| 1. |
- Eriksson, Olof, et al.
(författare)
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Species differences in pancreatic binding of DO3A-VS-Cys40-Exendin4
- 2017
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 54:11, s. 1039-1045
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Radiolabeled Exendin-4 has been proposed as suitable imaging marker for pancreatic beta cell mass quantification mediated by Glucagon-like peptide-1 receptor (GLP-1R). However, noticeable species variations in basal pancreatic uptake as well as uptake reduction degree due to selective beta cell ablation were observed.METHODS: -Exendin4 Positron Emission Tomography (PET) in the same species. In vitro, ex vivo, and in vivo data formed the basis for calculating the theoretical in vivo contribution of each pancreatic compartment.RESULTS: -Exendin4.CONCLUSIONS: IPR as well as the exocrine GLP-1R density is the main determinants of the species variability in pancreatic uptake. Thus, the IPR in human is an important factor for assessing the potential of GLP-1R as an imaging biomarker for pancreatic beta cells.
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| 2. |
- Eriksson, Ulf G, et al.
(författare)
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Pharmacokinetics of melagatran and the effect on ex vivo coagulation time in orthopaedic surgery patients receiving subcutaneous melagatran and oral ximelagatran : a population model analysis
- 2003
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Ingår i: Clinical Pharmacokinetics. - 0312-5963 .- 1179-1926. ; 42:7, s. 687-701
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVE: Ximelagatran, an oral direct thrombin inhibitor, is rapidly bioconverted to melagatran, its active form. The objective of this population analysis was to characterise the pharmacokinetics of melagatran and its effect on activated partial thromboplastin time (APTT), an ex vivo measure of coagulation time, in orthopaedic surgery patients sequentially receiving subcutaneous melagatran and oral ximelagatran as prophylaxis for venous thromboembolism. To support the design of a pivotal dose-finding study, the impact of individualised dosage based on bodyweight and calculated creatinine clearance was examined. DESIGN AND METHODS: Pooled data obtained in three small dose-guiding studies were analysed. The patients received twice-daily administration, with either subcutaneous melagatran alone or a sequential regimen of subcutaneous melagatran followed by oral ximelagatran, for 8-11 days starting just before initiation of surgery. Nonlinear mixed-effects modelling was used to evaluate rich data of melagatran pharmacokinetics (3326 observations) and the pharmacodynamic effect on APTT (2319 observations) in samples from 216 patients collected in the three dose-guiding trials. The pharmacokinetic and pharmacodynamic models were validated using sparse data collected in a subgroup of 319 patients enrolled in the pivotal dose-finding trial. The impact of individualised dosage on pharmacokinetic and pharmacodynamic variability was evaluated by simulations of the pharmacokinetic-pharmacodynamic model. RESULTS: The pharmacokinetics of melagatran were well described by a one-compartment model with first-order absorption after both subcutaneous melagatran and oral ximelagatran. Melagatran clearance was correlated with renal function, assessed as calculated creatinine clearance. The median population clearance (creatinine clearance 70 mL/min) was 5.3 and 22.9 L/h for the subcutaneous and oral formulations, respectively. The bioavailability of melagatran after oral ximelagatran relative to subcutaneous melagatran was 23%. The volume of distribution was influenced by bodyweight. For a patient with a bodyweight of 75kg, the median population estimates were 15.5 and 159L for the subcutaneous and oral formulations, respectively. The relationship between APTT and melagatran plasma concentration was well described by a power function, with a steeper slope during and early after surgery but no influence by any covariates. Simulations demonstrated that individualised dosage based on creatinine clearance or bodyweight had no clinically relevant impact on the variability in melagatran pharmacokinetics or on the effect on APTT. CONCLUSIONS: The relatively low impact of individualised dosage on the pharmacokinetic and pharmacodynamic variability of melagatran supported the use of a fixed-dose regimen in the studied population of orthopaedic surgery patients, including those with mild to moderate renal impairment.
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| 3. |
- Ganguly, Koustav, et al.
(författare)
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Computational modeling of lung deposition of inhaled particles in chronic obstructive pulmonary disease (COPD) patients : identification of gaps in knowledge and data
- 2019
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Ingår i: Critical reviews in toxicology. - : TAYLOR & FRANCIS LTD. - 1040-8444 .- 1547-6898. ; 49:2, s. 160-173
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Forskningsöversikt (refereegranskat)abstract
- Computational modeling together with experimental data are essential to assess the risk for particulate matter mediated lung toxicity and to predict the efficacy, safety and fate of aerosolized drug molecules used in inhalation therapy. In silico models are widely used to understand the deposition, distribution, and clearance of inhaled particles and aerosols in the human lung. Exacerbations of chronic obstructive pulmonary disease (COPD) have been reported due to increased particulate matter related air pollution episodes. Considering the profound functional, anatomical and structural changes occurring in COPD lungs, the relevance of the existing in silico models for mimicking diseased lungs warrants reevaluation. Currently available computational modeling tools were developed for the healthy adult (male) lung. Here, we analyze the major alterations occurring in the airway structure, anatomy and pulmonary function in the COPD lung, as compared to the healthy lung. We also scrutinize the various physiological and particle characteristics that influence particle deposition, distribution and clearance in the lung. The aim of this review is to evaluate the availability of the fundamental knowledge and data required for modeling particle deposition in a COPD lung departing from the existing healthy lung models. The extent to which COPD pathophysiology may affect aerosol deposition depends on the relative contribution of several factors such as altered lung structure and function, bronchoconstriction, emphysema, loss of elastic recoil, altered breathing pattern and altered liquid volumes that warrant consideration while developing physiologically relevant in silico models.
