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| 2. |
- Malmgren, Linnea, et al.
(författare)
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The complexity of kidney disease and diagnosing it - Cystatin C, selective glomerular hypofiltration syndromes and proteome regulation.
- 2023
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 293:3, s. 293-308
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Tidskriftsartikel (refereegranskat)abstract
- Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous GFR-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterised by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules < 1kDa dominating the glomerular filtrate e.g., water, urea, creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterised by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines.
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| 3. |
- Andersson, Camilla, et al.
(författare)
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Achievements and experiences from science–policy interaction in the field of air pollution : Synthesising 20 years of research and outreach,thinking about future needs
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- For 20 years, the Swedish Environmental Protection Agency together with the MISTRA research foundation have funded five air pollution research programmes with focus on producing knowledge that supports policy and emission control in national and international arenas. The research has been multidisciplinary and has included research on emissions, atmospheric transport and transformation processes, human health effects, ecosystem effects, and emission control strategies. Research has also been conducted on the interaction between air pollution and climate change.Over these years, the link between the research programmes and the development of emission control strategies and policies in Sweden, the EU, and the UNECE Air Convention has been of high importance. This report presents how the research programmes have created societal benefits through support for the development of air pollution policies and emission control measures. The report also identifies future research needs to ensure continued progress towards even better air quality for future generations.
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| 4. |
- Artaxo, Paulo, et al.
(författare)
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Tropical and Boreal Forest – Atmosphere Interactions : A Review
- 2022
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Ingår i: Tellus. Series B, Chemical and physical meteorology. - : Stockholm University Press. - 0280-6509 .- 1600-0889. ; 74:1, s. 24-163
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Forskningsöversikt (refereegranskat)abstract
- This review presents how the boreal and the tropical forests affect the atmosphere, its chemical composition, its function, and further how that affects the climate and, in return, the ecosystems through feedback processes. Observations from key tower sites standing out due to their long-term comprehensive observations: The Amazon Tall Tower Observatory in Central Amazonia, the Zotino Tall Tower Observatory in Siberia, and the Station to Measure Ecosystem-Atmosphere Relations at Hyytiäla in Finland. The review is complemented by short-term observations from networks and large experiments.The review discusses atmospheric chemistry observations, aerosol formation and processing, physiochemical aerosol, and cloud condensation nuclei properties and finds surprising similarities and important differences in the two ecosystems. The aerosol concentrations and chemistry are similar, particularly concerning the main chemical components, both dominated by an organic fraction, while the boreal ecosystem has generally higher concentrations of inorganics, due to higher influence of long-range transported air pollution. The emissions of biogenic volatile organic compounds are dominated by isoprene and monoterpene in the tropical and boreal regions, respectively, being the main precursors of the organic aerosol fraction.Observations and modeling studies show that climate change and deforestation affect the ecosystems such that the carbon and hydrological cycles in Amazonia are changing to carbon neutrality and affect precipitation downwind. In Africa, the tropical forests are so far maintaining their carbon sink.It is urgent to better understand the interaction between these major ecosystems, the atmosphere, and climate, which calls for more observation sites, providing long-term data on water, carbon, and other biogeochemical cycles. This is essential in finding a sustainable balance between forest preservation and reforestation versus a potential increase in food production and biofuels, which are critical in maintaining ecosystem services and global climate stability. Reducing global warming and deforestation is vital for tropical forests.
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| 5. |
- Balador, Ali, et al.
(författare)
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AORTA: Advanced Offloading for Real-time Applications
- 2023
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Konferensbidrag (refereegranskat)abstract
- We are currently witnessing the second wave of cloud services that go beyond web storefronts and IT systems, aiming for digitalization of industrial systems. Automation and time-sensitive systems are now taking their first steps toward the cloud. The AORTA project aims to facilitate this transition by providing key technology components needed for real-time services running in the cloud. The ambition is to support a future robotics ecosystem that enables a new level of flexible productivity in industrial production. AORTA will develop technologies that allow offloading of real-time services/functions to the edge and cloud. We will build upon recent advances in 5G, cloud, and networking technologies. The AORTA framework will support a fluid compute model where functionality will be dynamically deployed locally, in the edge, or in the cloud and support integration and real-time performance irrespective of where it executes. Results of the project will be demonstrated in a real-world robotics manufacturing and construction scenarios operating via a 5G network with real-time edge and large-scale cloud service. The AORTA technologies will provide opportunities for automation enterprises and system integrators by adding real-time capabilities needed to evolve beyond the currently closed ecosystem. They will also add value to telecom providers and operators that may host these new automation services in addition to their current portfolio.
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| 6. |
- Björklund, Erik, et al.
(författare)
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Comparison of Midterm Outcomes Associated With Aspirin and Ticagrelor vs Aspirin Monotherapy After Coronary Artery Bypass Grafting for Acute Coronary Syndrome.
