| 1. |
- Adams, Yvonne, et al.
(författare)
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3D blood-brain barrier-organoids as a model for Lyme neuroborreliosis highlighting genospecies dependent organotropism
- 2023
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Ingår i: ISCIENCE. - : CELL PRESS. - 2589-0042. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Lyme neuroborreliosis (LNB), a tick-borne infection caused by spirochetes within the Borrelia burgdorferi sensu lato (s.L.) complex, is among the most prevalent bacterial central nervous system (CNS) infections in Europe and the US. Here we have screened a panel of low- passage B. burgdorferi s.l. isolates using a novel, human-derived 3D blood-brain barrier (BBB)-organoid model. We show that human-derived BBB-organoids support the entry of Borrelia spirochetes, leading to swelling of the organoids and a loss of their structural integrity. The use of the BBB-organoid model highlights the organotropism between B. burgdorferi s.l. genospecies and their ability to cross the BBB contributing to CNS infection.
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| 2. |
- Anthon, Carl Thomas, et al.
(författare)
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Platelet transfusions in adult ICU patients with thrombocytopenia : A sub-study of the PLOT-ICU inception cohort study
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Platelet transfusions are frequently used in the intensive care unit (ICU), but current practices including used product types, volumes, doses and effects are unknown.STUDY DESIGN AND METHODS: Sub-study of the inception cohort study 'Thrombocytopenia and Platelet Transfusions in the ICU (PLOT-ICU)', including acutely admitted, adult ICU patients with thrombocytopenia (platelet count <150 × 10 9/L). The primary outcome was the number of patients receiving platelet transfusion in ICU by product type. Secondary outcomes included platelet transfusion details, platelet increments, bleeding, other transfusions and mortality. RESULTS: Amongst 504 patients with thrombocytopenia from 43 hospitals in 10 countries in Europe and the United States, 20.8% received 565 platelet transfusions; 61.0% received pooled products, 21.9% received apheresis products and 17.1% received both with a median of 2 (interquartile range 1-4) days from admission to first transfusion. The median volume per transfusion was 253 mL (180-308 mL) and pooled products accounted for 59.1% of transfusions, however, this varied across countries. Most centres (73.8%) used fixed dosing (medians ranging from 2.0 to 3.5 × 10 11 platelets/transfusion) whilst some (mainly in France) used weight-based dosing (ranging from 0.5 to 0.7 × 10 11 platelets per 10 kg body weight). The median platelet count increment for a single prophylactic platelet transfusion was 2 (-1 to 8) × 10 9/L. Outcomes of patients with thrombocytopenia who did and did not receive platelet transfusions varied. CONCLUSIONS: Among acutely admitted, adult ICU patients with thrombocytopenia, 20.8% received platelet transfusions in ICU of whom most received pooled products, but considerable variation was observed in product type, volumes and doses across countries. Prophylactic platelet transfusions were associated with limited increases in platelet counts.
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| 3. |
- Christensen, Sarah Friis, et al.
(författare)
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Healthcare resource utilization in patients with myeloproliferative neoplasms: A Danish nationwide matched cohort study
- 2022
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Ingår i: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609.
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Tidskriftsartikel (refereegranskat)abstract
- Few studies have assessed healthcare resource utilization (HRU) in patients with Philadelphia-negative myeloproliferative neoplasms (MPN) using a matched cohort design. Further, no detailed assessment of HRU in the years preceding an MPN diagnosis exists. We conducted a registry-based nationwide Danish cohort study, including patients with essential thrombocythemia, polycythemia vera, myelofibrosis, and unclassifiable MPN diagnosed between January 2010 and December 2016. HRU data were summarized annually from 2 years before MPN diagnosis until emigration, death, or end of study (December 2017). We included 3342 MPN patients and 32 737 comparisons without an MPN diagnosis, matched on sex, age, region of residence, and level of education. During the study period, the difference in HRU (rate ratio) between patients and matched comparisons ranged from 1.0 to 1.5 for general practitioner contacts, 0.9 to 2.2 for hospitalizations, 0.9 to 3.8 for inpatient days, 1.0 to 4.0 for outpatient visits, 1.3 to 2.1 for emergency department visits, and 1.0 to 4.1 for treatments/examinations. In conclusion, MPN patients had overall higher HRU than the matched comparisons throughout the follow-up period (maximum 8 years). Further, MPN patients had substantially increased HRU in both the primary and secondary healthcare sector in the 2 years preceding the diagnosis.
