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- Caporale, N., et al.
(författare)
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From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375:6582
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Tidskriftsartikel (refereegranskat)abstract
- Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio, as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay. © 2022 American Association for the Advancement of Science. All rights reserved.
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| 4. |
- Freedman, Ben, et al.
(författare)
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Screening for Atrial Fibrillation A Report of the AF-SCREEN International Collaboration
- 2017
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Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 135:19, s. 1851-
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country-and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.
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- Rivard, Léna, et al.
(författare)
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Atrial Fibrillation and Dementia : A Report From the AF-SCREEN International Collaboration
- 2022
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Ingår i: Circulation. - 1524-4539. ; 145:5, s. 392-409
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Forskningsöversikt (refereegranskat)abstract
- Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia.
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| 6. |
- Wilden, A., et al.
(författare)
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Gamma-Radiolytic Stability of Solvents Containing C5-BPP (2,6-Bis(5-(2,2-dimethylpropyl)-1H-pyrazol-3-yl)pyridine) for Actinide(III)/Lanthanide(III) Separation
- 2016
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Ingår i: Solvent Extraction and Ion Exchange. - : Informa UK Limited. - 0736-6299 .- 1532-2262. ; 34:1, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- The stability of solvents containing the C5-BPP (2,6-Bis(5-(2,2-dimethylpropyl)-1H-pyrazol-3-yl)pyridine) extractant against gamma-irradiation up to 330 kGy adsorbed dose was evaluated using HPLC mass spectrometric and solvent extraction methods. The main radiolysis products were identified using high-resolution mass spectrometry. Quantitative analysis of the residual C5-BPP concentration in irradiated samples was accomplished by a specifically developed MRM (Multiple Reaction Monitoring) method. A mixture of C5-BPP with 2-bromohexanoic acid in kerosene and 1-octanol, which had been used in an actinide(III)/lanthanide(III) separation process demonstration test, was also studied for its radiolytic stability and a remarkable protective effect of the presence of nitric acid during irradiation was found.
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| 7. |
- Aneheim, Emma, 1982, et al.
(författare)
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Fission product interactions with nitrogen donor ligands used for spent nuclear fuel treatment
- 2013
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Ingår i: Polyhedron. - : Elsevier BV. - 0277-5387. ; 50:1, s. 154-163
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Tidskriftsartikel (refereegranskat)abstract
- The so called BTBP (bis-triazine bi-pyridine)-type molecules have been developed for liquid-liquid extraction in the advanced reprocessing of used nuclear fuel. One solvent composition that has proven to be promising for such an application is the combination of CyMe4-BTBP and tri-butyl phosphate (TBP) in cyclohexanone. This solvent can extract the actinides successfully but unfortunately some fission products are also co-extracted. One of the most problematic fission products is palladium, but silver and cadmium are also extracted by the proposed solvent, which has been investigated here. In this study it was found that CyMe4-BTBP in cyclohexanone, when extracting palladium from nitric acid, forms complexes that are soluble both in the organic and aqueous phase. The predominant complex observed in both phases established with mass spectrometry and confirmed by NMR is a 1:1 complex, contrary to silver that forms 2:2 complexes and cadmium that forms 1:2 complexes. The nitrate dependency of the palladium extraction from nitric acid into a BTBP containing organic phase was found to be two. However, with higher ionic strengths, such as under process conditions, the palladium was found to be salted out into the organic phase.
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| 8. |
- Brandes, Axel, et al.
(författare)
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Consumer-Led Screening for Atrial Fibrillation : Frontier Review of the AF-SCREEN International Collaboration
- 2022
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 146:19, s. 1461-1474
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Forskningsöversikt (refereegranskat)abstract
- The technological evolution and widespread availability of wearables and handheld ECG devices capable of screening for atrial fibrillation (AF), and their promotion directly to consumers, has focused attention of health care professionals and patient organizations on consumer-led AF screening. In this Frontiers review, members of the AF-SCREEN International Collaboration provide a critical appraisal of this rapidly evolving field to increase awareness of the complexities and uncertainties surrounding consumer-led AF screening. Although there are numerous commercially available devices directly marketed to consumers for AF monitoring and identification of unrecognized AF, health care professional-led randomized controlled studies using multiple ECG recordings or continuous ECG monitoring to detect AF have failed to demonstrate a significant reduction in stroke. Although it remains uncertain if consumer-led AF screening reduces stroke, it could increase early diagnosis of AF and facilitate an integrated approach, including appropriate anticoagulation, rate or rhythm management, and risk factor modification to reduce complications. Companies marketing AF screening devices should report the accuracy and performance of their products in high- and low-risk populations and avoid claims about clinical outcomes unless improvement is demonstrated in randomized clinical trials. Generally, the diagnostic yield of AF screening increases with the number, duration, and temporal dispersion of screening sessions, but the prognostic importance may be less than for AF detected by single-time point screening, which is largely permanent, persistent, or high-burden paroxysmal AF. Consumer-initiated ECG recordings suggesting possible AF always require confirmation by a health care professional experienced in ECG reading, whereas suspicion of AF on the basis of photoplethysmography must be confirmed with an ECG. Consumer-led AF screening is unlikely to be cost-effective for stroke prevention in the predominantly young, early adopters of this technology. Studies in older people at higher stroke risk are required to demonstrate both effectiveness and cost-effectiveness. The direct interaction between companies and consumers creates new regulatory gaps in relation to data privacy and the registration of consumer apps and devices. Although several barriers for optimal use of consumer-led screening exist, results of large, ongoing trials, powered to detect clinical outcomes, are required before health care professionals should support widespread adoption of consumer-led AF screening.
