| 1. |
- Jadersten, M., et al.
(författare)
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Targeting SAMHD1 with hydroxyurea in first-line cytarabine-based therapy of newly diagnosed acute myeloid leukaemia: Results from the HEAT-AML trial
- 2022
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 292:6, s. 925-940
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Tidskriftsartikel (refereegranskat)abstract
- Background Treatment of newly diagnosed acute myeloid leukaemia (AML) is based on combination chemotherapy with cytarabine (ara-C) and anthracyclines. Five-year overall survival is below 30%, which has partly been attributed to cytarabine resistance. Preclinical data suggest that the addition of hydroxyurea potentiates cytarabine efficacy by increasing ara-C triphosphate (ara-CTP) levels through targeted inhibition of SAMHD1. Objectives In this phase 1 trial, we evaluated the feasibility, safety and efficacy of the addition of hydroxyurea to standard chemotherapy with cytarabine/daunorubicin in newly diagnosed AML patients. Methods Nine patients were enrolled and received at least two courses of ara-C (1 g/m(2)/2 h b.i.d. d1-5, i.e., a total of 10 g/m(2) per course), hydroxyurea (1-2 g d1-5) and daunorubicin (60 mg/m(2) d1-3). The primary endpoint was safety; secondary endpoints were complete remission rate and measurable residual disease (MRD). Additionally, pharmacokinetic studies of ara-CTP and ex vivo drug sensitivity assays were performed. Results The most common grade 3-4 toxicity was febrile neutropenia (100%). No unexpected toxicities were observed. Pharmacokinetic analyses showed a significant increase in median ara-CTP levels (1.5-fold; p = 0.04) in patients receiving doses of 1 g hydroxyurea. Ex vivo, diagnostic leukaemic bone marrow blasts from study patients were significantly sensitised to ara-C by a median factor of 2.1 (p = 0.0047). All nine patients (100%) achieved complete remission, and all eight (100%) with validated MRD measurements (flow cytometry or real-time quantitative polymerase chain reaction [RT-qPCR]) had an MRD level <0.1% after two cycles of chemotherapy. Treatment was well-tolerated, and median time to neutrophil recovery >1.0 x 10(9)/L and to platelet recovery >50 x 10(9)/L after the start of cycle 1 was 19 days and 22 days, respectively. Six of nine patients underwent allogeneic haematopoietic stem-cell transplantation (allo-HSCT). With a median follow-up of 18.0 (range 14.9-20.5) months, one patient with adverse risk not fit for HSCT experienced a relapse after 11.9 months but is now in second complete remission. Conclusion Targeted inhibition of SAMHD1 by the addition of hydroxyurea to conventional AML therapy is safe and appears efficacious within the limitations of the small phase 1 patient cohort. These results need to be corroborated in a larger study.
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| 2. |
- Kuschmierz, Paul, et al.
(författare)
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European first-year university students accept evolution but lack substantial knowledge about it : A standardized European cross-country assessment
- 2021
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Ingår i: Evolution. - : BioMed Central (BMC). - 1936-6426 .- 1936-6434. ; 14:1, s. 1-22
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Tidskriftsartikel (refereegranskat)abstract
- Background: Investigations of evolution knowledge and acceptance and their relation are central to evolution education research. Ambiguous results in this field of study demonstrate a variety of measuring issues, for instance differently theorized constructs, or a lack of standardized methods, especially for cross-country comparisons. In particular, meaningful comparisons across European countries, with their varying cultural backgrounds and education systems, are rare, often include only few countries, and lack standardization. To address these deficits, we conducted a standardized European survey, on 9200 first-year university students in 26 European countries utilizing a validated, comprehensive questionnaire, the “Evolution Education Questionnaire”, to assess evolution acceptance and knowledge, as well as influencing factors on evolution acceptance. Results: We found that, despite European countries’ different cultural backgrounds and education systems, European first-year university students generally accept evolution. At the same time, they lack substantial knowledge about it, even if they are enrolled in a biology-related study program. Additionally, we developed a multilevel-model that determines religious faith as the main influencing factor in accepting evolution. According to our model, knowledge about evolution and interest in biological topics also increase acceptance of evolution, but to a much lesser extent than religious faith. The effect of age and sex, as well as the country’s affiliation, students’ denomination, and whether or not a student is enrolled in a biology-related university program, is negligible. Conclusions: Our findings indicate that, despite all their differences, most of the European education systems for upper secondary education lead to acceptance of evolution at least in university students. It appears that, at least in this sample, the differences in knowledge between countries reflect neither the extent to which school curricula cover evolutionary biology nor the percentage of biology-related students in the country samples. Future studies should investigate the role of different European school curricula, identify particularly problematic or underrepresented evolutionary concepts in biology education, and analyze the role of religious faith when teaching evolution.