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| 4. |
- Christensen, Sarah Friis, et al.
(författare)
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Labor Market Attachment in Patients with Myeloproliferative Neoplasms: A Nationwide Matched Cohort Study
- 2021
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 138:Suppl 1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Myeloproliferative neoplasms (MPNs) are characterized by a substantial symptom burden, risk of debilitating complications (e.g., thrombosis), and increased comorbidity. Recently, three comprehensive questionnaire studies (Mesa 2016, Harrison 2017, Jingbo 2018) have reported a high impact of MPNs on patients' ability to work. However, no registry-based studies have assessed labor market attachment (LMA) of MPN patients and matched nonMPN comparisons.AIM: To assess the pre- and post-diagnostic LMA of MPN patients and matched nonMPN comparisons.METHODS: We conducted a descriptive, registry-based nationwide cohort study, using data from the Danish National Chronic Myeloid Neoplasia Registry including all Danish MPN patients diagnosed between January 2010 and December 2016. Population-based cohorts of nonMPN comparisons were constructed by 1:10 matching on age, sex, level of education, and region of residence. Data on LMA were retrieved from the Danish Register for Evaluation of Marginalization, which holds information on all public transfer payments in Denmark. Data were linked using the unique civil registration number, which identifies all Danish citizens. The LMA endpoints were defined for each individual as working (not receiving any type of transfer payment), unemployed, receiving transfer payment for either sick leave, disability pension, age pension, or other health-related benefits (e.g., wage-subsidized employment). We assessed LMA weekly for each individual from two years before diagnosis until death, emigration, or two years after the diagnosis. For each cohort, we presented LMA as proportions with 95% confidence intervals (CIs), as well as the proportion of individuals who died during follow-up.RESULTS: The study included 3,342 MPN patients (1,140 essential thrombocythemia [ET]; 1,109 polycythemia vera [PV]; 533 myelofibrosis [MF]; and 560 unspecified MPN [MPN-U]) and 32,737 nonMPN comparisons (11,181 nonET; 10,873 nonPV; 5,217 nonPMF; and 5,466 nonMPN-U). The median age at time of diagnosis was: ET 67 years (interquartile range [IQR], 55-76); PV, 69 years (IQR, 61-77); PMF, 73 years (IQR, 66-79); and MPN-U, 72 years (IQR, 63-80).At time of MPN diagnosis, the majority of MPN patients and nonMPN comparisons received age pension (range: ET, 52.1% [95% CI, 49.2-55.0] to nonMF, 70.3% [95% CI, 69.1-71.6]). The proportions working were: ET, 35.1% (95% CI, 32.3-37.9) vs. nonET, 37.3% (95% CI, 36.5-38.2); PV, 22.6% (95% CI, 20.2-25.1) vs. nonPV, 30.8% (95% CI, 29.9-31.7); MF, 23.8% (95% CI, 20.2-27.4) vs. nonMF, 23.6% (95% CI, 22.5-24.8); and MPN-U, 22.1% (95% CI,18.7- 25.6) vs. nonMPN-U, 27.8% (95% CI, 26.6-29.0). Across MPN subtypes, a larger proportion of patients than comparisons were on sick leave: ET, 3.5% (95% CI, 2.4-4.6) vs. nonET, 1.3% (95% CI, 1.1-1.5); PV, 5.5% (95% CI, 4.2-6.8) vs. nonPV, 0.9% (95% CI, 0.7-1.1); MF (not applicable due to small numbers) vs. nonMF, 0.6% (95% CI, 0.4-0.8); and MPN-U, 3.0% (95% CI, 1.6- 4.5) vs. nonMPN-U, 1.0% (95% CI, 0.7-1.3). Regarding disability pension, the proportions ranged from 4.1% (95% CI, 2.4-5.8) to 5.0% (95% CI, 3.7-6.3) among patients and from 3.1% (95% CI, 2.6-3.6) to 4.7% (95% CI, 4.3-5.1) among comparisons. For both MPN patients and nonMPN comparisons, few were unemployed (≤3.3%) or received other health-related benefits (≤1.6%).Two years preceding diagnosis, the proportion of PV and MPN-U patients working was slightly lower than the matched comparisons: PV, 31.0% (95% CI, 28.4-33.8) vs. nonPV, 34.3% (95% CI, 33.5-35.2) and MPN-U, 28.2% (95% CI, 24.6-32.1) vs. nonMPN-U, 32.0% (95% CI, 30.7-33.2), while this difference was not observed between ET and MF patients and their respective comparisons.From two years before to two years after diagnosis, we observed slightly larger reductions in the proportion working among MPN patients than among comparisons. Among MPN patients, the proportion on sick leave including other health-related benefits, increased during the study period, while it remained unchanged among comparisons. The proportion of patients and comparisons on disability pension remained stable.CONCLUSION: Overall, our findings showed that Danish patients with ET, PV, MF, and MPN-U had slightly impaired LMA already two years before diagnosis and up to two years after diagnosis. Thus, fewer patients were working and more patients transferred to sick leave compared with matched individuals without MPN.
