| 1. |
- Bousquet, Jean, et al.
(författare)
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Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879
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Tidskriftsartikel (refereegranskat)abstract
- Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
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| 2. |
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| 3. |
- Menditto, Enrica, et al.
(författare)
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Adherence to treatment in allergic rhinitis using mobile technology : The MASK Study
- 2019
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Ingår i: Clinical and Experimental Allergy. - : WILEY. - 0954-7894 .- 1365-2222. ; 49:4, s. 442-460
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. Results: A total of 12143 users were registered. A total of 6949 users reported at least one VAS data recording. Among them, 1887 users reported >= 7 VAS data. About 1195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR >= 70% and PDC <= 1.25), 51 (4.23%) were partly adherent (MPR >= 70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR <70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users. Conclusion and clinical relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.
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| 4. |
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| 5. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Micah, Angela E., et al.
(författare)
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Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
- 2021
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
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Forskningsöversikt (refereegranskat)abstract
- Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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| 10. |
- Bousquet, Jean, et al.
(författare)
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ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
- 2021
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
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Forskningsöversikt (refereegranskat)abstract
- Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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| 11. |
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| 13. |
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| 14. |
- Stephen, D, et al.
(författare)
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Continental-scale patterns of nutrient and fish effects on shallow lakes: introduction to a pan-European mesocosm experiment
- 2004
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Ingår i: Freshwater Biology. - : Wiley. - 0046-5070 .- 1365-2427. ; 49:12, s. 1517-1524
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Tidskriftsartikel (refereegranskat)abstract
- 1. Shallow lake ecosystems are normally dominated by submerged and emergent plants. Biological stabilising mechanisms help preserve this dominance. The systems may switch to dominance by phytoplankton, however, with loss of submerged plants. This process usually takes place against a background of increasing nutrient loadings but also requires additional switch mechanisms, which damage the plants or interfere with their stabilising mechanisms. 2. The extent to which the details or even major features of this general model may change with geographical location are not clear. Manipulation of the fish community (biomanipulation) has often been used to clear the water of algae and restore the aquatic plants in northerly locations, but it is again not clear whether this is equally appropriate at lower latitudes. 3. Eleven parallel experiments (collectively the International Mesocosm Experiment, IME) were carried out in six lakes in Finland, Sweden, England, the Netherlands and Spain in 1998 and 1999 to investigate the between-year and large-scale spatial variation in relationships between nutrient loading and zooplanktivorous fish on submerged plant and plankton communities in shallow lakes. 4. Comparability of experiments in different locations was achieved to a high degree. Cross-laboratory comparisons of chemical analyses revealed some systematic differences between laboratories. These are unlikely to lead to major misinterpretations. 5. Nutrient addition, overall, had its greatest effect on water chemistry then substantial effects on phytoplankton and zooplankton. Fish addition had its major effect on zooplankton and did not systematically change the water chemistry. There was no trend in the relative importance of fish effects with latitude, but nutrient addition affected more variables with decreasing latitude. 6. The relative importance of top-down and bottom-up influences on the plankton differed in different locations and between years at the same location. The outcome of the experiments in different years was more predictable with decreasing latitude and this was attributed to more variable weather at higher latitudes that created more variable starting conditions for the experiments.
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| 15. |
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| 16. |
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| 17. |
- Landolfo, C., et al.
(författare)
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Benign descriptors and ADNEX in two-step strategy to estimate risk of malignancy in ovarian tumors : retrospective validation on IOTA 5 multicenter cohort
- 2023
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Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 61:2, s. 231-242
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Previous work suggested that the ultrasound-based benign Simple Descriptors can reliably exclude malignancy in a large proportion of women presenting with an adnexal mass. We aim to validate a modified version of the Benign Simple Descriptors (BD), and we introduce a two-step strategy to estimate the risk of malignancy: if the BDs do not apply, the ADNEX model is used to estimate the risk of malignancy. Methods: This is a retrospective analysis using the data from the 2-year interim analysis of the IOTA5 study, in which consecutive patients with at least one adnexal mass were recruited irrespective of subsequent management (conservative or surgery). The main outcome was classification of tumors as benign or malignant, based on histology or on clinical and ultrasound information during one year of follow-up. Multiple imputation was used when outcome based on follow-up was uncertain according to predefined criteria. Results: 8519 patients were recruited at 36 centers between 2012 and 2015. We included all masses that were not already in follow-up at recruitment from 17 centers with good quality surgical and follow-up data, leaving 4905 patients for statistical analysis. 3441 (70%) tumors were benign, 978 (20%) malignant, and 486 (10%) uncertain. The BDs were applicable in 1798/4905 (37%) tumors, and 1786 (99.3%) of these were benign. The two-step strategy based on ADNEX without CA125 had an area under the receiver operating characteristic curve (AUC) of 0.94 (95% CI, 0.91-0.95). The risk of malignancy was slightly underestimated, but calibration varied between centers. A sensitivity analysis in which we expanded the definition of uncertain outcome resulted in 1419 (29%) tumors with uncertain outcome and an AUC of the two-step strategy without CA125 of 0.93 (95% CI, 0.91-0.95). Conclusion: A large proportion of adnexal masses can be classified as benign by the BDs. For the remaining masses the ADNEX model can be used to estimate the risk of malignancy. This two-step strategy is convenient for clinical use.