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| 4. |
- Johansson, Ann-Sofie, 1967-, et al.
(författare)
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Germ line insertions of moloney murine leukemia virus in the TLL mouse causes site-specific differences in lymphoma/leukemia frequency and tumor immunophenotype
- 2006
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 26:4B, s. 2873-2878
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Tidskriftsartikel (refereegranskat)abstract
- Background: Moloney murine leukemia virus (Mo-MLV) has proven valuable for studies of the pathogenesis of malignant lymphoma. Inoculation of newborn mice induces T cell lymphoma with 100% incidence. The TLL (T cell lymphoma/leukemia)-strain was previously established and was shown to spontaneously develop T cell lymphoma at high frequency. Materials and Methods: Differential screening of cDNA libraries was performed to discover an involvement of Mo-MLV and genomic sequencing was used to identify the chromosomal position of Mo-MLV proviral integration sites. Immunophenotypes of the tumors were established by flow cytometry. Disease frequency curves were created according to the Kaplan-Meier method. Results: Two independent Mo-MLV germ line integrations were characterized on chromosomes 2 and 14, giving rise to two substrains of mice denoted TLL-2 and TLL-14. The chromosomal position of the integrated provirus affected the frequency of disease, as well as the immunophenotype of the tumors. Conclusion: The data suggest that factors influencing the transcriptional activity of the chromosomal regions, leading to differences in proviral expression, could underlie the observed difference in tumor frequency.
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| 5. |
- Nygren, Ulrika Svea, et al.
(författare)
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Team-based visits within Swedish child healthcare services : a national cross-sectional study
- 2024
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Ingår i: Journal of Interprofessional Care. - : Taylor & Francis. - 1356-1820 .- 1469-9567.
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Tidskriftsartikel (refereegranskat)abstract
- Complex healthcare needs can be met through effective interprofessional collaboration. Since 2014, Swedish Child Healthcare Services (CHS) include universal team-based visits with a nurse and a physician who perform such visits at the age of 4 weeks, 6 months, 12 months, and 2.5 to 3 years, as well as targeted team-based visits to address additional needs. The aim of this study was to describe the prevalence of team-based visits in the Swedish CHS and possible associations between team-based visits and contextual factors that may affect its implementation. A national cross-sectional survey was conducted using a web-based questionnaire distributed to all reachable nurses, physicians, and psychologists (n =3,552) engaged in the CHS. Data were analyzed using descriptive statistics and binary and multivariate logistic regressions. The response rate was 32%. Team-based visits were reported by 82% of the respondents. For nurses and physicians, the most frequent indication was specific ages, while for psychologists it was to provide parental support. Respondents working at Family Centers were more likely to perform team-based visits in general, at 2.5 to 3 years and in case of additional needs, compared to respondents working at Child Health Centers (CHC) and other workplaces. In conclusion, team-based visits are well implemented, but the pattern differs depending on the contextual factors. Targeted team-based visits and team-based visits at the age of 2.5 to 3 years are most unequally implemented.
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| 6. |
- Söderlund, Carina, et al.
(författare)
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Visuell Management, smart kommunikation och design : Tavlor för visuell styrning, planering, uppföljning och i förbättringsarbetet
- 2020
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Boken du håller i är ett delresultat från projekt Vis’man som handlar om designforskning inom visuell och spatial kommunikation och management från användarens perspektiv. I projektet har vi studerat visualiseringens roll och funktion inom visuell management och de tavlor som används vid visuell ledning, planering och uppföljning och i förbättringsarbetet. Det kan vara målstyrningstavlor, Lean-tavlor, teamtavlor, styrtavlor med flera. Ett mål har varit att undersöka och utveckla tavlorna och deras omgivning tillsammans med projektdeltagarna. Dessutom har metoder för användarmedverkan tagits fram, för att olika aktörer ska tillsammans kunna undersöka, utveckla och utvärdera informationsdesign inom visuell management. Projektet har finansierats av KK-stiftelsen genom programmet HÖG. Vi som deltagit är forskare i forskargruppen Informationsdesign vid Mälardalens högskola och industriforskare från Rise i Mölndal. Projektet har utförts tillsammans med svensk tillverkningsindustri, Volvo Construction Equipment i Eskilstuna, Union Electrics Åkers, Falks Metall AB och Gårö Plåtprodukter AB. Studier har även skett tillsammans med Vård och omsorgsförvaltningen vid Eskilstuna kommun. Den här boken presenterar teorier och metoder som relaterar till visuell management, samt erfarenheter från praktiken. Boken vänder sig till dig som har viss yrkeserfarenhet av visuell management och till studenter som studerar informationsdesign, servicedesign, gränssnittsdesign, produkt- och processutveckling, ledning och styrning eller liknande områden.
