finasteride, and to identify previously unknown phase I and phase II metabolites in vitro and in vivo in human bile and urine. Healthy volunteers were given 5 mg of finasteride, directly to the intestine, and bile and urine were collected for 3 and 24 h, respectively. A single-pass perfusion technique, Loc-I-Gut, was used for drug administration and bile collection from the proximal jejunum, distal to papilla of Vater. Incubations with human liver microsomes/S9 fractions and different cofactors were performed with finasteride and the previously known metabolites, ω-hydroxy finasteride (M1) and finasteride-ω-oic acid (M3). Liquid chromatography coupled to triple quadrupole mass spectrometry (MS) with positive/negative electrospray ionization and ion trap with MSn measurements were used for structural investigations and identification of metabolites. Two hydroxy metabolites of finasteride, other than M1, and one intact hydroxy finasteride glucuronide were identified in vitro and in bile and urine. The glucuronide and at least one of the hydroxy metabolites were previously unidentified. M1 and M3 were glucuronidated in vitro by specific human UDP-glucuronosyltransferases, UGT1A4 and UGT1A3, respectively. M1 glucuronide was not identified in vivo, and M3 glucuronide, an acyl glucuronide, was present in low amounts in bile from a few individuals. In conclusion, previously undescribed metabolites were identified, in vitro and in human urine and bile. Bile collection using the Loc-I-Gut technique followed by sensitive mass spectrometry analysis led to the discovery of novel, both phase I and phase II, finasteride metabolites in human bile.
|
|
| 31. |
- Lundahl, Anna, et al.
(författare)
-
In Vivo Investigation in Pigs of Intestinal Absorption, Hepatobiliary Disposition, and Metabolism of the 5 alpha-Reductase Inhibitor Finasteride and the Effects of Coadministered Ketoconazole
- 2011
-
Ingår i: Drug Metabolism And Disposition. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0090-9556 .- 1521-009X. ; 39:5, s. 847-857
-
Tidskriftsartikel (refereegranskat)abstract
- The overall aim of this detailed investigation of finasteride's pharmacokinetics (PK) and metabolism in pigs was to improve the understanding of the in vivo PK for this drug and its metabolites. Specific aims were to examine the effects of ketoconazole co-administration on the PK in three plasma compartments (the portal, hepatic and femoral veins), bile and urine and to utilize these data to in detail study the intestinal absorption, the liver extraction ratio and apply a semi-physiological based PK model to the data. The pigs received an intrajejunal dose of finasteride (0.8 mg/kg) either alone (n=5) or together with ketoconazole (10 mg/kg) (n=5), or an intravenous dose (0.2 mg/kg) (n=3). Plasma, bile and urine (collected from 0-6 hours) were analyzed with ultra performance liquid chromatography tandem mass spectrometry. Ketoconazole increased the bioavailability of finasteride from 0.36±0.23 to 0.91±0.1 (p<0.05) and the terminal half-life from 1.6±0.4 to 4.0±1.1 hours (p<0.05). From deconvolution it was found that the absorption rate from the intestine to the portal vein was rapid and the product of the fraction absorbed and the fraction that escaped gut wall metabolism was high (fa*FG≈1). Interestingly, the apparent absorption rate constant (k(a)) to the femoral vein was lower compared to the portal vein, probably because of binding and distribution within the liver. The liver extraction ratio was time-dependent and varied with the two routes of administration. After intrajejunal administration, from 1 6 hours the liver extraction ratio was significantly (p<0.05) reduced by the ketoconazole treatment from intermediate (0.41±0.21) to low (0.21±0.10).