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| 18. |
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| 19. |
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| 20. |
- Moss, B, et al.
(författare)
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Continental-scale patterns of nutrient and fish effects on shallow lakes: synthesis of a pan-European mesocosm experiment
- 2004
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Ingår i: Freshwater Biology. - : Wiley. - 0046-5070 .- 1365-2427. ; 49:12, s. 1633-1649
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Tidskriftsartikel (refereegranskat)abstract
- 1. Results are analysed from 11 experiments in which effects of fish addition and nutrient loading on shallow lakes were studied in mesocosms. The experiments, five in 1998, six in 1999, were carried out in six lakes, distributed from Finland to southern Spain, according to a standard protocol. 2. Effects of the treatments on 29 standard chemical, phytoplankton and zooplankton variables are examined to assess the relative importance of bottom-up (nutrient enrichment) and top-down (fish predation) effects. For each year, the experiments in different locations are treated as replicates in a meta-analysis. Results of individual experiments are then compared in terms of the patterns of significant influences of nutrient addition and fish predation with these overall results (the baseline), and between years in the same location. 3. The overall meta-analysis gave consistent results across the 2 years, with nutrient loading influencing all of the chemical variables, and on average 31% of primary producer and 39% of zooplankton variables. In contrast, fish influenced none of the chemical variables, 11% of the primary producer and 44% of the zooplankton variables. Nutrient effects on the system were thus about three times greater than fish effects, although fish effects were not inconsiderable. 4. The relative importance of nutrients and fish in individual experiments often differed between years at the same location and effects deviated to varying degrees from the baseline. These deviations were treated as measures of consistency (predictability) of conclusions in repeat experiments. Consistency increased southwards and this is interpreted as a consequence of more variable annual weather northwards. 5. The influence of nutrient loading was greater southwards and this was probably manifested through naturally greater annual macrophyte abundance in warmer locations in consequence of the longer plant growing-season. There was no trend in the relative importance of fish effects with latitude but this may partly be an artefact of the simple fish community used. These findings suggest that nutrient control should be a greater priority than biomanipulation in the restoration of eutrophicated shallow lakes in warm temperate regions. 6. Starting conditions affected the outcome of experiments. High initial concentrations of total phosphorus and planktonic chlorophyll a concentration (created by local conditions prior to the experiment) led to de-emphasis of the importance of nutrient loading in the experiment.
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| 21. |
- Ostaszewski, Marek, et al.
(författare)
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COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms
- 2021
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Ingår i: Molecular Systems Biology. - : John Wiley & Sons. - 1744-4292 .- 1744-4292. ; 17:10
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Tidskriftsartikel (refereegranskat)abstract
- We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective.
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| 22. |
- Rocha, W. R.M., et al.