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| 7. |
- Adolfsson, Karin, et al.
(författare)
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Referral of patients with cancer to palliative care: Attitudes, practices and work-related experiences among Swedish physicians
- 2022
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Ingår i: European Journal of Cancer Care. - : Hindawi Limited. - 0961-5423 .- 1365-2354. ; 31:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective This study aimed to explore the attitudes, practices and work-related experiences among Swedish physicians regarding the referral process, integration and transition between oncology care and palliative care (PC). Methods A cross-sectional online survey was performed with a study-specific questionnaire in 2016-2017 in south-eastern Sweden. Physicians working with cancer patients within surgical specialties, medical specialties and paediatric oncology participated. Results The vast majority of the 130 participating physicians (99.2%) stated that PC was beneficial for the patient and were positive about early integration of PC (65.5%). Still, only 27.6% of the participants introduced PC at an early stage of non-curable disease. However, paediatric oncologists had a very early introduction of PC in comparison with medical specialties (p = 0.004). Almost 90% of the study population said they wanted to know that the patient had been taken care of by another care facility. Conclusions Despite the physicians' positive attitude towards early integration and referral to PC, they often acted late in the disease trajectory. This late approach can reduce the patient's opportunity of improving quality of life during severe circumstances. There is a need for in-depth knowledge of the physicians' challenges in order to bridge the gap between intentions and actions.
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| 8. |
- Alijagic, Andi, 1992-, et al.
(författare)
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Immunotoxic, genotoxic, and endocrine disrupting impacts of polyamide microplastic particles and chemicals
- 2024
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 183
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Tidskriftsartikel (refereegranskat)abstract
- Due to their exceptional properties and cost effectiveness, polyamides or nylons have emerged as widely used materials, revolutionizing diverse industries, including industrial 3D printing or additive manufacturing (AM). Powder-based AM technologies employ tonnes of polyamide microplastics to produce complex components every year. However, the lack of comprehensive toxicity assessment of particulate polyamides and polyamide-associated chemicals, especially in the light of the global microplastics crisis, calls for urgent action. This study investigated the physicochemical properties of polyamide-12 microplastics used in AM, and assessed a number of toxicity endpoints focusing on inflammation, immunometabolism, genotoxicity, aryl hydrocarbon receptor (AhR) activation, endocrine disruption, and cell morphology. Specifically, microplastics examination by means of field emission scanning electron microscopy revealed that work flow reuse of material created a fraction of smaller particles with an average size of 1-5 µm, a size range readily available for uptake by human cells. Moreover, chemical analysis by means of gas chromatography high-resolution mass spectrometry detected several polyamide-associated chemicals including starting material, plasticizer, thermal stabilizer/antioxidant, and migrating slip additive. Even if polyamide particles and chemicals did not induce an acute inflammatory response, repeated and prolonged exposure of human primary macrophages disclosed a steady increase in the levels of proinflammatory chemokine Interleukin-8 (IL-8/CXCL-8). Moreover, targeted metabolomics disclosed that polyamide particles modulated the kynurenine pathway and some of its key metabolites. The p53-responsive luciferase reporter gene assay showed that particles per se were able to activate p53, being indicative of a genotoxic stress. Polyamide-associated chemicals triggered moderate activation of AhR and elicited anti-androgenic activity. Finally, a high-throughput and non-targeted morphological profiling by Cell Painting assay outlined major sites of bioactivity of polyamide-associated chemicals and indicated putative mechanisms of toxicity in the cells. These findings reveal that the increasing use of polyamide microplastics may pose a potential health risk for the exposed individuals, and it merits more attention.
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| 9. |
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| 10. |
- Aranda Muñoz, Alvaro, et al.
(författare)
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Co-Designing with AI in Sight
- 2022
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Ingår i: Proceedings of the Design Society. - : Cambridge University Press (CUP). - 2732-527X. ; 2, s. 101-110, s. 101-110
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Tidskriftsartikel (refereegranskat)abstract
- Artificial Intelligence offers a wide variety of capabilities that can potentially address people's needs and desires in their specific contexts. This pilot study presents a collaborative method using a deck of AI cards tested with 58 production, AI, and information science students, and experts from an accessible media agency. The results suggest that, with the support of the method and AI cards, participants can ideate and reach conceptual AI solutions. Such conceptualisations can contribute to a more inclusive integration of AI solutions in society.
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