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  • Kanai, M, et al. (författare)
  • 2023
  • swepub:Mat__t
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  • Leong, C, et al. (författare)
  • Psychotropic Medication Use Before and During COVID-19: A Population-Wide Study
  • 2022
  • Ingår i: Frontiers in pharmacology. - : Frontiers Media SA. - 1663-9812. ; 13, s. 886652-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The coronavirus disease 2019 (COVID-19) pandemic and public health measures that took place have led to concerns regarding mental health and receipt of psychotropic medications. We aimed to study the changes in psychotropic medication dispensation rates before and during the COVID-19 pandemic in the general population.Methods: Administrative health data from the Canadian province of Manitoba was used to describe the quarterly incidence and prevalence of antipsychotics, antidepressants, and anxiolytic/sedative-hypnotics from January 1, 2015 to December 31, 2020. Individuals who received at least one prescription within each quarter were considered exposed to the medication. The denominator was the total population within each quarter. Incidence was defined as no receipt of medication in the 3 years prior to the quarter of interest. Autoregression models for time series data plus indicator variables were used to compare each quarter of 2020 after public health measures were implemented in March 2020 in relation to the expected trend. Analyses were stratified by age and sex.Results: There were 1,394,885 individuals in the first quarter of 2020, with a mean (SD) age of 38.9 (23.4) years, 50.3% were female, and 36.1% had a psychiatric diagnosis in the previous 5 years. A significant decrease was observed for incident antidepressant use (p < 0.05 for both sexes and all age groups except for those 65 years and older) and anxiolytic use (p < 0.05 for both sexes and all age groups except 80 years and older) in the second quarter (April-June) of 2020 compared to the expected trend. Females and those aged 40 years and older had a significantly higher incidence of antidepressant and antipsychotic use in the final quarter of 2020 compared to the expected trend (p < 0.05).Conclusion: Our findings indicate a decrease in new prescriptions for antidepressants and anxiolytics in the 3 months after COVID-19 in-person restrictions were first implemented. We then observed an increase in the new use of antidepressants and antipsychotics at the end of 2020, in females and people aged 40 years and older, with the highest rates of use in the population 80 years and older.
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  • Petkevicius, K., et al. (författare)
  • TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis
  • 2022
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The regulation of cellular phosphatidylethanolamine (PE) acyl chain composition is poorly understood. Here, the authors show that TLCD1 and TLCD2 proteins mediate the formation of monounsaturated fatty acid-containing PE species and promote the progression of non-alcoholic steatohepatitis. The fatty acid composition of phosphatidylethanolamine (PE) determines cellular metabolism, oxidative stress, and inflammation. However, our understanding of how cells regulate PE composition is limited. Here, we identify a genetic locus on mouse chromosome 11, containing two poorly characterized genes Tlcd1 and Tlcd2, that strongly influences PE composition. We generated Tlcd1/2 double-knockout (DKO) mice and found that they have reduced levels of hepatic monounsaturated fatty acid (MUFA)-containing PE species. Mechanistically, TLCD1/2 proteins act cell intrinsically to promote the incorporation of MUFAs into PEs. Furthermore, TLCD1/2 interact with the mitochondria in an evolutionarily conserved manner and regulate mitochondrial PE composition. Lastly, we demonstrate the biological relevance of our findings in dietary models of metabolic disease, where Tlcd1/2 DKO mice display attenuated development of non-alcoholic steatohepatitis compared to controls. Overall, we identify TLCD1/2 proteins as key regulators of cellular PE composition, with our findings having broad implications in understanding and treating disease.
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  • Scheffle, M., et al. (författare)
  • Low cost large area panel processing of MCM-D substrates and packages
  • 2001
  • Ingår i: Proceedings of IPACK’01. ; , s. -8
  • Konferensbidrag (refereegranskat)abstract
    • The paper describes the results of the EU research project LAP that had the target to develop and to demonstrate a low-cost high-density substrate manufacturing technology for 1st-level die assemblies. The cost target of 1€€/in2 had to be obtained by increasing toady’s 4x4in2 panel sizes to panels upto 24x24in2. The results focus on RF characterization (integrated antennas up to 83GHz, inductors up a Q value of 50), novel packaging strategies (integration of substrate and package), and cost achievements (approaching the cost target). The technology capabilities have been demonstrated with a 9:4 satellite switch operating up to 2.4GHz and readout electronics for physics experiments.