(författare)
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JWST Observations of Young protoStars (JOYS+): Detecting icy complex organic molecules and ions: I. CH4, SO2, HCOO, OCN, H2CO, HCOOH, CH3CH2OH, CH3CHO, CH3OCHO, and CH3COOH
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 683
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Tidskriftsartikel (refereegranskat)abstract
- Context. Complex organic molecules (COMs) are ubiquitously detected in the gas phase and thought to be mostly formed on icy grains. Nevertheless, there have not been any unambiguous detections of COMs larger than CH3OH in ices reported thus far. Exploring this matter in greater detail has now become possible with the unprecedented possibilities offered by the James Webb Space Telescope (JWST) within the infrared (IR) spectral range with its very high sensitivity and spectral resolution in the critical 5 10 μm range, the fingerprint region of oxygen-bearing COMs. Aims. In the JWST Observations of Young protoStars (JOYS+) program, more than 30 protostars are undergoing observation with the Medium Resolution Spectrograph (MRS) of the Mid-IR Instrument (MIRI). The goal of this study is to comprehensively explore the COMs ice signatures in one low- and one high-mass protostar: NGC 1333 IRAS 2A and IRAS 23385+6053, respectively. Methods. We performed global continuum and silicate subtractions of the MIRI-MRS spectra, followed by a local continuum subtraction in optical depth scale in the range around 6.8 and 8.6 μm, the ice COM fingerprint region. We explored different choices for the local continuum and silicate subtraction. Next, we fit the observational data with a large sample of available IR laboratory ice spectra. We used the ENIIGMA fitting tool, a genetic algorithm-based code that not only finds the best fit between the lab data and the observations, but also performs a statistical analysis of the solutions, such as deriving the confidence intervals and quantifying fit degeneracy. Results. We report the best fits for the spectral ranges between 6.8 and 8.6 μm in NGC 1333 IRAS 2A and IRAS 23385+6053, originating from simple molecules and COMs, as well as negative ions. Overall, we find that ten chemical species are needed to reproduce the astronomical data. The strongest feature in this range (7.7 μm) is dominated by CH4, with contributions from SO2 and OCN. Our results indicate that the 7.2 and 7.4 μm bands are mostly dominated by HCOO. We also find statistically robust detections of COMs based on multiple bands, most notably, CH3CHO, CH3CH2OH, and CH3OCHO. We also report a likely detection of CH3COOH. Based on the ice column density ratios between CH3CH2OH and CH3CHO of NGC 1333 IRAS 2A and IRAS 23385+6053, we find compelling evidence that these COMs are formed on icy grains. Finally, the derived ice abundances for NGC 1333 IRAS 2A correlate well with those in comet 67P/GC within a factor of 5. Conclusions. Based on the high-quality JWST (MIRI-MRS) spectra, we conclude that COMs are present in interstellar ices, thus providing additional proof for the solid-state origin of these species in star-forming regions. In addition, the good correlation between the ice abundances in comet 67P and NGC 1333 IRAS 2A is fully in line with the idea that cometary COMs may be inherited from the early protostellar phases to a significant extent.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Thompson, B.A., et al.
(författare)
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Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:2, s. 107-115
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Tidskriftsartikel (refereegranskat)abstract
- The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and apply a standardized classification scheme to constitutional variants in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2. Unpublished data submission was encouraged to assist in variant classification and was recognized through microattribution. The scheme was refined by multidisciplinary expert committee review of the clinical and functional data available for variants, applied to 2,360 sequence alterations, and disseminated online. Assessment using validated criteria altered classifications for 66% of 12,006 database entries. Clinical recommendations based on transparent evaluation are now possible for 1,370 variants that were not obviously protein truncating from nomenclature. This large-scale endeavor will facilitate the consistent management of families suspected to have Lynch syndrome and demonstrates the value of multidisciplinary collaboration in the curation and classification of variants in public locus-specific databases. © 2014 Nature America, Inc.
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| 27. |
- Van de Bund, WJ, et al.
(författare)
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Responses of phytoplankton to fish predation and nutrient loading in shallow lakes: a pan-European mesocosm experiment
- 2004
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Ingår i: Freshwater Biology. - : Wiley. - 0046-5070 .- 1365-2427. ; 49:12, s. 1608-1618
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Tidskriftsartikel (refereegranskat)abstract
- 1. The impacts of nutrients (phosphorus and nitrogen) and planktivorous fish on phytoplankton composition and biomass were studied in six shallow, macrophyte-dominated lakes across Europe using mesocosm experiments. 2. Phytoplankton biomass was more influenced by nutrients than by densities of planktivorous fish. Nutrient addition resulted in increased algal biomass at all locations. In some experiments, a decrease was noted at the highest nutrient loadings, corresponding to added concentrations of 1 mg L-1 P and 10 mg L-1 N. 3. Chlorophyll a was a more precise parameter to quantify phytoplankton biomass than algal biovolume, with lower within-treatment variability. 4. Higher densities of planktivorous fish shifted phytoplankton composition toward smaller algae (GALD < 50 mum). High nutrient loadings selected in favour of chlorophytes and cyanobacteria, while biovolumes of diatoms and dinophytes decreased. High temperatures also may increase the contribution of cyanobacteria to total phytoplankton biovolume in shallow lakes.