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| 5. |
- Christensen, Sarah, et al.
(författare)
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Healthcare resource utilization in patients with myeloproliferative neoplasms: a nationwide matched cohort study
- 2021
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Ingår i: HemaSphere. - : Ovid Technologies (Wolters Kluwer Health). - 2572-9241. ; 5:S2, s. 529-530
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Tidskriftsartikel (refereegranskat)abstract
- Background: Myeloproliferative neoplasms (MPNs) are associated with severe complications and a substantial symptom burden – frequently emerging several years before diagnosis. Due to the chronic nature ofthe diseases, MPN patients have a lifelong need for treatment and care. However, only few studies have assessed MPN healthcare resource utilization (HRU) compared with matched cohorts, and no detailed assessments of HRU in the years preceding MPN diagnosis exist.Aims: To assess the pre- and post-diagnostic HRU of MPN patients compared with matched cohorts of nonMPN comparisons.Methods: We conducted this descriptive, register-based nationwide cohort study, utilizing data from the Danish National Chronic Myeloid Neoplasia Registry on all MPN patients diagnosed between January 2010 and December 2016, and data on HRU from the Danish National Patient Registry and the Danish National Health Service Registry. Populationbased cohorts of nonMPN comparisons were constructed by 1:10 matchingon age, sex, level of education, and region of residence. Data were linkedusing the unique civil registration number, which identifies all Danish citizens. HRU was summarized over each year for all cohorts from twoyears before date of MPN diagnosis and until emigration, death, or endof study (31 December 2017). HRU was calculated as annual number ofhealthcare contacts (inpatient days, outpatient consultations, treatmentsand examinations, and general practitioner [GP] visits) divided by person-years at risk and compared using rate ratios with 95% CI.Results: The study population included 3,342 MPN patients (1,140 essential thrombocythemia [ET]; 1,109 polycythemia vera [PV]; 533 primary myelofibrosis [PMF]; and 560 unspecified MPN [MPN-U]) and 32,737 nonMPN comparisons (11,181 nonET; 10,873 nonPV; 5,217 nonPMF; and 5,466 nonMPN-U). The median age was 67 (ET), 69 (PV), 73 (PMF), and 72 years (MPN-U), and the mean follow-up was 3.8 (ET), 3.8(PV), 3.1 (PMF), and 3.3 years (MPN-U). A total of 750 (22.4%) MPNpatients and 4,627 (14.1%) nonMPN comparisons died during follow-up.In nearly all years of follow-up, MPN patients had a higher HRU thannonMPN comparisons (Figure, rate ratio>1). Rate ratios for outpatientconsultations were largest at the time of diagnosis: ET, 2.7 (95%CI, 2.6-2.9); PV, 3.4 (95%CI, 3.2-3.6); PMF, 4.0 (95%CI, 3.7-4.4); and MPN-U,3.7 (95%CI, 3.4-4.0). For most MPN subtypes, rate ratios also peaked attime of diagnosis for treatment and examinations. In contrast, the largest rate ratio for PV was in the last year of follow-up: 3.5 (95%CI, 2.8-4.3). Across MPN subtypes, rate ratios for GP visits varied from 1.0 to1.5 during follow-up without any considerable fluctuations. Interestingly, increased rate ratios for inpatients days were evident 2 years before diagnosis: ET, 1.8 (95%CI, 1.7-1.9); PV, 1.3, (95%CI, 1.2-1.3); PMF, 1.4(95%CI, 1.2-1.5); and MPN-U, 1.7 (95%CI, 1.6-1.9). During follow-up,notable increases in rate ratios were observed, e.g., PMF 3.0 (95%CI 2.4-3.6) and PV 3.8 (95%CI 3.0-4.8) in year 5 and 7, respectively.Summary/Conclusion: Overall, compared with matched nonMPN comparisons, MPN patients had a higher HRU throughout the study period. This was consistent across MPN subtypes and HRU measures. Within the limitations of small numbers toward end of follow-up and lack ofmatching on comorbidity, our findings confirmed a consistent HRU burden after MPN diagnosis. Equally important, our study revealed substantial increases in HRU two years before MPN diagnosis, warrantingfurther exploration of the pre-diagnostic period, including the potentialbenefits of early detection.