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| 3. |
- Ahlström, A., et al.
(författare)
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No major differences in perinatal and maternal outcomes between uninterrupted embryo culture in time-lapse system and conventional embryo culture
- 2023
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Ingår i: Human Reproduction. - : Oxford University Press. - 0268-1161 .- 1460-2350. ; 38:12, s. 2400-2411
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Is embryo culture in a closed time-lapse system associated with any differences in perinatal and maternal outcomes in comparison to conventional culture and spontaneous conception?SUMMARY ANSWER: There were no significant differences between time-lapse and conventional embryo culture in preterm birth (PTB, <37 weeks), low birth weight (LBW, >2500 g) and hypertensive disorders of pregnancy for singleton deliveries, the primary outcomes of this study.WHAT IS KNOWN ALREADY: Evidence from prospective trials evaluating the safety of time-lapse incubation for clinical use show similar embryo development rates, implantation rates, and ongoing pregnancy and live birth rates when compared to conventional incubation. Few studies have investigated if uninterrupted culture can alter risks of adverse perinatal outcomes presently associated with IVF when compared to conventional culture and spontaneous conceptions.STUDY DESIGN, SIZE, DURATION: This study is a Swedish population-based retrospective registry study, including 7379 singleton deliveries after fresh embryo transfer between 2013 and 2018 from selected IVF clinics. Perinatal outcomes of singletons born from time-lapse-cultured embryos were compared to singletons from embryos cultured in conventional incubators and 71 300 singletons from spontaneous conceptions. Main perinatal outcomes included PTB and LBW. Main maternal outcomes included hypertensive disorders of pregnancy (pregnancy hypertension and preeclampsia).PARTICIPANTS/MATERIALS, SETTING, METHODS: From nine IVF clinics, 2683 singletons born after fresh embryo transfer in a time-lapse system were compared to 4696 singletons born after culture in a conventional incubator and 71 300 singletons born after spontaneous conception matched for year of birth, parity, and maternal age. Patient and treatment characteristics from IVF deliveries were cross-linked with the Swedish Medical Birth Register, Register of Birth Defects, National Patient Register and Statistics Sweden. Children born after sperm and oocyte donation cycles and after Preimplantation Genetic testing cycles were excluded. Odds ratio (OR) and adjusted OR were calculated, adjusting for relevant confounders.MAIN RESULTS AND THE ROLE OF CHANCE: In the adjusted analyses, no significant differences were found for risk of PTB (adjusted OR 1.11, 95% CI 0.87-1.41) and LBW (adjusted OR 0.86, 95% CI 0.66-1.14) or hypertensive disorders of pregnancy; preeclampsia and hypertension (adjusted OR 0.99, 95% CI 0.67-1.45 and adjusted OR 0.98, 95% CI 0.62-1.53, respectively) between time-lapse and conventional incubation systems. A significantly increased risk of PTB (adjusted OR 1.31, 95% CI 1.08-1.60) and LBW (adjusted OR 1.36, 95% CI 1.08-1.72) was found for singletons born after time-lapse incubation compared to singletons born after spontaneous conceptions. In addition, a lower risk for pregnancy hypertension (adjusted OR 0.72 95% CI 0.53-0.99) but no significant difference for preeclampsia (adjusted OR 0.87, 95% CI 0.68-1.12) was found compared to spontaneous conceptions. Subgroup analyses showed that some risks were related to the day of embryo transfer, with more adverse outcomes after blastocyst transfer in comparison to cleavage stage transfer.LIMITATIONS, REASONS FOR CAUTION: This study is retrospective in design and different clinical strategies may have been used to select specific patient groups for time-lapse versus conventional incubation. The number of patients is limited and larger datasets are required to obtain more precise estimates and adjust for possible effect of additional embryo culture variables.WIDER IMPLICATIONS OF THE FINDINGS: Embryo culture in time-lapse systems is not associated with major differences in perinatal and maternal outcomes, compared to conventional embryo culture, suggesting that this technology is an acceptable alternative for embryo incubation.