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  • Aboulatta, L, et al. (författare)
  • Preterm birth and stillbirth rates associated with socioeconomic disparities during COVID-19 pandemic: a population-based cross-sectional study
  • 2023
  • Ingår i: BMJ paediatrics open. - : BMJ. - 2399-9772. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Conflicting evidence exists on the impact of the COVID-19 pandemic restrictions on preterm birth (PTB) and stillbirth rates. We aimed to evaluate changes in PTB and stillbirth rates before and during the pandemic period and assess the potential effect modification of socioeconomic status (SES).MethodsUsing the linked administrative health databases from Manitoba, Canada, we conducted a cross-sectional study among all pregnant women, comparing 3.5 years pre-pandemic (1 October 2016 to 29 February 2020) to the first year of the pandemic (1 March 2020 to 31 March 2021). We used generalised linear models to assess the quarterly rates of PTB (<37 weeks) and stillbirths. We calculated the predicted trends based on pre-pandemic period data. Finally, we evaluated the PTB and stillbirth rates among lower and higher SES pregnant women (average annual household income) using subgroup analysis and interaction models.ResultsWe examined 70 931 pregnancies in Manitoba during the study period. The risk of PTB increased by 7.7% (95%CI 1.01 to 1.13) and stillbirths by 33% (95% CI 1.08 to 1.64) during the pandemic period. Following COVID-19 restrictions implemented in March 2020, there were increases in the quarterly rates of both PTB (immediate increase (β2)=1.37; p=0.0247) and stillbirths (immediate increase (β2)=0.12; p=0.4434). Among the lower income groups, the pandemic restrictions resulted in an immediate relative increase in PTB and stillbirth rates by 20.12% (immediate increase (β2)=3.17; p=0.0057) and 27.19% (immediate increase (β2)=0.48; p=0.0852). However, over the pandemic, the overall PTB rate significantly decreased as a rebound effect by 0.85% per quarter (p=0.0004), whereas the overall stillbirth rate did not decrease significantly (slope decrease (β3) =−0.01; p=0.8296) compared with the pre-pandemic period. The quarterly rates during the pandemic among the higher income group decreased by 0.39% (p=0.1296) for PTB and increased by 0.07% (p=0.1565) for stillbirth. We observed an effect modification by SES for PTB rates (p=0.047).ConclusionWhile the onset of COVID-19 pandemic restrictions was not associated with significant effects on stillbirth rates, we observed an immediate and rebound effect on PTB rates. The impact of COVID-19 on preterm birth was dependent on SES, with higher influence on families with lower SES. Further studies are needed to detect future trend changes during pandemic waves after 2021 and assess potential underlying mechanisms.
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  • Shouman, W, et al. (författare)
  • Trends of Utilization of Antiseizure Medications Among Pregnant Women in Manitoba, Canada: A 20-Year Population-Based Study
  • 2022
  • Ingår i: Frontiers in pharmacology. - : Frontiers Media SA. - 1663-9812. ; 13, s. 871136-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Evidence from developed countries demonstrates that the use of antiseizure medications (ASMs) has been increasing in the last decade. Pregnant women have a very challenging risk benefit trade-off in terms of ASM utilization, and it is crucial to know if increased utilization is seen among pregnant women.Objective: To examine time-trends of utilization of ASM therapies among pregnant women in Manitoba, Canada.Methods: We conducted a population-based cohort study using de-identified, linked administrative databases from Manitoba. Pregnancies between 1995 and 2018 were included. Four groups of pregnant people were created based on ASM exposure and epilepsy diagnosis.Results: Of 273,492 pregnancies, 812 (3/1000) had epilepsy diagnosis and were exposed to ASMs, 963 (3.5/1000) had epilepsy diagnosis and were unexposed, and 2742 (10/1000) were exposed to ASMs and did not have epilepsy diagnosis. Overall, the number of pregnancies exposed to ASMs increased significantly from 0.56% in 1997 to 2.21% in 2018 (p &lt; 0.0001). Subgroup analysis by epilepsy diagnosis showed no significant change in ASMs exposure among pregnant women with epilepsy [the proportion of women exposed to ASM from all pregnancies was 0.37% (in 1997) and 0.36% (in 2018), p = 0.24]. A drop in carbamazepine use was observed, while the number of lamotrigine prescriptions increased from 6.45% in 1997 to 52% by 2018. ASM use among pregnant women without epilepsy increased significantly from 0.19% in 1997 to 1.85% in 2018 (p &lt; 0.0001). In the total cohort of pregnancies, 1439 (0.53%) were exposed during their entire pregnancy, and 1369 (0.5%) were exposed only in their first trimester. Clonazepam was the most used ASM during the study period (1953 users, 0.71%), followed by gabapentin (785 users, 0.29%) and carbamazepine (449 users, 0.16%).Conclusion: No major shifts in the quantity of ASM use over the study period were observed among pregnant women with epilepsy. However, there was a significant increase in ASM use among pregnant women without epilepsy. The study results warrant further investigation into the implications of ASM use in pregnancy for indications other than epilepsy.
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  • Behnen, Petra, et al. (författare)
  • Calcium-Dependent Interaction of Calmodulin with Human 80S Ribosomes and Polyribosomes.