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| 6. |
- Christiansen, Alexandra Golabek, et al.
(författare)
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Occupational exposure to epoxy components and risk of dermatitis : A registry-based follow-up study of the wind turbine industry
- 2024
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Ingår i: Contact Dermatitis. - 0105-1873. ; 90:1, s. 32-40
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allergic contact allergy and dermatitis are frequently reported among epoxy-exposed workers. Objectives: To determine the risk of dermatitis associated with epoxy exposure. Methods: We followed 825 epoxy-exposed and 1091 non-exposed blue-collar workers, and 493 white-collar workers of a Danish wind turbine blade factory during 2017–2022 with linked data from national health registers on diagnoses, patch testing, or fillings of prescriptions for topical corticosteroids. Incidence rate ratios of dermatitis or a first-time topical corticosteroid prescription were estimated with Poisson regression using non-exposed blue-collar workers as reference. We similarly estimated incidence rate ratios for the duration of epoxy exposure and current epoxy exposure. Results: Epoxy-exposed blue-collar workers showed a dermatitis incidence rate of 2.1 per 100 000 person days, a two-fold increased risk of dermatitis and a 20% increased risk of filling a prescription for topical corticosteroids. Incidence rate ratios were higher during early exposure and declined with further exposure for both outcomes. White-collar workers had generally lower risks. Conclusion: We observed an increased risk of dermatitis following epoxy exposure confirming previous case reports and cross-sectional studies emphasizing the need for intensified focus on preventive efforts for this group of workers.
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| 7. |
- Christiansen, Alexandra G., et al.
(författare)
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Prevalence of skin sensitization and dermatitis among epoxy-exposed workers in the wind turbine industry
- 2022
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 187:6, s. 988-996
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Tidskriftsartikel (refereegranskat)abstract
- Background: A high prevalence of skin sensitization and dermatitis has been reported among workers exposed to epoxy components. Objectives: To estimate the risk of skin sensitization and dermatitis among workers exposed to epoxy components during production of wind turbine blades while using comprehensive safety measures. Methods: A cross-sectional study of 180 highly epoxy-exposed production workers and 41 nonexposed office workers was conducted at two wind turbine blade factories in Denmark. Participants underwent a skin examination, were tested with a tailored patch test panel including epoxy-containing products used at the factories, and answered a questionnaire. Results: Sixteen production workers (8·9%) were sensitized to an epoxy component compared with none of the office workers. Skin sensitization was more frequent within the first year of exposed employment. Strong selection bias by atopic status was indicated. Among nonatopic workers, the prevalence of dermatitis was higher among production workers (16·4%) than among office workers [6·5%, odds ratio (OR) 2·3, 95% confidence interval (CI) 0·6–9·1] and higher among the sensitized workers (43·8%) than the nonsensitized workers (14·6%, OR 4·5, 95% CI 1·6–12·7). Resins based on diglycidyl ether of bisphenol A and F were the most frequent sensitizers. One of the four workers sensitized to epoxy components used at the factories did not react to the epoxy resin of the TRUE test® panel. Conclusions: Despite comprehensive skin protection, sensitization and dermatitis are prevalent among highly epoxy-exposed workers in the wind turbine industry in Denmark. Our findings document the need for intensified preventive efforts and emphasize the importance of tailored patch testing. What is already known about this topic? Epoxy components are well-known sensitizers of the skin. A high prevalence of skin sensitization and dermatitis has been reported among workers exposed to epoxy components. Comprehensive protective equipment is recommended when working with epoxy components. What does this study add? Despite comprehensive skin protection, skin sensitization and dermatitis are prevalent among epoxy-exposed workers. We found that 40% of workers sensitized to epoxy products had dermatitis. Only 75% of the sensitized workers were detected by the epoxy resin of the TRUE test®, which emphasizes the importance of tailored testing.
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| 8. |
- Clausen, Geo, et al.