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| 4. |
- Bohlin, I, et al.
(författare)
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Mapping potential location for bilberry picking with remote sensing, local field data andphone application
- 2023
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the study was to create a practical method for identifying potential locations for bilberry picking with help of remote sensing, local field data and phone application to support the development of the local berry value chain. Local field data w as collected 2021 and 2022 and consisted 503 and 525 plots from a study area of circa 25x45km in Västerbotten, Sweden. The potential for bilberry production was evaluated by measuring the shrub cover and amount of raw berries. Wall to wall remote sensing d ata included a Sentinel 2 image from same summer, airborne laser scanning data from 2020 and other map products. We created classification models for bilberry shrub and yield using both logistic regression (2 classes) and ordinal regression (3 classes) mod els using 2021 data, and validated and calibrated models with 2022 data. Predictor variables consisted of spectral metrics from satellite data; structural metrics from laser data; existing raster maps of tree species, stand attributes, site index, soil moi sture and land use classes. The 2 class models performed better than three class models, delivering the AUC 0.73, overall accuracy 0.83 and kappa value 0.51 for best bilberry shrub model and 0.75, 0.77 and 0.50 respectively for best bilberry yield model. T he best models included both laser based structural metrics describing e.g canopy closure and spectral metrics, but also e.g. volume of pine, soil moisture and site index were found significant predictor variables. Calibration of the models improved annual predictions and the validation of the 2021 raster maps with 2022 data produced similar AUC, OA, and kappa values for bilberry yield (0.73, 0.74 and 0.46), but lower for bilberry shrub (0.61, 0.68 and 0.24). A dedicated phone application was developed duri ng the project, which was used both for collecting the field data and for presenting the potential locations of berry yields. Local berry maps can help berry pickers easier to find the berries in forest landscape and therefore support local berry value cha in. This study is part of the FAIRCHAIN project, which has received funding from the European Union’s funding programme H2020 research and innovation programme under grand agreement 101000723.
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| 5. |
- Gout, Thomas L., et al.
(författare)
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Temperature dependent lithium isotope fractionation during glass dissolution
- 2021
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Ingår i: Geochimica et Cosmochimica Acta. - : Elsevier. - 0016-7037 .- 1872-9533. ; 313, s. 133-154
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the mechanisms by which borosilicate glasses corrode in contact with aqueous solutions remains a challenge to the safety case for the geological disposal of vitrified high-level nuclear waste. Here, lithium isotope fingerprinting techniques were applied to the leachates of a simulant Magnox waste glass to probe the mechanisms of aqueous corrosion at both short and long timescales (6 hours to 464 days). Experiments took place at 40 and 90 degrees C to assess the consistency of the dissolution mechanisms across a range of commonly employed temperatures and the legitimacy of applying higher temperature experimental datasets to understand glass corrosion within a disposal facility at lower temperatures. Two competing release mechanisms were observed for lithium (diffusion and hydrolysis), and the relative proportions of these mechanisms changed through time. Leachates initially had lower delta(7) Li values than the pristine glass (-2.7 parts per thousand at 40 degrees C and 1.1 parts per thousand at 90 degrees C relative to the pristine glass) at both temperatures due to lithium leaching incongruently through diffusive processes. The greater offset between solution and solid at lower temperatures indicates a larger rate of diffusion (incongruent dissolution) relative to the rate of hydrolysis (congruent dissolution) at lower temperatures. The fraction of lithium released through diffusion relative to the fraction of lithium released through hydrolysis then increased at both temperatures with time up to 126 days, increasing from 0.47 and 0.22 at 6 hours to 0.66 and 0.41 at 126 days at 40 and 90 degrees C respectively. Subsequently, the fractions of lithium released through diffusion sharply decreased to 0.36 at 40 degrees C and 0.22 at 90 degrees C after 464 days, consistent with network hydrolysis coupled with secondary phase precipitation later controlling the long-term release of Li at both temperatures. Throughout the duration of the experiments (464 days) the delta(7) Li values in solution increased to 9.0 parts per thousand at 40 degrees C and 10.0 parts per thousand at 90 degrees C due to the formation of talc and montmorillonite phases at 40 degrees C and additional smectite phases at 90 degrees C. Further, no evidence for the formation of a diffusive barrier to the transport of Li within the alteration layers became apparent during the later stages of dissolution at either temperature. However, the fraction of lithium leached through diffusion was still significant throughout all stages of dissolution. Lithium isotope ratios in solution were correlated with the transition from a system which was increasingly dominated by lithium diffusion as the dissolution rate slowed to one which was controlled by hydrolysis coupled with secondary phase precipitation at long durations. Alongside elemental ratios in solution, these results were consistent with the same set of mechanisms governing dissolution across the temperature range studied.
