| 1. |
- Philippot, Gaetan, et al.
(författare)
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A Cannabinoid Receptor Type 1 (CB1R) Agonist Enhances the Developmental Neurotoxicity of Acetaminophen (Paracetamol)
- 2018
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Ingår i: Toxicological Sciences. - : OXFORD UNIV PRESS. - 1096-6080 .- 1096-0929. ; 166:1, s. 203-212
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Tidskriftsartikel (refereegranskat)abstract
- Acetaminophen (AAP; also known as paracetamol) is the most used and only recommended analgesic and antipyretic among pregnant women and young children. However, recent findings in both humans and rodents suggest a link between developmental exposure to AAP and adverse neurobehavioral effects later in life. We hypothesized that the cannabinoid receptor type 1 (CB1R) may be involved in the developmental neurotoxicity of AAP, owing to its interaction with the endocannabinoid system. Here we test if CB1R agonist WIN 55 212-2 (WIN) and AAP can interact when exposure occurs during a neurodevelopmental stage known for increased growth rate and for its vulnerability to AAP exposure. We exposed male NMRI mice on postnatal day 10 to different combinations of AAP and WIN. Adult mice, neonatally co-exposed to AAP and WIN, displayed a significant lack of habituation in the spontaneous behavior test, when compared with controls and single agent exposed mice. These adult adverse effects may at least in part be explained by a reduction of transcript levels of hippocampal synaptophysin (Syp) and tropomyosin receptor kinase B (Trkb), and cerebral cortical fatty acid amide hydroxylase (Faah), 24h after exposure. These findings are consistent with our hypothesis that AAP and WIN can interact when exposure occurs during early postnatal brain development in mice. Assuming our results are relevant for humans, they raise concerns on AAP safety because it is the only recommended analgesic and antipyretic during pregnancy and early life.
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| 2. |
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| 3. |
- Brusini, Irene, et al.
(författare)
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Changes in brain architecture are consistent with altered fear processing in domestic rabbits
- 2018
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:28, s. 7380-7385
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Tidskriftsartikel (refereegranskat)abstract
- The most characteristic feature of domestic animals is their change in behavior associated with selection for tameness. Here we show, using high-resolution brain magnetic resonance imaging in wild and domestic rabbits, that domestication reduced amygdala volume and enlarged medial prefrontal cortex volume, supporting that areas driving fear have lost volume while areas modulating negative affect have gained volume during domestication. In contrast to the localized gray matter alterations, white matter anisotropy was reduced in the corona radiata, corpus callosum, and the subcortical white matter. This suggests a compromised white matter structural integrity in projection and association fibers affecting both afferent and efferent neural flow, consistent with reduced neural processing. We propose that compared with their wild ancestors, domestic rabbits are less fearful and have an attenuated flight response because of these changes in brain architecture.
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| 4. |
- Buratovic, Sonja, 1986-, et al.
(författare)
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Effects on adult cognitive function after neonatal exposure to clinically relevant doses of ionising radiation and ketamine in mice
- 2018
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Ingår i: British Journal of Anaesthesia. - : ELSEVIER SCI LTD. - 0007-0912 .- 1471-6771. ; 120:3, s. 546-554
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Tidskriftsartikel (refereegranskat)abstract
- Background: Radiological methods for screening, diagnostics and therapy are frequently used in healthcare. In infants and children, anaesthesia/sedation is often used in these situations to relieve the patients' perception of stress or pain. Both ionising radiation (IR) and ketamine have been shown to induce developmental neurotoxic effects and this study aimed to identify the combined effects of these in a murine model. Methods: Male mice were exposed to a single dose of ketamine (7.5 mg kg(-1) body weight) s.c. on postnatal day 10. One hour after ketamine exposure, mice were whole body irradiated with 50-200 mGy gamma radiation (Cs-137). Behavioural observations were performed at 2, 4 and 5 months of age. At 6 months of age, cerebral cortex and hippocampus tissue were analysed for neuroprotein levels. Results: Animals co-exposed to IR and ketamine displayed significant (P <= 0.01) lack of habituation in the spontaneous behaviour test, when compared with controls and single agent exposed mice. In the Morris Water Maze test, co-exposed animals showed significant (P <= 0.05) impaired learning and memory capacity in both the spatial acquisition task and the relearning test compared with controls and single agent exposed mice. Furthermore, in co-exposed mice a significantly (P <= 0.05) elevated level of tau protein in cerebral cortex was observed. Single agent exposure did not cause any significant effects on the investigated endpoints. Conclusion: Co-exposure to IR and ketamine can aggravate developmental neurotoxic effects at doses where the single agent exposure does not impact on the measured variables. These findings show that estimation of risk after paediatric low-dose IR exposure, based upon radiation dose alone, may underestimate the consequences for this vulnerable population.
