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- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
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| 3. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 4. |
- Bernal, Ximena E., et al.
(författare)
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Empowering Latina scientists
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Jönsson, Bengt, et al.
(författare)
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Priorities for health Economic Methodological Research: Results of an expert consultation
- 2017
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Ingår i: International Journal of Technology Assessment in Health Care. - : Cambridge University Press (CUP): HSS Journals. - 1471-6348 .- 0266-4623. ; 33:6, s. 609-619
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Tidskriftsartikel (refereegranskat)abstract
- Background: The importance of economic evaluation in decision making is growing with increasing budgetary pressures on health systems. Diverse economic evidence is available for a range of interventions across national contexts within Europe, but little attention has been given to identifying evidence gaps that, if filled, could contribute to more efficient allocation of resources. One objective of the Research Agenda for Health Economic Evaluation project is to determine the most important methodological evidence gaps for the ten highest burden conditions in the European Union (EU), and to suggest ways of filling these gaps. Methods: The highest burden conditions in the EU by Disability Adjusted Life Years were determined using the Global Burden of Disease study. Clinical interventions were identified for each condition based on published guidelines, and economic evaluations indexed in MEDLINE were mapped to each intervention. A panel of public health and health economics experts discussed the evidence during a workshop and identified evidence gaps. Results: The literature analysis contributed to identifying cross-cutting methodological and technical issues, which were considered by the expert panel to derive methodological research priorities. Conclusions: The panel suggests a research agenda for health economics which incorporates the use of real-world evidence in the assessment of new and existing interventions; increased understanding of cost-effectiveness according to patient characteristics beyond the -omics approach to inform both investment and disinvestment decisions; methods for assessment of complex interventions; improved cross-talk between economic evaluations from health and other sectors; early health technology assessment; and standardized, transferable approaches to economic modeling. © Cambridge University Press 2017.
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| 6. |
- Kirchhof, Paulus, et al.
(författare)
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Comprehensive risk reduction in patients with atrial fibrillation : emerging diagnostic and therapeutic options - a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference
- 2012
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 14:1, s. 8-27
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Forskningsöversikt (refereegranskat)abstract
- While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF.
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