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| 28. |
- Bedard, Annabelle, et al.
(författare)
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Mobile technology offers novel insights into the control and treatment of allergic rhinitis : The MASK study
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 144:1, s. 135-143
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mobile health can be used to generate innovative insights into optimizing treatment to improve allergic rhinitis (AR) control. Objectives: A cross-sectional real-world observational study was undertaken in 22 countries to complement a pilot study and provide novel information on medication use, disease control, and work productivity in the everyday life of patients with AR. Methods: A mobile phone app (Allergy Diary, which is freely available on Google Play and Apple stores) was used to collect the data of daily visual analogue scale (VAS) scores for (1) overall allergic symptoms; (2) nasal, ocular, and asthma symptoms; (3) work; and (4) medication use by using a treatment scroll list including all allergy medications (prescribed and over-the-counter) customized for 22 countries. The 4 most common intranasal medications containing intranasal corticosteroids and 8 oral H-1-antihistamines were studied. Results: Nine thousand one hundred twenty-two users filled in 112,054 days of VASs in 2016 and 2017. Assessment of days was informative. Control of days with rhinitis differed between no (best control), single (good control for intranasal corticosteroid-treated days), or multiple (worst control) treatments. Users with the worst control increased the range of treatments being used. The same trend was found for asthma, eye symptoms, and work productivity. Differences between oral H-1-antihistamines were found. Conclusions: This study confirms the usefulness of the Allergy Diary in accessing and assessing behavior in patients with AR. This observational study using a very simple assessment tool (VAS) on a mobile phone had the potential to answer questions previously thought infeasible.
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| 29. |
- Bousquet, J. Jean, et al.
(författare)
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Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
- 2019
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Ingår i: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
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Forskningsöversikt (refereegranskat)abstract
- Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care.Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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| 30. |
- Connolly, S., et al.
(författare)
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Rationale and design of ACTIVE: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events
- 2006
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Ingår i: American heart journal. - 1097-6744. ; 151:6, s. 1187-93
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Atrial fibrillation (AF) is the most frequently occurring cardiac arrhythmia with often serious clinical consequences. Many patients have contraindications to anticoagulation, and it is often underused in clinical practice. The addition of clopidogrel to aspirin (ASA) has been shown to reduce vascular events in a number of high-risk populations. Irbesartan is an angiotensin receptor-blocking agent that reduces blood pressure and has other vascular protective effects. METHODS AND RESULTS: ACTIVE W is a noninferiority trial of clopidogrel plus ASA versus oral anticoagulation in patients with AF and at least 1 risk factor for stroke. ACTIVE A is a double-blind, placebo-controlled trial of clopidogrel in patients with AF and with at least 1 risk factor for stroke who receive ASA because they have a contraindication for oral anticoagulation or because they are unwilling to take an oral anticoagulant. ACTIVE I is a partial factorial, double-blind, placebo-controlled trial of irbesartan in patients participating in ACTIVE A or ACTIVE W. The primary outcomes of these studies are composites of vascular events. A total of 14000 patients will be enrolled in these trials. CONCLUSIONS: ACTIVE is the largest trial yet conducted in AF. Its results will lead to a new understanding of the role of combined antiplatelet therapy and the role of blood pressure lowering with an angiotensin II receptor blocker in patients with AF.
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| 31. |
- Dayton, K., et al.
(författare)
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Magmatic Storage and Volatile Fluxes of the 2021 La Palma Eruption
- 2024
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Ingår i: Geochemistry Geophysics Geosystems. - : American Geophysical Union (AGU). - 1525-2027. ; 25:6
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Tidskriftsartikel (refereegranskat)abstract
- The 2021 La Palma eruption (Tajogaite) was unprecedented in magnitude, duration, and degree of monitoring compared to historical volcanism on La Palma. Here, we provide data on melt inclusions in samples from the beginning and end of the eruption to compare the utility of both melt and fluid inclusions as recorders of magma storage. We also investigated compositional heterogeneities within the magmatic plumbing system. We found two populations of olivine crystals: a low Mg# (78–82) population present at the beginning and end of eruption, recording the maximum volatile contents (2.5 wt % H2O, 1,800 ppm F, 700 ppm Cl, 3,800 ppm S) and a higher Mg# (83–86) population sampled toward the end of the eruption, with lower volatile contents. Despite their host composition, melt inclusions share the same maximum range of CO2 concentrations (1.2–1.4 wt %), indicating olivine growth and inclusion capture at similar depths. Overall, both melt and fluid inclusions record similar pressures (450–850 MPa, ∼15–30 km), and when hosted in the same olivine crystal pressures are indistinguishable within error. At these mantle pressures, CO2 is expected to be an exsolved phase explaining the similar range of CO2 between the two samples, but other volatile species (F, Cl, S) behave incompatibly, and thus, the increase between the two olivine populations can be explained by fractional crystallization prior to eruption. Finally, based on our new data, we provide estimates on the total volatile emission of the eruption.