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| 5. |
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| 6. |
- Buratovic, Sonja, 1986-
(författare)
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Low-Dose Ionizing Radiation Induces Neurotoxicity in the Neonate : Acute or fractionated doses and interaction with xenobiotics in mice
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis examines the developmental neurotoxic effects of exposure to low-dose ionizing radiation (IR), alone or together with xenobiotics, during a critical period of neonatal brain development in mice.During mammalian brain development there is a period called the brain growth spurt (BGS), which involves extensive growth and maturation of the brain. It is known that neonatal exposure during the BGS to xenobiotics can have a negative impact on neonatal brain development, resulting in impaired cognitive function in the adult mouse. In humans, the BGS starts during the third trimester of pregnancy and continues for approximately 2 years in the child. The present thesis has identified a defined critical period, during the BGS, when IR can induce developmental neurotoxicity in mice. The observed neurotoxicity was not dependent on sex or strain and manifested as altered neurobehaviour in the adult mouse. Furthermore, fractionated dose exposures appear to be as potent as a higher acute dose. The cholinergic system can be a target system for developmental neurotoxicity of IR, since alterations in adult mouse cholinergic system susceptibility were observed. Co-exposure to IR and nicotine exacerbated the behavioural disturbances and cholinergic system dysfunction. Furthermore, co-exposure with the environmental agent paraquat has indicated that the dopaminergic system can be a potential target. In this thesis, clinically relevant doses of IR and a sedative/anesthetic agent (ketamine) were shown to interact and exacerbate defects in adult mouse neurobehaviour, learning and memory, following neonatal exposure, at doses where the single agents did not have any impact on the measured variables. This indicates a shift in the dose-response curve for IR, towards lower doses, if exposure occurs during the neonatal brain development. In addition, co-exposed mice, showing cognitive defects, expressed elevated levels of tau protein in the cerebral cortex. Furthermore, exacerbation of neurochemical deviations were observed following co-exposure compared to irradiation alone.Further investigations of neurotoxic effects following fractionated or acute low-dose IR, modelling the clinical situation during repeated CT scans or levels of radiation deposited in non-target tissue during radiotherapy, and possible interaction effects with xenobiotics, is of great importance in the field of radioprotection.
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| 7. |
- Bäckström, Daniel, 1985, et al.
(författare)
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On the use of alternative fuels in rotary kiln burners - An experimental and modelling study of the effect on the radiative heat transfer conditions
- 2015
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Ingår i: Fuel processing technology. - : Elsevier. - 0378-3820 .- 1873-7188. ; 138, s. 210-220
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Tidskriftsartikel (refereegranskat)abstract
- Abstract In this work, the radiative heat transfer conditions in a 400 kWfuel test furnace were studied. The test furnace is a scaled pilot of a rotary kiln furnace used in iron ore pellet production. In particular, the study focuses on the choice of fuel and the subsequent effect on temperature and radiative conditions in the flame. Several co-firing flames of coal and biomass were investigated and also other fuels such as heavy fuel oil and natural gas. The test furnace was used in the experiments, and radiative intensity was measured with a narrow angle radiometer. Detailed radiation modelling was performed using spectral models for gas and particle properties. The results show that all co-firing flames give a shorter radiating flame length. Based on the radiation modelling, it was also shown that the particle radiation dominates the heat transfer from the flames. Due to the high pre-heating temperature of the combustion air (1100°C), the flame temperatures were generally very high. The flame temperature in the natural gas flame was likely around 2000°C while the coal flame temperatures were estimated to 1500-1600°C. The two coals tested, having almost identical fuel specifications, resulted in a substantial difference in the radiation intensity emitted by the flame. This emphasizes the need of direct radiation measurements to evaluate fuel changes in industrial processes that are highly dependent on the heat transfer conditions.
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| 8. |
- Fredholm, Hanna, et al.
(författare)
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Breast cancer in young women and prognosis : How important are proliferation markers?