(författare)
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Children's health and its association with indoor environments in Danish homes and daycare centres - methods
- 2012
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Ingår i: Indoor Air. - : Hindawi Limited. - 0905-6947 .- 1600-0668. ; 22:6, s. 467-475
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Tidskriftsartikel (refereegranskat)abstract
- The principle objective of the Danish research program 'Indoor Environment and Children's Health' (IECH) was to explore associations between various exposures that children experience in their indoor environments (specifically their homes and daycare centers) and their well-being and health. The targeted health endpoints were allergy, asthma, and certain respiratory symptoms. The study was designed with two stages. In the first stage, a questionnaire survey was distributed to more than 17000 families with children between the ages of 1 and 5. The questionnaire focused on the children's health and the environments within the homes they inhabited and daycare facilities they attended. More than 11000 questionnaires were returned. In the second stage, a subsample of 500 children was selected for more detailed studies, including an extensive set of measurements in their homes and daycare centers and a clinical examination; all clinical examinations were carried out by the same physician. In this study, the methods used for data collection within the IECH research program are presented and discussed. Furthermore, initial findings are presented regarding descriptors of the study population and selected characteristics of the children's dwellings and daycare centers. Practical Implications: This study outlines methods that might be followed by future investigators conducting large-scale field studies of potential connections between various indoor environmental factors and selected health endpoints. Of particular note are (i) the two-stage design - a broad questionnaire-based survey followed by a more intensive set of measurements among a subset of participants who have been selected based on their responses to the questionnaire; (ii) the case-base approach utilized in the stage 2 in contrast to the more commonly used case-control approach; (iii) the inclusion of the children's daycare environment when conducting intensive sampling to more fully capture the children's total indoor exposure; and (iv) all clinical examinations conducted by the same physician. We recognize that future investigators are unlikely to fully duplicate the methods outlined in this study, but we hope that it provides a useful starting point in terms of factors that might be considered when designing such a study.
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| 9. |
- Clausen, Thomas Mandel, et al.
(författare)
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A simple method for detecting oncofetal chondroitin sulfate glycosaminoglycans in bladder cancer urine
- 2020
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Ingår i: Cell Death Discovery. - : Springer Science and Business Media LLC. - 2058-7716. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Proteoglycans in bladder tumors are modified with a distinct oncofetal chondroitin sulfate (ofCS) glycosaminoglycan that is normally restricted to placental trophoblast cells. This ofCS-modification can be detected in bladder tumors by the malarial VAR2CSA protein, which in malaria pathogenesis mediates adherence of parasite-infected erythrocytes within the placenta. In bladder cancer, proteoglycans are constantly shed into the urine, and therefore have the potential to be used for detection of disease. In this study we investigated whether recombinant VAR2CSA (rVAR2) protein could be used to detect ofCS-modified proteoglycans (ofCSPGs) in the urine of bladder cancer patients as an indication of disease presence. We show that ofCSPGs in bladder cancer urine can be immobilized on cationic nitrocellulose membranes and subsequently probed for ofCS content by rVAR2 protein in a custom-made dot-blot assay. Patients with high-grade bladder tumors displayed a marked increase in urinary ofCSPGs as compared to healthy individuals. Urine ofCSPGs decreased significantly after complete tumor resection compared to matched urine collected preoperatively from patients with bladder cancer. Moreover, ofCSPGs in urine correlated with tumor size of bladder cancer patients. These findings demonstrate that rVAR2 can be utilized in a simple biochemical assay to detect cancer-specific ofCS-modifications in the urine of bladder cancer patients, which may be further developed as a noninvasive approach to detect and monitor the disease.
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| 10. |
- Haake, Magnus, et al.
(författare)
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Scaffolding mentalizing via a play-&-learn game for preschoolers
- 2015
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Ingår i: Computers & Education. - : Elsevier BV. - 0360-1315 .- 1873-782X. ; 90, s. 13-23
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Tidskriftsartikel (refereegranskat)abstract
- Educational software in which the student takes the role of teacher and instructs a digital tutee a so-called teachable agent has repeatedly proven to have positive effects for school children's learning. In a study with 39 preschoolers aged 3:9 to 6:3, we explored the conditions under which children this young would benefit as well from this kind of educational software. We specifically investigated to what extent children of this age group would be able to reason about and reflect upon the actions of their digital tutee, and to what extent they would enjoy an educational game centered around instructing and helping a digital tutee. Results revealed that preschoolers were quite capable of reasoning and reflecting upon their digital tutee. This was rather surprising, since the results of a standardized false-belief test did not indicate this level of mentalizing capabilities in the group as a whole. The results also indicated that the preschoolers, like older children, were interested and engaged in this kind of game that involves instructing a digital tutee. (C) 2015 Elsevier Ltd. All rights reserved.
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