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| 32. |
- Deegan, Frances, et al.
(författare)
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Magma-Shale Interaction in Large Igneous Provinces : Implications for Climate Warming and Sulfide Genesis
- 2022
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Ingår i: Journal of Petrology. - : Oxford University Press. - 0022-3530 .- 1460-2415. ; 63:9
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Tidskriftsartikel (refereegranskat)abstract
- Large igneous provinces (LIPs) whose magma plumbing systems intersect sedimentary basins are linked to upheavals of Earths carbon and sulfur cycles and thus climate and life history. However, the underlying mechanistic links between these phenomena are elusive. We address this knowledge gap through short time-scale petrological experiments (1200 degrees C and 150 MPa) that explore interaction between basaltic melt and carbonaceous shale (mudstone) using starting materials from the Canadian High Arctic LIP and the Sverdrup Basin in which it intrudes. Here we show that entrainment of shale xenoliths in basaltic melt causes shale to shatter due to incipient thermal stress and devolatilization, which accelerates assimilation by increasing reactive surface area. Shale assimilation therefore facilitates transfer of sediment-derived volatile elements to LIP magma plumbing systems, whereupon carbon dominates the vapor phase while sulfur is partitioned into sulfide melt droplets. This study reveals that although carbon and sulfur are efficiently mobilized as a consequence of shale assimilation, sulfides can sequester sulfuran important climate cooling agentthus enhancing net emissions of climate warming greenhouse gases by shale-intersecting LIPs.
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| 33. |
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| 34. |
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| 35. |
- Dominguez-Valentin, M, et al.
(författare)
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No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database Study
- 2021
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 10:13
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Tidskriftsartikel (refereegranskat)abstract
- Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.
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| 36. |
- Dominguez-Valentin, M, et al.
(författare)
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Risk-Reducing Gynecological Surgery in Lynch Syndrome: Results of an International Survey from the Prospective Lynch Syndrome Database
- 2020
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To survey risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) practice and advice regarding hormone replacement therapy (HRT) in women with Lynch syndrome. Methods: We conducted a survey in 31 contributing centers from the Prospective Lynch Syndrome Database (PLSD), which incorporates 18 countries worldwide. The survey covered local policies for risk-reducing hysterectomy and BSO in Lynch syndrome, the timing when these measures are offered, the involvement of stakeholders and advice regarding HRT. Results: Risk-reducing hysterectomy and BSO are offered to path_MLH1 and path_MSH2 carriers in 20/21 (95%) contributing centers, to path_MSH6 carriers in 19/21 (91%) and to path_PMS2 carriers in 14/21 (67%). Regarding the involvement of stakeholders, there is global agreement (~90%) that risk-reducing surgery should be offered to women, and that this discussion may involve gynecologists, genetic counselors and/or medical geneticists. Prescription of estrogen-only HRT is offered by 15/21 (71%) centers to women of variable age range (35–55 years). Conclusions: Most centers offer risk-reducing gynecological surgery to carriers of path_MLH1, path_MSH2 and path_MSH6 variants but less so for path_PMS2 carriers. There is wide variation in how, when and to whom this is offered. The Manchester International Consensus Group developed recommendations to harmonize clinical practice across centers, but there is a clear need for more research.
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| 39. |
- Eriksson, L. S.E., et al.