- 2021
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Ingår i: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 4:8
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Tidskriftsartikel (refereegranskat)abstract
- Guidelines recommend dual antiplatelet therapy after coronary artery bypass grafting (CABG) for patients with acute coronary syndrome (ACS). However, the evidence for these recommendations is weak.To compare midterm outcomes after CABG in patients with ACS treated postoperatively with acetylsalicylic acid (ASA) and ticagrelor or with ASA monotherapy.This cohort study used merged data from several national registries of Swedish patients who were diagnosed with ACS and subsequently underwent CABG. All included patients underwent isolated CABG in Sweden between 2012 and 2017 with an ACS diagnosis less than 6 weeks before the procedure, survived 14 days after discharge from hospital, and were treated postoperatively with ASA plus ticagrelor or ASA monotherapy. A multivariable Cox regression model was used for the main analysis, and propensity score-matched models were performed as sensitivity analysis. Data were analyzed between May and September 2020.Postoperative antiplatelet treatment, defined as filled prescriptions, with either ASA and ticagrelor or ASA only.Major adverse cardiovascular events (MACE), defined as all-cause mortality, myocardial infarction, and stroke, and major bleeding, at 12 months and at the end of follow-up.A total of 6558 patients (5281 [80.5%] men; mean [SD] age at surgery, 67.6 [9.3] years) were included; 1813 (27.6%) were treated with ASA plus ticagrelor and 4745 (72.4%) were treated with ASA monotherapy. Crude MACE rate was 3.0 per 100 person years (95% CI, 2.5-3.6 per 100 person years) in the ASA plus ticagrelor group and 3.8 per 100 person years (95% CI, 3.5-4.1 per 100 person years) in the ASA group. After adjustment, there was no significant difference in MACE risk between ASA plus ticagrelor vs ASA only, neither during the first 12 months (adjusted hazard ratio [aHR], 0.84; 95% CI, 0.58-1.21; P=.34) or during total follow-up (aHR, 0.89; 95% CI, 0.71-1.11; P=.29). The use of ASA plus ticagrelor was associated with a significantly increased risk for major bleeding during the first 12 months (aHR, 1.90; 95% CI, 1.16-3.13; P=.011). Sensitivity analyses confirmed the results.In patients with ACS who survived 2 weeks after CABG, no significant difference in the risk of death or ischemic events could be demonstrated between ASA plus ticagrelor and patients treated with ASA only, while the risk for major bleeding was higher in patients treated with ASA plus ticagrelor. Sufficiently powered prospective randomized trials comparing different antiplatelet therapy strategies after CABG are warranted.
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| 7. |
- Björklund, Erik, et al.
(författare)
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Postdischarge major bleeding, myocardial infarction, and mortality risk after coronary artery bypass grafting
- 2023
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Ingår i: HEART. - 1355-6037 .- 1468-201X.
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the incidence and mortality risk associated with postdischarge major bleeding after coronary artery bypass grafting (CABG), and relate this to the incidence of, and mortality risk from, postdischarge myocardial infarction.Methods All patients undergoing first-time isolated CABG in Sweden in 2006-2017 and surviving 14 days after hospital discharge were included in a cohort study. Individual patient data from the SWEDEHEART Registry and five other mandatory nationwide registries were merged. Piecewise Cox proportional hazards models were used to investigate associations between major bleeding, defined as hospitalisation for bleeding, with subsequent mortality risk. Similar Cox proportional hazards models were used to investigate the association between postdischarge myocardial infarction and mortality risk.Results Among 36 633 patients, 2429 (6.6%) had a major bleeding event and 2231 (6.1%) had a myocardial infarction. Median follow-up was 6.0 (range 0-11) years. Major bleeding was associated with higher mortality risk <30 days (adjusted HR (aHR)=20.2 (95% CI 17.3 to 23.5)), 30-365 days (aHR=3.8 (95% CI 3.4 to 4.3)) and >365 days (aHR=1.8 (95% CI 1.7 to 2.0)) after the event. Myocardial infarction was associated with higher mortality risk <30 days (aHR=20.0 (95% CI 16.7 to 23.8)), 30-365 days (aHR=4.1 (95% CI 3.6 to 4.8)) and >365 days (aHR=1.8 (95% CI 1.7 to 2.0)) after the event.Conclusions The increase in mortality risk associated with a postdischarge major bleeding after CABG is substantial and is similar to the mortality risk associated with a postdischarge myocardial infarction.
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| 8. |
- Degerstedt, Oliver, et al.
(författare)
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Drug diffusion in biomimetic hydrogels : importance for drug transport and delivery in non-vascular tumor tissue
- 2022
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier. - 0928-0987 .- 1879-0720. ; 172
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Tidskriftsartikel (refereegranskat)abstract
- Hydrogels of varying complexity are routinely used as scaffolds and 3D structures for in vitro tumor models to increase physiological relevance within pre-clinical cancer research. Relatively simple hydrogels such as agarose are well characterised, meanwhile biomimetic gels containing collagen and fibrin(ogen) have been studied to a much lesser extent. In this study, hydrogels mimicking the biophysical characteristics of liver cancer progression were investigated in terms of their UV-properties and influence on diffusion coefficients of different substances. UV-imaging technology was used to both visualize and quantify the diffusion process in a simple and rapid way. In general, agarose gel diffusion agreed well with predictions using the Stokes-Einstein equation meanwhile the biomimetic gels reduced diffusion coefficients by up to 70%. For doxorubicin, spatio-temporal tissue concentration modelling was used to translate in vitro diffusion to the more clinical context of tumor penetration in a solid liver tumor supplied by arterial blood.