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| 6. |
- Gustafsson, Jenny, 1990-
(författare)
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Drömmen om en gränslös fred : Världsmedborgarrörelsens reaktopi, 1949-1968
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In postwar France, a new movement – Citoyens du Monde – emerged with the aim to unite people across the world around the political target of achieving world peace through dissolving the national borders and establishing a worldwide society. In 1949, Världsmedborgarrörelsen (the World Citizen Movement) was established in Sweden as the 21st branch of the movement and represented the new ism mondialism.The aim of the study is to understand and explain the ideas that propelled Världsmedborgarrörelsen, and how these ideas emerged, evolved and faded away in relation to the prevailing political circumstances. Theoretically, the dissertation draws on formation of -isms and approaches to political temporality. The study is supported by Hannah Arendt’s posited gap in time between memory and expectation as a crucial precondition for political actors as they temporally orient themselves to establish new policies. The study argues that the temporal orientation of world citizens was based on a gap in time filled by the idea that World War II had demonstrated the failure of traditional politics. Furthermore, the would-be citizens of the world forged their political expectations through a ”reactopia”; they presented a utopian political dream to ward off an imagined dystopia of nuclear war. Having experienced World War II and now living under the very real threat of nuclear weapons, Världsmedborgarrörelsen proclaimed that nation states, with their intergovernmental strife and division of people, were paving the way to new wars. By the time Världsmedborgarrörelsen dissolved in the 1960s, it appeared to be a prisoner of its own reactopian temporal orientation. Memories of World War II had faded and the threat of nuclear war diminished. As the new political boundary was drawn between Global North and Global South, the movement found it difficult to mobilise its forces.
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| 7. |
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| 8. |
- Mayer, Ludovic, et al.
(författare)
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Widespread Pesticide Distribution in the European Atmosphere Questions their Degradability in Air
- 2024
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Ingår i: Environmental Science and Technology. - 0013-936X. ; 58:7, s. 3342-3352
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Tidskriftsartikel (refereegranskat)abstract
- Risk assessment of pesticide impacts on remote ecosystems makes use of model-estimated degradation in air. Recent studies suggest these degradation rates to be overestimated, questioning current pesticide regulation. Here, we investigated the concentrations of 76 pesticides in Europe at 29 rural, coastal, mountain, and polar sites during the agricultural application season. Overall, 58 pesticides were observed in the European atmosphere. Low spatial variation of 7 pesticides suggests continental-scale atmospheric dispersal. Based on concentrations in free tropospheric air and at Arctic sites, 22 pesticides were identified to be prone to long-range atmospheric transport, which included 15 substances approved for agricultural use in Europe and 7 banned ones. Comparison between concentrations at remote sites and those found at pesticide source areas suggests long atmospheric lifetimes of atrazine, cyprodinil, spiroxamine, tebuconazole, terbuthylazine, and thiacloprid. In general, our findings suggest that atmospheric transport and persistence of pesticides have been underestimated and that their risk assessment needs to be improved.
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