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| 9. |
- Börjesson, Anna E, et al.
(författare)
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Roles of transactivating functions 1 and 2 of estrogen receptor-alpha in bone.
- 2011
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 108:15, s. 6288-6293
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Tidskriftsartikel (refereegranskat)abstract
- The bone-sparing effect of estrogen is primarily mediated via estrogen receptor-α (ERα), which stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand binding domain. To evaluate the role of ERα AF-1 and ERα AF-2 for the effects of estrogen in bone in vivo, we analyzed mouse models lacking the entire ERα protein (ERα(-/-)), ERα AF-1 (ERαAF-1(0)), or ERα AF-2 (ERαAF-2(0)). Estradiol (E2) treatment increased the amount of both trabecular and cortical bone in ovariectomized (OVX) WT mice. Neither the trabecular nor the cortical bone responded to E2 treatment in OVX ERα(-/-) or OVX ERαAF-2(0) mice. OVX ERαAF-1(0) mice displayed a normal E2 response in cortical bone but no E2 response in trabecular bone. Although E2 treatment increased the uterine and liver weights and reduced the thymus weight in OVX WT mice, no effect was seen on these parameters in OVX ERα(-/-) or OVX ERαAF-2(0) mice. The effect of E2 in OVX ERαAF-1(0) mice was tissue-dependent, with no or weak E2 response on thymus and uterine weights but a normal response on liver weight. In conclusion, ERα AF-2 is required for the estrogenic effects on all parameters evaluated, whereas the role of ERα AF-1 is tissue-specific, with a crucial role in trabecular bone and uterus but not cortical bone. Selective ER modulators stimulating ERα with minimal activation of ERα AF-1 could retain beneficial actions in cortical bone, constituting 80% of the skeleton, while minimizing effects on reproductive organs.
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| 10. |
- Cooper, Steven J., et al.
(författare)
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Exploring Snowfall Variability through the High-Latitude Measurement of Snowfall (HiLaMS) Field Campaign
- 2022
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 103:8, s. E1762-E1780
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Tidskriftsartikel (refereegranskat)abstract
- The High-Latitude Measurement of Snowfall (HiLaMS) campaign explored variability in snowfall properties and processes at meteorologically distinct field sites located in Haukeliseter, Norway, and Kiruna, Sweden, during the winters of 2016/17 and 2017/18, respectively. Campaign activities were founded upon the sensitivities of a low-cost, core instrumentation suite consisting of Micro Rain Radar, Precipitation Imaging Package, and Multi-Angle Snow Camera. These instruments are highly portable to remote field sites and, considered together, provide a unique and complementary set of snowfall observations including snowflake habit, particle size distributions, fall speeds, surface snowfall accumulations, and vertical profiles of radar moments and snow water content. These snow-specific parameters, used in combination with existing observations from the field sites such as snow gauge accumulations and ambient weather conditions, allow for advanced studies of snowfall processes. HiLaMS observations were used to 1) successfully develop a combined radar and in situ microphysical property retrieval scheme to estimate both surface snowfall accumulation and the vertical profile of snow water content, 2) identify the predominant snowfall regimes at Haukeliseter and Kiruna and characterize associated macrophysical and microphysical properties, snowfall production, and meteorological conditions, and 3) identify biases in the HARMONIE-AROME numerical weather prediction model for forecasts of snowfall accumulations and vertical profiles of snow water content for the distinct snowfall regimes observed at the mountainous Haukeliseter site. HiLaMS activities and results suggest value in the deployment of this enhanced snow observing instrumentation suite to new and diverse high-latitude locations that may be underrepresented in climate and weather process studies.
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