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| 9. |
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| 10. |
- Degerstedt, Oliver
(författare)
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Translational Tumor Drug Delivery : Doxorubicin formulation performance, intracellular uptake and molecular diffusion
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Globally, hepatocellular carcinoma (HCC) is the most common form of liver cancer and a leading cause of cancer death. One important risk factor is liver cirrhosis and the disease progression is characterized by deposition of extracellular matrix proteins that form a fibrous network, which increases liver stiffness and may limit the effectiveness of different treatment strategies. The overall aim of this thesis was to investigate the anticancer drug doxorubicin (DOX) and its clinically relevant drug delivery systems from an in vitro perspective. The focus was on developing and using qualitative and quantitative methods to better understand formulation performance, intracellular uptake and molecular diffusion. The experimental in vitro findings were then translated to clinical scenarios using physiologically based pharmacokinetic (PBPK) modelling.The performance of clinically employed emulsion formulations containing DOX and the tumor accumulating oil Lipiodol® were evaluated in terms of their stability (Paper I). The most stable emulsion (> 72 h) was achieved when using an aqueous phase containing the contrast agent iohexol and with an aqueous to lipid phase ratio of 1:4 to assure formation of a water-in-oil emulsion. This was followed by a cell-based study (Paper II) where nanoformulated DOX was compared to DOX in solution in terms of tumor cell toxicity, intracellular DOX uptake and intracellular formation of the main active metabolite doxorubicinol (DOXol). DOX in solution was more potent in all investigated cell lines, where the most sensitive cells (HepG2) displayed IC50 values that were approximately 100 times lower than the most resistant cell line (SNU449). This was explained by the rapid intracellular uptake in HepG2 cells which was also confirmed with a complimentary miniaturized chip technique in Paper IV. In papers III and IV the focus was on molecular diffusion across biomimetic hydrogels mimicking tissue properties of cirrhotic liver and early stage HCC. The diffusion of DOX was significantly reduced in biomimetic gels as compared with more commonly used agarose gels, however the presence of human liver tumor cells did not significantly influence diffusion. Simulations using a developed PBPK and spatio-temporal tissue concentration model suggested that a liver tumor resembling SNU449 cells would not reach therapeutic exposure levels in a clinical scenario while the diffusion of DOX required further reduction by the tumor extracellular matrix in order to generate tumor concentration-time curves consistent with in vivo observations.This thesis contributes to an increased understanding of using DOX and its drug delivery systems as a treatment option for HCC. The approach of translating in vitro experimental data to clinical scenarios using modelling will grow in relevance as methods become more complex and data more bio-relevant.
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| 11. |
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| 12. |
- Schmitz, Alexander, et al.
(författare)
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Longitudinal minimal residual disease assessment in multiple myeloma patients in complete remission : results from the NMSG flow-MRD substudy within the EMN02/HO95 MM trial
- 2022
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Ingår i: BMC Cancer. - : BMC. - 1471-2407. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple myeloma remains an incurable disease with multiple relapses due to residual myeloma cells in the bone marrow of patients after therapy. Presence of small number of cancer cells in the body after cancer treatment, called minimal residual disease, has been shown to be prognostic for progression-free and overall survival. However, for multiple myeloma, it is unclear whether patients attaining minimal residual disease negativity may be candidates for treatment discontinuation. We investigated, if longitudinal flow cytometry-based monitoring of minimal residual disease (flow-MRD) may predict disease progression earlier and with higher sensitivity compared to biochemical assessments. Methods: Patients from the Nordic countries with newly diagnosed multiple myeloma enrolled in the European-Myeloma-Network-02/Hovon-95 (EMN02/HO95) trial and undergoing bone marrow aspiration confirmation of complete response, were eligible for this Nordic Myeloma Study Group (NMSG) substudy. Longitdudinal flow-MRD assessment of bone marrow samples was performed to identify and enumerate residual malignant plasma cells until observed clinical progression. Results: Minimal residual disease dynamics were compared to biochemically assessed changes in serum free light chain and M-component. Among 20 patients, reaching complete response or stringent complete response during the observation period, and with >= 3 sequential flow-MRD assessments analysed over time, increasing levels of minimal residual disease in the bone marrow were observed in six cases, preceding biochemically assessed disease and clinical progression by 5.5 months and 12.6 months (mean values), respectively. Mean malignant plasma cells doubling time for the six patients was 1.8 months (95% CI, 1.4-2.3 months). Minimal malignant plasma cells detection limit was 4 x 10-5. Conclusions: Flow-MRD is a sensitive method for longitudinal monitoring of minimal residual disease dynamics in multiple myeloma patients in complete response. Increasing minimal residual disease levels precedes biochemically assessed changes and is an early indicator of subsequent clinical progression.
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