(författare)
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Ultrasound-based risk model for preoperative prediction of lymph-node metastases in women with endometrial cancer : model-development study
- 2020
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Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 56:3, s. 443-452
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To develop a preoperative risk model, using endometrial biopsy results and clinical and ultrasound variables, to predict the individual risk of lymph-node metastases in women with endometrial cancer. Methods: A mixed-effects logistic regression model for prediction of lymph-node metastases was developed in 1501 prospectively included women with endometrial cancer undergoing transvaginal ultrasound examination before surgery, from 16 European centers. Missing data, including missing lymph-node status, were imputed. Discrimination, calibration and clinical utility of the model were evaluated using leave-center-out cross validation. The predictive performance of the model was compared with that of risk classification from endometrial biopsy alone (high-risk defined as endometrioid cancer Grade 3/non-endometrioid cancer) or combined endometrial biopsy and ultrasound (high-risk defined as endometrioid cancer Grade 3/non-endometrioid cancer/deep myometrial invasion/cervical stromal invasion/extrauterine spread). Results: Lymphadenectomy was performed in 691 women, of whom 127 had lymph-node metastases. The model for prediction of lymph-node metastases included the predictors age, duration of abnormal bleeding, endometrial biopsy result, tumor extension and tumor size according to ultrasound and undefined tumor with an unmeasurable endometrium. The model's area under the curve was 0.73 (95% CI, 0.68–0.78), the calibration slope was 1.06 (95% CI, 0.79–1.34) and the calibration intercept was 0.06 (95% CI, –0.15 to 0.27). Using a risk threshold for lymph-node metastases of 5% compared with 20%, the model had, respectively, a sensitivity of 98% vs 48% and specificity of 11% vs 80%. The model had higher sensitivity and specificity than did classification as high-risk, according to endometrial biopsy alone (50% vs 35% and 80% vs 77%, respectively) or combined endometrial biopsy and ultrasound (80% vs 75% and 53% vs 52%, respectively). The model's clinical utility was higher than that of endometrial biopsy alone or combined endometrial biopsy and ultrasound at any given risk threshold. Conclusions: Based on endometrial biopsy results and clinical and ultrasound characteristics, the individual risk of lymph-node metastases in women with endometrial cancer can be estimated reliably before surgery. The model is superior to risk classification by endometrial biopsy alone or in combination with ultrasound.
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| 45. |
- Hatos, Andras, et al.
(författare)
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DisProt : intrinsic protein disorder annotation in 2020
- 2020
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 48:D1, s. D269-D276
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Tidskriftsartikel (refereegranskat)abstract
- The Database of Protein Disorder (DisProt, URL:https://disprot.org) provides manually curated annotations of intrinsically disordered proteins from the literature. Here we report recent developments with DisProt (version 8), including the doubling of protein entries, a new disorder ontology, improvements of the annotation format and a completely new website. The website includes a redesigned graphical interface, a better search engine, a clearer API for programmatic access and a new annotation interface that integrates text mining technologies. The new entry format provides a greater flexibility, simplifies maintenance and allows the capture of more information from the literature. The new disorder ontology has been formalized and made interoperable by adopting the OWL format, as well as its structure and term definitions have been improved. The new annotation interface has made the curation process faster and more effective. We recently showed that new DisProt annotations can be effectively used to train and validate disorder predictors. We believe the growth of DisProt will accelerate, contributing to the improvement of function and disorder predictors and therefore to illuminate the 'dark' proteome.
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| 46. |
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| 47. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 48. |
- Kahanpää, Henrik, et al.
(författare)
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Convective vortices and dust devils at the MSL landing site : annual variability
- 2016
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Ingår i: Journal of Geophysical Research - Planets. - 2169-9097 .- 2169-9100. ; 121:8, s. 1514-1549
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Tidskriftsartikel (refereegranskat)abstract
- Two hundred fifty-two transient drops in atmospheric pressure, likely caused by passing convective vortices, were detected by the Rover Environmental Monitoring Station instrument during the first Martian year of the Mars Science Laboratory (MSL) landed mission. These events resembled the vortex signatures detected by the previous Mars landers Pathfinder and Phoenix; however, the MSL observations contained fewer pressure drops greater than 1.5 Pa and none greater than 3.0 Pa. Apparently, these vortices were generally not lifting dust as only one probable dust devil has been observed visually by MSL. The obvious explanation for this is the smaller number of strong vortices with large central pressure drops since according to Arvidson et al. [2014] ample dust seems to be present on the surface. The annual variation in the number of detected convective vortices followed approximately the variation in Dust Devil Activity (DDA) predicted by the MarsWRF numerical climate model. This result does not prove, however, that the amount of dust lifted by dust devils would depend linearly on DDA, as is assumed in several numerical models of the Martian atmosphere, since dust devils are only the most intense fraction of all convective vortices on Mars, and the amount of dust that can be lifted by a dust devil depends on its central pressure drop. Sol-to-sol variations in the number of vortices were usually small. However, on 1 Martian solar day a sudden increase in vortex activity, related to a dust storm front, was detected.
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