|
|
| 32. |
- Lundahl, Anna, 1980-
(författare)
-
In vivo Pharmacokinetic Interactions of Finasteride and Identification of Novel Metabolites
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The general aim of this thesis was to improve the understanding of the in vivo pharmacokinetics and, in particular, the metabolism of finasteride, a 5α-reductase inhibitor used in the treatment of enlarged prostate glands and male pattern baldness. CYP3A4 has been identified as the major enzyme involved in the sequential metabolism of finasteride to ω-OH finasteride (M1) and ω-COOH finasteride (M3). The consequences of induced and inhibited metabolism on the pharmacokinetics of finasteride and its metabolites were investigated in humans and pigs. Both studies included bile collection. The collected human and pig samples were used for the metabolite identification. As expected, induced metabolism led to reduced plasma exposure of finasteride and inhibited metabolism had the opposite effect. The interactions were investigated in detail and included examination of the biliary pharmacokinetics of finasteride and its metabolites. In pigs, the study included monitoring of the hepatic extraction over time, deconvolution and the development of a semi-physiological model for comparison of the effects on the gut wall and liver metabolism. For M3, the concentration ratios of bile to plasma and the renal clearance indicated that carrier-mediated processes are involved in the biliary and urinary excretion. This was not, however, the case for finasteride. The metabolite, M1, could not be quantified either in humans or pigs. Instead, two other OH metabolites, M1 isomers, were identified in humans. These metabolites were found to undergo glucuronide conjugation. In humans, one glucuronide was identified intact and in pigs, both glucuronides were identified intact in bile and in urine. In addition, a glucuronide of M3 was identified in human bile. In conclusion, advances have been made in the understanding of the pharmacokinetics of finasteride, in particular in relation to the metabolism. Hopefully, the findings of this comprehensive investigation can be applied to other drugs and novel chemical entities.
|
|
| 33. |
- Lundahl, Anna, et al.
(författare)
-
The effect of St. John's wort on the pharmacokinetics, metabolism and biliary excretion of finasteride and its metabolites in healthy men
- 2009
-
Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 36:4-5, s. 433-443
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate what the consequences of induced drug metabolism, caused by St. John's wort (SJW, Hypericum perforatum) treatment, would have on the plasma, biliary and urinary pharmacokinetics of finasteride and its two previously identified phase I metabolites (hydroxy-finasteride and carboxy-finasteride). Twelve healthy men were administered 5mg finasteride directly to the intestine via a catheter with a multi-channel tubing system, Loc-I-Gut, before and after 14 days SJW (300mg b.i.d, hyperforin 4%) treatment. Bile samples were withdrawn via the Loc-I-Gut device from the proximal jejunum. LC-ESI-MS/MS was used to analyze finasteride and its metabolites in plasma, bile and urine. HPLC-UV was used to analyze hyperforin in plasma. The herbal treatment significantly reduced the peak plasma concentration (C(max)), the area under the plasma concentration-time curve (AUC(0-24h)) and the elimination half-life (t(1/2)) of finasteride. The geometric mean ratios (90% CI) were 0.42 (0.36-0.49), 0.66 (0.56-0.79) and 0.54 (0.48-0.61), respectively. Finasteride was excreted unchanged to a minor extent into bile and urine. Hydroxy-finasteride was not detected in plasma, bile or urine. Carboxy-finasteride was quantified in all three compartments and its plasma pharmacokinetics was significantly affected by SJW treatment. Hyperforin concentration in plasma was 21+/-7ng/ml approximately 12h after the last dose of the 14 days SJW treatment. In conclusion, SJW treatment for 2 weeks induced the metabolism of finasteride and caused a reduced plasma exposure of the drug. New knowledge was gained about the biliary and urinary excretion or the drug and its metabolites.
|
|
| 34. |
- Lundahl, Anna, et al.
(författare)
-
Waste Fibre Reinforced Ecocomposites
- 2010
-
Ingår i: Materials Science Forum. - : Trans Tech Publications. - 0255-5476 .- 1662-9752. ; 636-637, s. 1415-1420
-
Tidskriftsartikel (refereegranskat)abstract
- With a significant production of waste fibrous material, textile companies are now looking for applications where waste materials could be an added-value material. One viable application of these waste materials is in the combination with polymeric matrices, producing composite materials with interesting properties for specific applications, from furniture to thermal and acoustic insulations. The aim of this work was to study the physical and mechanical properties of waste fibre reinforced composites and the influence of different parameters on their mechanical behaviour. Results show that a wide range of different properties and performances may be designed by altering various production parameters, such as thickness of the nonwovens used, time and temperature of the compression moulding, relationship between fibre/matrix ratio, polymeric film used and number of layers.
|
|
| 35. |
|
|
| 36. |
- Lundquist, Anna, et al.