  • 2012
  • Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 51:34, s. 6718-6727
  • Tidskriftsartikel (refereegranskat)abstract
    • Ribosomes are the protein factories of every living cell. The process of protein translation is highly complex and tightly regulated by a large number of diverse RNAs and proteins. Earlier studies indicate that Ca(2+) plays a role in protein translation. Calmodulin (CaM), a ubiquitous Ca(2+)-binding protein, regulates a large number of proteins participating in many signaling pathways. Several 40S and 60S ribosomal proteins have been identified to interact with CaM, and here, we report that CaM binds with high affinity to 80S ribosomes and polyribosomes in a Ca(2+)-dependent manner. No binding is observed in buffer with 6 mM Mg(2+) and 1 mM EGTA that chelates Ca(2+), suggesting high specificity of the CaM-ribosome interaction dependent on the Ca(2+) induced conformational change of CaM. The interactions between CaM and ribosomes are inhibited by synthetic peptides comprising putative CaM-binding sites in ribosomal proteins S2 and L14. Using a cell-free in vitro translation system, we further found that these synthetic peptides are potent inhibitors of protein synthesis. Our results identify an involvement of CaM in the translational activity of ribosomes.
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  • Fargevieille, Amélie, et al. (författare)
  • Propagule size and sex ratio influence colonisation dynamics after introduction of a non-native lizard
  • 2022
  • Ingår i: Journal of Animal Ecology. - : Wiley. - 0021-8790 .- 1365-2656. ; 91:4, s. 845-857
  • Tidskriftsartikel (refereegranskat)abstract
    • The composition of founding populations plays an important role in colonisation dynamics and can influence population growth during early stages of biological invasion. Specifically, founding populations with small propagules (i.e. low number of founders) are vulnerable to the Allee effect and have reduced likelihood of establishment compared to those with large propagules. The founding sex ratio can also impact establishment via its influence on mating success and offspring production.Our goal was to test the effects of propagule size and sex ratio on offspring production and annual population growth following introductions of a non-native lizard species (Anolis sagrei). We manipulated propagule composition on nine small islands, then examined offspring production, population growth and survival rate of founders and their descendants encompassing three generations.By the third reproductive season, per capita offspring production was higher on islands seeded with a relatively large propagule size, but population growth was not associated with propagule size. Propagule sex ratio did not affect offspring production, but populations with a female-biased propagule had positive growth, whereas those with a male-biased propagule had negative growth in the first year. Populations were not affected by propagule sex ratio in subsequent years, possibly due to rapid shifts towards balanced (or slightly female biased) population sex ratios.Overall, we show that different components of population fitness have different responses to propagule size and sex ratio in ways that could affect early stages of biological invasion. Despite these effects, the short life span and high fecundity of A. sagrei likely helped small populations to overcome Allee effects and enabled all populations to successfully establish.Our rare experimental manipulation of propagule size and sex ratio can inform predictions of colonisation dynamics in response to different compositions of founding populations, which is critical in the context of population ecology and invasion dynamics.
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  • Hines, Delaney, et al. (författare)
  • Scoping review shows wide variation in the definitions of bronchopulmonary dysplasia in preterm infants and calls for a consensus
  • 2017
  • Ingår i: Acta Paediatrica. - : Wiley-Blackwell. - 0803-5253 .- 1651-2227. ; 106:3, s. 366-374
  • Tidskriftsartikel (refereegranskat)abstract
    • The use of different definitions for bronchopulmonary dysplasia (BPD) has been an ongoing challenge. We searched papers published in English from 2010 and 2015 reporting BPD as an outcome, together with studies that compared BPD definitions between 1978 and 2015. We found that the incidence of BPD ranged from 6% to 57%, depending on the definition chosen, and that studies that investigated correlations with long-term pulmonary and/or neurosensory outcomes reported moderate-to-low predictive values regardless of the BPD criteria.CONCLUSION: A comprehensive and evidence-based definition for BPD needs to be developed for benchmarking and prognostic use.
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  • Pälike, Heiko, et al. (författare)
  • A Cenozoic record of the equatorial Pacific carbonate compensation depth
  • 2012
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 488:7413, s. 609-614
  • Tidskriftsartikel (refereegranskat)abstract
    • Atmospheric carbon dioxide concentrations and climate are regulated on geological timescales by the balance between carbon input from volcanic and metamorphic outgassing and its removal by weathering feedbacks; these feedbacks involve the erosion of silicate rocks and organic-carbon-bearing rocks. The integrated effect of these processes is reflected in the calcium carbonate compensation depth, which is the oceanic depth at which calcium carbonate is dissolved. Here we present a carbonate accumulation record that covers the past 53 million years from a depth transect in the equatorial Pacific Ocean. The carbonate compensation depth tracks long-term ocean cooling, deepening from 3.0-3.5 kilometres during the early Cenozoic (approximately 55 million years ago) to 4.6 kilometres at present, consistent with an overall Cenozoic increase in weathering. We find large superimposed fluctuations in carbonate compensation depth during the middle and late Eocene. Using Earth system models, we identify changes in weathering and the mode of organic-carbon delivery as two key processes to explain these large-scale Eocene fluctuations of the carbonate compensation depth.
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