| 1. |
- Hellgren, Margareta, 1955, et al.
(författare)
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The burden of poor glycaemic control in people with newly diagnosed type 2 diabetes in Sweden: A health economic modelling analysis based on nationwide data
- 2021
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Ingår i: Diabetes, obesity and metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 23:7, s. 1604-1613
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Tidskriftsartikel (refereegranskat)abstract
- Aim To evaluate the economic and clinical burden associated with poor glycaemic control in Sweden, in people with type 2 diabetes (T2D) initiating first-line glucose-lowering therapy. Materials and Methods Population data were obtained from Swedish national registers. Immediate glycaemic control was compared with delays in achieving control of 1 and 3 years, with outcomes projected over 3, 10 and 50 years in the validated IQVIA CORE Diabetes Model. Glycaemic control was defined as glycated haemoglobin (HbA1c) targets of 52, 48 and 42 mmol/mol, as recommended in Swedish guidelines, according to age and disease duration. Costs (expressed in 2019 Swedish krona [SEK]) were accounted from a Swedish societal perspective. Results Immediate glycaemic control was associated with population-level cost savings of up to SEK 279 million and SEK 673 million versus delays of 1 and 3 years, respectively, as well as small population-level life expectancy benefits of up to 1305 and 2590 life years gained. Reduced levels of burden were a result of lower incidence and delayed time to onset of diabetes-related complications. Conclusions Even in people with T2D initiating first-line glucose-lowering therapy, the economic burden of poor glycaemic control in Sweden is substantial, but could be reduced by early and effective treatment to achieve glycaemic targets.
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| 2. |
- Lönnberg, Tapio, et al.
(författare)
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Single-cell RNA-seq and computational analysis using temporal mixture modelling resolves Th1/Tfh fate bifurcation in malaria
- 2017
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Ingår i: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 2:9
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Tidskriftsartikel (refereegranskat)abstract
- Differentiation of naïve CD4(+) T cells into functionally distinct T helper subsets is crucial for the orchestration of immune responses. Due to extensive heterogeneity and multiple overlapping transcriptional programs in differentiating T cell populations, this process has remained a challenge for systematic dissection in vivo. By using single-cell transcriptomics and computational analysis using a temporal mixtures of Gaussian processes model, termed GPfates, we reconstructed the developmental trajectories of Th1 and Tfh cells during blood-stage Plasmodium infection in mice. By tracking clonality using endogenous TCR sequences, we first demonstrated that Th1/Tfh bifurcation had occurred at both population and single-clone levels. Next, we identified genes whose expression was associated with Th1 or Tfh fates, and demonstrated a T-cell intrinsic role for Galectin-1 in supporting a Th1 differentiation. We also revealed the close molecular relationship between Th1 and IL-10-producing Tr1 cells in this infection. Th1 and Tfh fates emerged from a highly proliferative precursor that upregulated aerobic glycolysis and accelerated cell cycling as cytokine expression began. Dynamic gene expression of chemokine receptors around bifurcation predicted roles for cell-cell in driving Th1/Tfh fates. In particular, we found that precursor Th cells were coached towards a Th1 but not a Tfh fate by inflammatory monocytes. Thus, by integrating genomic and computational approaches, our study has provided two unique resources, a database www.PlasmoTH.org, which facilitates discovery of novel factors controlling Th1/Tfh fate commitment, and more generally, GPfates, a modelling framework for characterizing cell differentiation towards multiple fates.
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| 3. |
- Proserpio, Valentina, et al.
(författare)
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Single-cell analysis of CD4+ T-cell differentiation reveals three major cell states and progressive acceleration of proliferation
- 2016
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Ingår i: Genome Biology. - : BioMed Central. - 1465-6906 .- 1474-760X. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Differentiation of lymphocytes is frequently accompanied by cell cycle changes, interplay that is of central importance for immunity but is still incompletely understood. Here, we interrogate and quantitatively model how proliferation is linked to differentiation in CD4+ T cells.RESULTS: We perform ex vivo single-cell RNA-sequencing of CD4+ T cells during a mouse model of infection that elicits a type 2 immune response and infer that the differentiated, cytokine-producing cells cycle faster than early activated precursor cells. To dissect this phenomenon quantitatively, we determine expression profiles across consecutive generations of differentiated and undifferentiated cells during Th2 polarization in vitro. We predict three discrete cell states, which we verify by single-cell quantitative PCR. Based on these three states, we extract rates of death, division and differentiation with a branching state Markov model to describe the cell population dynamics. From this multi-scale modelling, we infer a significant acceleration in proliferation from the intermediate activated cell state to the mature cytokine-secreting effector state. We confirm this acceleration both by live imaging of single Th2 cells and in an ex vivo Th1 malaria model by single-cell RNA-sequencing.CONCLUSION: The link between cytokine secretion and proliferation rate holds both in Th1 and Th2 cells in vivo and in vitro, indicating that this is likely a general phenomenon in adaptive immunity.
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| 4. |
- Willquist, Karin, et al.
(författare)
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Design of a novel biohythane process with high H2 and CH4 production rates
- 2012
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Ingår i: International Journal of Hydrogen Energy. - : Elsevier BV. - 1879-3487 .- 0360-3199. ; 37:23, s. 17749-17762
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Tidskriftsartikel (refereegranskat)abstract
- A biohythane process based on wheat straw including: i) pretreatment, ii) H2 production using Caldicellulosiruptor saccharolyticus, iii) CH4 production using an undefined consortium, and iv) gas upgrading using an amine solution, was assessed through process modelling including cost and energy analysis. According to simulations, a biohythane gas with the composition 46–57% H2, 43–54% CH4 and 0.4% CO2, could be produced at high production rates (2.8–6.1 L/L/d), with 93% chemical oxygen demand (COD) reduction, and a net energy yield of 7.4–7.7 kJ/g dry straw. The model was calibrated and verified using experimental data from dark fermentation (DF) of wheat straw hydrolysate, and anaerobic digestion of DF effluent. In addition, the effect of gas recirculation was investigated by both wet experiments and simulation. Sparging improved H2 productivities and yields, but negatively affected the net energy gain and cost of the overall process.
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