(författare)
-
Interactions of drugs and an oligonucleotide with charged membranes analyzed by immobilized liposome chromatography
- 2006
-
Ingår i: Biomedical Chromatography. - : Wiley. - 0269-3879 .- 1099-0801. ; 20, s. 83-87
-
Tidskriftsartikel (refereegranskat)abstract
- We studied the effect of charged lipids or detergent on the retention of drugs and an oligonucleotide by immobilized liposome chromatography to characterize solute-membrane interactions. This is a novel approach in analysis of oligonucleotide-liposome interactions. The charged lipids (phosphatidylserine or distearoyltrimethylammoniumpropane) or detergent (sodium dodecylsulfate) interacted electrostatically in a concentration-dependent matter with the solutes. The oligonucleotide ions presumably bound to the liposomes by multipoint interactions, which was saturable. Sodium dodecylsulfate seemed to affect the drug-membrane interactions more strongly than phosphatidylserine did, probably due to different positioning in the bilayer.
|
|
| 37. |
|
|
| 38. |
- Malaga, Katarina, et al.
(författare)
-
Tekniska textilier i betong
- 2010
-
Ingår i: CBI-nytt. - 0349-2060. ; :2, s. 2-3
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 39. |
|
|
| 40. |
- Matsson, Elin, et al.
(författare)
-
Effects of ketoconazole on the in vivo biotransformation and hepatobiliary transport of the thrombin inhibitor AZD0837 in pigs
- 2011
-
Ingår i: Drug Metabolism And Disposition. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0090-9556 .- 1521-009X. ; 39:2, s. 239-246
-
Tidskriftsartikel (refereegranskat)abstract
- Ketoconazole has been shown in clinical trials to increase the plasma exposure of the oral anticoagulant prodrug AZD0837 [(2S)-N-{4- [(Z)-amino(methoxyimino)methyl]benzyl}-1-{(2R)-2-[3-chloro-5-(difluoromethoxy)phenyl]-2-hydroxyethanoyl}-azetidine-2-carboxamide] and its active metabolite, AR-H067637 [(2S)-N-{4-[amino(imino)methyl]benzyl}-1-{(2R)-2-[3-chloro-5-(difluoromethoxy)phenyl]-2-hydroxyethanoyl}-azetidine-2-carboxamide]. To investigate the biotransformation of AZD0837 and the effect of ketoconazole on this process, we used an experimental model in pigs that allows repeated sampling from three blood vessels, the bile duct, and a perfused intestinal segment. The pigs received AZD0837 (500 mg) given enterally either alone (n = 5) or together with single-dose ketoconazole (600 mg) (n = 6). The prodrug (n = 2) and its active metabolite (n = 2) were also administered intravenously to provide reference doses. The plasma data revealed considerable interindividual variation in the exposure of the prodrug, intermediate metabolite, and active metabolite. However, AR-H067637 was detected at very high concentrations in the bile with low variability (Ae(bile) = 53 ± 6% of the enteral dose), showing that the compound had indeed been formed in all of the animals and efficiently transported into the bile canaliculi. Concomitant dosing with ketoconazole increased the area under the plasma concentration-time curve for AZD0837 (by 99%) and for AR-H067637 (by 51%). The effect on the prodrug most likely arose from inhibited CYP3A-mediated metabolism. Reduced metabolism also seemed to explain the increased plasma exposure of the active compound because ketoconazole prolonged the terminal half-life with no apparent effect on the extensive biliary excretion and biliary clearance. These in vivo results were supported by in vitro depletion experiments for AR-H067637 in pig liver microsomes with and without the addition of ketoconazole.
|
|
| 41. |
- Müller, Jan-Hendrik, et al.
