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- Murari, A., et al.
(författare)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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- Sise, Andrew, et al.
(författare)
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Health and well-being needs of Indigenous adolescents : a protocol for a scoping review of qualitative studies
- 2024
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Improving the health of Indigenous adolescents is central to addressing the health inequities faced by Indigenous peoples. To achieve this, it is critical to understand what is needed from the perspectives of Indigenous adolescents themselves. There have been many qualitative studies that capture the perspectives of Indigenous young people, but synthesis of these has been limited to date.Methods and analysis: This scoping review seeks to understand the specific health needs and priorities of Indigenous adolescents aged 10-24 years captured via qualitative studies conducted across Australia, Aotearoa New Zealand, Canada, the USA, Greenland and Sami populations (Norway and Sweden). A team of Indigenous and non-Indigenous researchers from these nations will systematically search PubMed (including the MEDLINE, PubMed Central and Bookshelf databases), CINAHL, Embase, Scopus, the Informit Indigenous and Health Collections, Google Scholar, Arctic Health, the Circumpolar Health Bibliographic Database, Native Health Database, iPortal and NZresearch.org, as well as specific websites and clearinghouses within each nation for qualitative studies. We will limit our search to articles published in any language during the preceding 5 years given that needs may have changed significantly over time. Two independent reviewers will identify relevant articles using a two-step process, with disagreements resolved by a third reviewer and the wider research group. Data will then be extracted from included articles using a standardised form, with descriptive synthesis focussing on key needs and priorities. This scoping review will be conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.Ethics and dissemination: Ethics approval was not required for this review. Findings will be disseminated via a peer-reviewed journal article and will inform a broader international collaboration for Indigenous adolescent health to develop evidence-based actions and solutions.
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| 6. |
- Benson, Tyler W., et al.
(författare)
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Gut Microbiota-Derived Trimethylamine N-Oxide Contributes to Abdominal Aortic Aneurysm Through Inflammatory and Apoptotic Mechanisms
- 2023
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 147:14, s. 1079-1096
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Tidskriftsartikel (refereegranskat)abstract
- Background:Large-scale human and mechanistic mouse studies indicate a strong relationship between the microbiome-dependent metabolite trimethylamine N-oxide (TMAO) and several cardiometabolic diseases. This study aims to investigate the role of TMAO in the pathogenesis of abdominal aortic aneurysm (AAA) and target its parent microbes as a potential pharmacological intervention.Methods:TMAO and choline metabolites were examined in plasma samples, with associated clinical data, from 2 independent patient cohorts (N=2129 total). Mice were fed a high-choline diet and underwent 2 murine AAA models, angiotensin II infusion in low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice or topical porcine pancreatic elastase in C57BL/6J mice. Gut microbial production of TMAO was inhibited through broad-spectrum antibiotics, targeted inhibition of the gut microbial choline TMA lyase (CutC/D) with fluoromethylcholine, or the use of mice genetically deficient in flavin monooxygenase 3 (Fmo3(-/-)). Finally, RNA sequencing of in vitro human vascular smooth muscle cells and in vivo mouse aortas was used to investigate how TMAO affects AAA.Results:Elevated TMAO was associated with increased AAA incidence and growth in both patient cohorts studied. Dietary choline supplementation augmented plasma TMAO and aortic diameter in both mouse models of AAA, which was suppressed with poorly absorbed oral broad-spectrum antibiotics. Treatment with fluoromethylcholine ablated TMAO production, attenuated choline-augmented aneurysm initiation, and halted progression of an established aneurysm model. In addition, Fmo3(-/-) mice had reduced plasma TMAO and aortic diameters and were protected from AAA rupture compared with wild-type mice. RNA sequencing and functional analyses revealed choline supplementation in mice or TMAO treatment of human vascular smooth muscle cells-augmented gene pathways associated with the endoplasmic reticulum stress response, specifically the endoplasmic reticulum stress kinase PERK.Conclusions:These results define a role for gut microbiota-generated TMAO in AAA formation through upregulation of endoplasmic reticulum stress-related pathways in the aortic wall. In addition, inhibition of microbiome-derived TMAO may serve as a novel therapeutic approach for AAA treatment where none currently exist.
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| 7. |
- Gross, Sean M., et al.
(författare)
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A multi-omic analysis of MCF10A cells provides a resource for integrative assessment of ligand-mediated molecular and phenotypic responses
- 2022
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Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix proteins. While these signals are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understanding of the linkage between molecular and phenotypic changes, we generated a comprehensive dataset that catalogs the transcriptional, proteomic, epigenomic and phenotypic responses of MCF10A mammary epithelial cells after exposure to the ligands EGF, HGF, OSM, IFNG, TGFB and BMP2. Systematic assessment of the molecular and cellular phenotypes induced by these ligands comprise the LINCS Microenvironment (ME) perturbation dataset, which has been curated and made publicly available for community-wide analysis and development of novel computational methods ( synapse.org/LINCS_MCF10A ). In illustrative analyses, we demonstrate how this dataset can be used to discover functionally related molecular features linked to specific cellular phenotypes. Beyond these analyses, this dataset will serve as a resource for the broader scientific community to mine for biological insights, to compare signals carried across distinct molecular modalities, and to develop new computational methods for integrative data analysis.
