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- Dewidar, O., et al.
(författare)
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Methodological guidance for incorporating equity when informing rapid-policy and guideline development
- 2022
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Ingår i: Journal of Clinical Epidemiology. - : Elsevier BV. - 0895-4356. ; 150, s. 142-153
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We provide guidance for considering equity in rapid reviews through examples of published COVID-19 rapid reviews. Study Design and Setting: This guidance was developed based on a series of methodological meetings, review of internationally renowned guidance such as the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for equity-focused systematic reviews (PRISMA-Equity) guideline. We identified Exemplar rapid reviews by searching COVID-19 databases and requesting examples from our team. Results: We proposed the following key steps: 1. involve relevant stakeholders with lived experience in the conduct and design of the review; 2. reflect on equity, inclusion and privilege in team values and composition; 3. develop research question to assess health inequities; 4. conduct searches in relevant disciplinary databases; 5. collect data and critically appraise recruitment, retention and attrition for populations experiencing inequities; 6. analyse evidence on equity; 7. evaluate the applicability of findings to populations experiencing inequities; and 8. adhere to reporting guidelines for communicating review findings. We illustrated these methods through rapid review examples. Conclusion: Implementing this guidance could contribute to improving equity considerations in rapid reviews produced in public health emergencies, and help policymakers better understand the distributional impact of diseases on the population.
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| 2. |
- Nitschke, S., et al.
(författare)
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Glycogen synthase downregulation rescues the amylopectinosis of murine RBCK1 deficiency
- 2022
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:7, s. 2361-2377
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Tidskriftsartikel (refereegranskat)abstract
- Longer glucan chains tend to precipitate. Glycogen, by far the largest mammalian glucan and the largest molecule in the cytosol with up to 55 000 glucoses, does not, due to a highly regularly branched spherical structure that allows it to be perfused with cytosol. Aberrant construction of glycogen leads it to precipitate, accumulate into polyglucosan bodies that resemble plant starch amylopectin and cause disease. This pathology, amylopectinosis, is caused by mutations in a series of single genes whose functions are under active study toward understanding the mechanisms of proper glycogen construction. Concurrently, we are characterizing the physicochemical particularities of glycogen and polyglucosans associated with each gene. These genes include GBE1, EPM2A and EPM2B, which respectively encode the glycogen branching enzyme, the glycogen phosphatase laforin and the laforin-interacting E3 ubiquitin ligase malin, for which an unequivocal function is not yet known. Mutations in GBE1 cause a motor neuron disease (adult polyglucosan body disease), and mutations in EPM2A or EPM2B a fatal progressive myoclonus epilepsy (Lafora disease). RBCK1 deficiency causes an amylopectinosis with fatal skeletal and cardiac myopathy (polyglucosan body myopathy 1, OMIM# 615895). RBCK1 is a component of the linear ubiquitin chain assembly complex, with unique functions including generating linear ubiquitin chains and ubiquitinating hydroxyl (versus canonical amine) residues, including of glycogen. In a mouse model we now show (i) that the amylopectinosis of RBCK1 deficiency, like in adult polyglucosan body disease and Lafora disease, affects the brain; (ii) that RBCK1 deficiency glycogen, like in adult polyglucosan body disease and Lafora disease, has overlong branches; (iii) that unlike adult polyglucosan body disease but like Lafora disease, RBCK1 deficiency glycogen is hyperphosphorylated; and finally (iv) that unlike laforin-deficient Lafora disease but like malin-deficient Lafora disease, RBCK1 deficiency's glycogen hyperphosphorylation is limited to precipitated polyglucosans. In summary, the fundamental glycogen pathology of RBCK1 deficiency recapitulates that of malin-deficient Lafora disease. Additionally, we uncover sex and genetic background effects in RBCK1 deficiency on organ-and brain-region specific amylopectinoses, and in the brain on consequent neuroinflammation and behavioural deficits. Finally, we exploit the portion of the basic glycogen pathology that is common to adult polyglucosan body disease, both forms of Lafora disease and RBCK1 deficiency, namely overlong branches, to show that a unified approach based on downregulating glycogen synthase, the enzyme that elongates glycogen branches, can rescue all four diseases.