(författare)
-
Navigating the Future: Enhancing E-Scooter Traffic Management through Governance and Regulation
- 2024
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The GeoSence project, which is part of the Joint Programme Initiative (JPI) Urban Europe, aims to provide an overview of the current state of the art and showcase practical applications of geofencing. The project partners come from Germany, Norway, Sweden, and the UK and is funded by the European Union's Horizon 2020 programme under the ERA-NET Cofound Urban Accessibility and Connectivity. Geofencing is defined as a virtual boundary in a specific geographical location, either fixed or dynamic. The GeoSence project focuses on improving urban transport by using geofencing methods for traffic planning and management. In this report, we examine the policies that support these solutions, while also identifying barriers and opportunities for smarter regulation. Our research focuses primarily on Munich, looking at issues such as parking, restricted areas, and data collection from e-scooter operators. Many European cities are struggling with problems associated with e-scooters, such as dangerous driving and inappropriate parking. In Munich, geofencing technology has been tested as a solution to address these issues and improve road safety, particularly for pedestrians. The city's main objective was to improve road safety for all road users, especially pedestrians. By reducing inappropriate parking, the city also expected to increase public acceptance of e-scooters. As a first step in dealing with this new form of mobility, the city's initial response included the creation of 30 dedicated parking zones in 2020 and 2021 and a voluntary commitment with mobility service providers to regulate this new form of mobility. By joining the GeoSence project, the city wanted to explore geofencing as a solution to the persistent road safety problems caused mainly by poorly parked e-scooters. With GeoSence, Munich was able to monitor and optimise the use of parking zones, improve parking and road safety, and prevent drunk driving. To define the case studies, the city collected data from e-scooter operators, including parking start and end times, vehicle types and GPS coordinates. This data was used to identify parking hotspots and plan further parking infrastructure, as well as to evaluate the use of existing parking infrastructure. Three different case studies were conducted to evaluate new parking policies based on geofencing. The first case study focused on parking e-scooters in 43 dedicated zones in Munich's old town. The second focused on the optimisation of parking in 30 existing zones outside the historic centre of the old town of Munich. Finally, the third case study introduced a new parking concept for the Oktoberfest events in 2022 and 2023. This temporary concept included designated zones and time-based usage restrictions. The results showed an increased concentration of e-scooters in the designated zones, improving the parking situation. Since GeoSence has demonstrated the success of the measures to improve the parking of e-scooters across the city, in November 2023 the City Council also mandated the Department of Mobility and the Department of Construction to create a citywide network of parking zones for shared micro-mobility services by 2026. This will build on the experience of the pilot concept for such parking facilities in the old town. In cooperation with mobility providers, no-parking zones of 100 metres will be set up around each parking space. The municipality is also working on a concept to manage the use of electric scooters during major events. To monitor compliance, geofencing tools will continue to collect data, while the results of GeoSence will be used to develop smart policies. The city's own MDAS project will provide dedicated monitoring data and analysis to make the implementation of the new parking zones and policies more effective. In the GeoSence project, the city of Munich combined contracts, public procurement, and regulation. The city entered into voluntary data-sharing agreements with operators, procured a data-sharing platform, and then used the data for better and smarter regulation. Better and smarter regulation is about moving away from a linear sequence of independent steps to a cycle of interlinked, mutually reinforcing steps. The idea is that regulation will be more effective and that citizens will have a better understanding of the rules and be more involved in creating new rules. We live in an ever-changing world, and with better and smarter regulation, our society will adapt more easily to new technologies. Rules also need to be future-proof and resilient, so that our society can adapt if necessary. Rules must also not hamper technological development and innovation. Better and smarter regulation also means making rules easier to understand and reducing administrative burdens for citizens and businesses. To achieve regulatory coherence and coordination, it's important for countries and cities to share their experiences. E-scooter regulations vary across the EU, with Swedish cities having the ability to regulate speed while German cities do not. Munich is leading the way in improving regulatory practices through geofencing, which helps build capacity and competence. In the case study regarding the use of e-scooters during the Oktoberfest, Munich demonstrated its dynamic and responsive regulation by adapting rules to human behaviour and using a risk-based approach. Geofencing is proving to be essential in the development of adaptive and informed regulation. Effective regulation also requires collaboration with stakeholders and the collection of robust, high-quality data. Munich's transition to evidence-based and smart regulation involved building trust with e-scooter operators and investing in a data platform. The city recognises the importance of training staff and involving stakeholders in transparent regulatory processes. Future challenges include ensuring public participation in data-driven decision-making and continuously evaluating and improving the regulatory framework. Geofencing is therefore proving to be essential in developing adaptive and informed regulation.