- 2017
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 84, s. 278-289
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Tidskriftsartikel (refereegranskat)abstract
- Aim:Compared to middle-aged women, young women with breast cancer have a higher risk of systemic disease. We studied expression of proliferation markers in relation to age and subtype and their association with long-term prognosis.Methods:Distant disease-free survival (DDFS) was studied in 504 women aged <40 years and 383 women aged >= 40 years from a population-based cohort. Information on patient characteristics, treatment and follow-up was collected from medical records. Tissue microarrays were produced for analysis of oestrogen receptor, progesterone receptor (PR), Her2, Ki-67 and cyclins.Results: Young women with luminal tumours had significantly higher expression of Ki-67 and cyclins. Proliferation markers were prognostic only within this subtype. Ki-67 was a prognostic indicator only in young women with luminal PR+ tumours. The optimal cut-off for Ki-67 varied by age. High expression of cyclin E1 conferred a better DDFS in women aged <40 years with luminal PR- tumours (hazard ratio [HR] 0.47 [0.24-0.92]). Age < 40 years was an independent risk factor of DDFS exclusively in women with luminal B PR+ tumours (HR 2.35 [1.22-4.50]). Young women with luminal B PR- tumours expressing low cyclin E1 had a six-fold risk of distant disease compared with luminal A ( HR 6.21 [2.17-17.6]).Conclusions:The higher expression of proliferation markers in young women does not have a strong impact on prognosis. Ki-67 is only prognostic in the subgroup of young women with luminal PR tumours. The only cyclin adding prognostic value beyond subtype is cyclin E1. Age is an independent prognostic factor only in women with luminal B PR+ tumours.
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| 9. |
- Fredholm, Hanna, et al.
(författare)
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Long-term outcome in young women with breast cancer : a population-based study
- 2016
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 160:1, s. 131-143
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Tidskriftsartikel (refereegranskat)abstract
- Whether young age at diagnosis of breast cancer is an independent risk factor for death remains controversial, and the question whether young age should be considered in treatment decisions is still to be answered. From a population-based cohort of 22,017 women with breast cancer, all women < 35 years (n = 471) were compared to a random sample of 700 women aged 35-69 years from the same cohort. Information on patient and tumor characteristics, treatment, and follow-up was collected from the medical records. Tissue microarrays were produced for analysis of classical biomarkers. Breast cancer-specific survival (BCSS), distant disease-free survival (DDFS), and locoregional recurrence-free survival (LRFS) by age were compared using women 50-69 years as reference. At 10 years follow-up, women < 35 years and 35-39 years had a worse BCSS [age < 35 years 69 % (HR 2.75, 95 % CI 1.93-3.94), age 35-39 years 76 % (HR 2.33, 95 % CI 1.54-3.52), age 40-49 years 84 % (HR 1.53, 95 % CI 0.97-2.39), and age 50-69 years 89 % (reference)]. The worse BCSS was statistically significant in stages I-IIa and Luminal B tumors. At multivariate analysis age < 35 years and 35-39 years confined a risk in LRFS (HR 2.13, 95 % CI 1.21-3.76 and HR 1.97, 95 % CI 1.06-3.68) but not in DDFS and BCSS. In the subgroup of women < 40 years with luminal tumors stage I-IIa, low age remained an independent risk factor also in DDFS (HR 1.87, 95 % CI 1.03-3.44). Young women have a high risk of systemic disease even when diagnosed in an early stage. The excess risk of relapse is most pronounced in Luminal B tumors, where low age is an independent prognostic factor of DDFS and LRFS.
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| 10. |
- Fredriksson, Anna, 1979-, et al.
(författare)
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Hur taktisk planering kan underlätta resursplanering i byggbranschen – Processer och IT-verktyg
- 2017
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Syftet med denna artikel är att visa på hur resurser inom byggföretag kan planeras på taktisk nivå med hjälp av optimeringsverktyg. Den rådande högkonjunkturen i Sverige med högre efterfrågan från beställare än vad byggentreprenörerna kan levererar måste entreprenörerna aktivt välja vilka projekt man ska gå in med anbud på. Beslutet måste vara välgrundat på information gällande efterfrågade projekt, tillgängliga resurser och potentiell vinstmarginal på projekten. Det är här taktisk planering kommer in genom att balansera potentiella projekt med den kapacitet byggföretaget har för att kunna gå in med anbud på de projekt som genererar högst vinstmarginal. Genom att studera två byggföretag (NCC och Arcona) presenteras processer och IT-verktyg för taktisk planering inom bygg. I NCC:s fall har fokus legat på att skapa sammanhållna processer och IT-verktyg för att hämta in data om framtida projekt och aktivt välja rätt projekt baserat på vilka reseurs dessa kräver, vilken kapacitet man har tillgängliga när projektet startar och vad vinstmarginalen blir. I Arconas fall har fokus legat på att skapa sammanhållna processer och IT-verktyg för att balanser aktiviteter och materialbehov genom hela byggprojektet. På så sätt kan man i framtiden bättre planera behovet av kapacitet i deras nyutvecklade terminallösning baserat på hur mycket material som kan tänkas flöda genom den mht framtida projekt. Resultatet från studien visar på behovet av taktisk planering bland byggföretagen och hur den planeringen agerar som en länk mellan strategiska beslut och operativt arbete. Detta är ett viktigt bidrag för byggföretagen då de har beslutsstöd för att kunna fatta ett välgrundat beslut på vilka projekt man ska gå in med anbud på.
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