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| 7. |
- Auffray, Charles, et al.
(författare)
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Making sense of big data in health research: Towards an EU action plan
- 2016
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Ingår i: Genome Medicine. - : BIOMED CENTRAL LTD. - 1756-994X. ; 8:71
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Tidskriftsartikel (refereegranskat)abstract
- Medicine and healthcare are undergoing profound changes. Whole-genome sequencing and high-resolution imaging technologies are key drivers of this rapid and crucial transformation. Technological innovation combined with automation and miniaturization has triggered an explosion in data production that will soon reach exabyte proportions. How are we going to deal with this exponential increase in data production? The potential of "big data" for improving health is enormous but, at the same time, we face a wide range of challenges to overcome urgently. Europe is very proud of its cultural diversity; however, exploitation of the data made available through advances in genomic medicine, imaging, and a wide range of mobile health applications or connected devices is hampered by numerous historical, technical, legal, and political barriers. European health systems and databases are diverse and fragmented. There is a lack of harmonization of data formats, processing, analysis, and data transfer, which leads to incompatibilities and lost opportunities. Legal frameworks for data sharing are evolving. Clinicians, researchers, and citizens need improved methods, tools, and training to generate, analyze, and query data effectively. Addressing these barriers will contribute to creating the European Single Market for health, which will improve health arid healthcare for all Europearis.
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| 9. |
- Jovanovic, Aleksandar, et al.
(författare)
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Tuning the electronic and chemisorption properties of hexagonal MgO nanotubes by doping - Theoretical study
- 2018
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Ingår i: Applied Surface Science. - : Elsevier. - 0169-4332 .- 1873-5584. ; 457, s. 1158-1166
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Tidskriftsartikel (refereegranskat)abstract
- Oxide materials offer a wide range of interesting physical and chemical properties. Even more versatile behavior of oxides is seen at the nanoscale, qualifying these materials for a number of applications. In this study we used DFT calculations to investigate the physical and chemical properties of small hexagonal MgO nanotubes of different length. We analyzed the effect of Li, B, C, N, and F doping on the properties of the nanotubes. We find that all dopants favor the edge positions when incorporated into the nanotubes. Doping results in the net magnetization whose value depends on the type of the impurity. Using the CO molecule as a probe, we studied the adsorption properties of pristine and doped MgO nanotubes. Our results show that the dopant sites are also the centers of significantly altered chemical reactivity. While pristine MgO nanotubes adsorb CO weakly, very strong adsorption at the dopant sites (B-, C-, and N-doped nanotubes) or neighboring edge atoms (F- and Li-doped nanotubes) is observed. Our results suggest that impurity engineering in oxide materials can be a promising strategy for the development of novel materials with possible use as selective adsorbents or catalysts.
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| 10. |
- Novcic, Katarina A., et al.
(författare)
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Theoretical analysis of doped graphene as cathode catalyst in Li-O-2 and Na-O-2 batteries - the impact of the computational scheme
- 2020
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Ingår i: Electrochimica Acta. - : Elsevier BV. - 0013-4686 .- 1873-3859. ; 354
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the reactions in M-O-2 cells (M = Li or Na) is of great importance for further advancement of this promising technology. Computational modelling can be helpful along this way, but an adequate approach is needed to model such complex systems. We propose a new scheme for modelling processes in M-O-2 cells, where reference energies are obtained from high-level theory, CCSD(T), while the interactions of reaction intermediates with catalyst surfaces are extracted from computationally less expensive DFT. The approach is demonstrated for the case of graphene-based surfaces as model catalysts in Li-O-2 and Na-O-2 cells using the minimum viable mechanism. B-doped graphene was identified as the best catalyst amongst considered surfaces, while pristine graphene performs poorly. Moreover, we show that the inclusion of dispersion corrections for DFT has a significant impact on calculated discharge and charge potentials and suggests that long-range dispersion interactions should always be considered when graphene-based materials are modelled as electrocatalysts. Finally, we offer general guidelines for designing new ORR catalysts for M-O-2 cells in terms of the optimization of the interactions of catalyst surface with reaction intermediates.
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