|
|
| 42. |
-
Pluralistic Struggles in Gender, Sexuality and Coloniality. Challenging Swedish Exceptionalism
- 2021
-
Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- “There is a hegemonic narrative of Sweden as an exemplary and exceptional feminist nation-state, one that exists in a secular, migrant-friendly, and market-friendly, liberal democracy. Yet this narrative’s racial and religious exclusions and conflicts – of which there are many – have led feminists and LGBTQ activists to question the terms of normative belonging, and to probe the tensions and frictions of contemporary Sweden. This necessary and powerful collection of essays reveals both the exclusions of this exceptionalist national narrative, one that the editors and authors trenchantly term ‘neocolonial,’ and the demands of feminist, queer and trans artists, researchers, migrants, and activists striving to produce lives that think a different Sweden: of communities that are plural, transnational, multi-racial, transformative, radical and ever-changing.” — Inderpal Grewal, Professor Emerita, Yale University, USA
|
|
| 43. |
- Tallberg Broman, Ingegerd, et al.
(författare)
-
Genusperspektiv på förskola, skola och utbildning : Några inlägg från en arbetsgrupp på lärarutbildningen
- 2002
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Baksidestext: Var står genusperspektiv idag och vilka frågor är högljudda och aktuella? Är genusperspektiv, liksom andra perspektiv, beroende av enstaka entusiaster, och är det en ren tillfällighet om de studerande möter genusperspektiv i utbildningen? Hur ser skolans vardag ut i ett genusperspektiv? Varför är det så angeläget att få fler män till skolan? Hur ser pedagogernas föreställningar om barn och genus ut? Handlar det om självständiga flickor och behövande pojkar? Flickor med förnuft och pojkar med kropp? Hur ser killarna på yrkesprogrammen på sin situation? Hur tänker högstadieflickor och pojkar om NO? Kan genusperspektiv innebära att synliggöra det osynliggjorda? Vad händer med alla ambitioner i detta område när man går från utbildningstid till klassrummet? Detta är några frågor som tas upp i denna rapport. Nio författare, varav två nyblivna lärare och sju lärarutbildare, sammanfattar här några av sina erfarenheter och väcker frågor utifrån genusperspektiv på förskolans och skolans praktik och teori.
|
|
| 44. |
- Wlodarczyk, Mark T., et al.
(författare)
-
Tänk Om : Stadsrumsvisioner För Norrköping
- 1995
-
Rapport (populärvet., debatt m.m.)abstract
- Studierna har koncentrerats på tre problemzoner i det angivna snittet, nämligen varuhuskvarterens ovårdade block, parkeringskvarterens ödemarker och de nya bostadskvarterens oklara blandning av buskar och bilar. Möjligheterna i dessa tre zoner har utvecklats och bearbetats individuellt och i grupp, i projekt och riktlinjer.
|
|
| 45. |
- Öhman, Anna, 1962-
(författare)
-
Återkoppling i interaktion : En studie av klassrumsbaserad bedömning i frisörutbildningen
- 2017
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present dissertation concerns social organization of feedback in ongoing hairdressing education. The central aim is to explore feedback between teacher and student in multimodal interaction within classroom assessment, as co-production of action and student’s participation. Classroom assessment and feedback are understood as social actions situated in interaction.The empirical data consists of video recordings from two vocational schools. From 31 hours of video material, selections of feedback interactions were made. At first, teacher and student communication in feedback cycles and loops was analysed from a social semiotic perspective. Secondly, examples of student initiated feedback loops were analysed from a conversation analytic perspective. Thirdly, a single case of a teacher and a student interacting through feedback related to creative subject content was analysed from a conversation analytic perspective. The analyses show the importance of collaborative use of artefacts and embodied communication in the production of mutual understanding; opening for student initiatives in actions of assessment as well as feedback. Silence and body position were found to be important resources giving the student space to display concern. Participation in feedback practices within creative subject content emerged in a trajectory of problem detection to problem solving, resulting in tacit dimensions of hairdressers’ knowing made explicit.The findings indicate the importance of taking a participatory perspective on multimodal interaction when exploring actions of assessment and feedback between teacher and student. This study shows how feedback is not only given from the teacher, but also locally produced as a collaborative practice between teachers and students, displaying tacit dimensions of professional knowledge and subject content.
|
|