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| 8. |
- Lee, Crystal, et al.
(författare)
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Association of anthropometry and weight change with risk of dementia and its major subtypes: a meta-analysis consisting 2.8 million adults with 57,294 cases of dementia
- 2020
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Ingår i: Obesity Reviews. - : Wiley. - 1467-7881 .- 1467-789X. ; 21:4
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Tidskriftsartikel (refereegranskat)abstract
- Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta-analysis. Compared with body mass index-defined lower-normal weight (18.5–22.4 kg/m2), the risk of all-cause dementia was higher among underweight individuals but lower among those with upper-normal (22.5–24.9 kg/m2) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had non-significant higher vascular dementia risk. Weight loss was associated with higher all-cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change and dementia is complex and exhibits nonlinear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative.
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- Lee, Crystal Man Ying, et al.
(författare)
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Comparing different definitions of prediabetes with subsequent risk of diabetes: an individual participant data meta-analysis involving 76 513 individuals and 8208 cases of incident diabetes.
- 2019
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Ingår i: BMJ open diabetes research & care. - : BMJ. - 2052-4897. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- There are currently five widely used definition of prediabetes. We compared the ability of these to predict 5-year conversion to diabetes and investigated whether there were other cut-points identifying risk of progression to diabetes that may be more useful.We conducted an individual participant meta-analysis using longitudinal data included in the Obesity, Diabetes and Cardiovascular Disease Collaboration. Cox regression models were used to obtain study-specific HRs for incident diabetes associated with each prediabetes definition. Harrell's C-statistics were used to estimate how well each prediabetes definition discriminated 5-year risk of diabetes. Spline and receiver operating characteristic curve (ROC) analyses were used to identify alternative cut-points.Sixteen studies, with 76513 participants and 8208 incident diabetes cases, were available. Compared with normoglycemia, current prediabetes definitions were associated with four to eight times higher diabetes risk (HRs (95% CIs): 3.78 (3.11 to 4.60) to 8.36 (4.88 to 14.33)) and all definitions discriminated 5-year diabetes risk with good accuracy (C-statistics 0.79-0.81). Cut-points identified through spline analysis were fasting plasma glucose (FPG) 5.1mmol/L and glycated hemoglobin (HbA1c) 5.0% (31 mmol/mol) and cut-points identified through ROC analysis were FPG 5.6mmol/L, 2-hour postload glucose 7.0mmol/L and HbA1c 5.6% (38 mmol/mol).In terms of identifying individuals at greatest risk of developing diabetes within 5years, using prediabetes definitions that have lower values produced non-significant gain. Therefore, deciding which definition to use will ultimately depend on the goal for identifying individuals at risk of diabetes.
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| 10. |
- Lee, Crystal Man Ying, et al.
(författare)
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Comparison of relationships between four common anthropometric measures and incident diabetes
- 2017
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 132, s. 36-44
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Tidskriftsartikel (refereegranskat)abstract
- Aims: First, to conduct a detailed exploration of the prospective relations between four commonly used anthropometric measures with incident diabetes and to examine their consistency across different population subgroups. Second, to compare the ability of each of the measures to predict five-year risk of diabetes. Methods: We conducted a meta- analysis of individual participant data on body mass index (BMI), waist circumference (WC), waist- hip and waist- height ratio (WHtR) from the Obesity, Diabetes and Cardiovascular Disease Collaboration. Cox proportional hazard models were used to estimate the association between a one standard deviation increment in each anthropometric measure and incident diabetes. Harrell's concordance statistic was used to test the predictive accuracy of each measure for diabetes risk at five years. Results: Twenty- one studies with 154,998 participants and 9342 cases of incident diabetes were available. Each of the measures had a positive association with incident diabetes. A one standard deviation increment in each of the measures was associated with 64- 80% higher diabetes risk. WC and WHtR more strongly associated with risk than BMI (ratio of hazard ratios: 0.95 [0.92,0.99] - 0.97 [0.95,0.98]) but there was no appreciable difference between the four measures in the predictive accuracy for diabetes at five years. Conclusions: Despite suggestions that abdominal measures of obesity have stronger associations with incident diabetes and better predictive accuracy than BMI, we found no overall advantage in any one measure at discriminating the risk of developing diabetes. Any of these measures would suffice to assist in primary diabetes prevention efforts.
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