| 1. |
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- 2019
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Journal article (peer-reviewed)
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| 2. |
- Arndt, D. S., et al.
(author)
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State of the Climate in 2016
- 2017
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In: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
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Journal article (peer-reviewed)abstract
- In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
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| 3. |
- Arndt, D. S., et al.
(author)
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STATE OF THE CLIMATE IN 2017
- 2018
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In: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Research review (peer-reviewed)
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| 4. |
- Kattge, Jens, et al.
(author)
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TRY plant trait database - enhanced coverage and open access
- 2020
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In: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Journal article (peer-reviewed)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 5. |
- Leebens-Mack, James H., et al.
(author)
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One thousand plant transcriptomes and the phylogenomics of green plants
- 2019
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
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Journal article (peer-reviewed)abstract
- Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
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| 6. |
- Botvinik-Nezer, Rotem, et al.
(author)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Journal article (peer-reviewed)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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| 7. |
- Lundgren, Markus, et al.
(author)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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In: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Journal article (peer-reviewed)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 8. |
- Oliveros, Carl H., et al.
(author)
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Earth history and the passerine superradiation
- 2019
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:16, s. 7916-7925
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Journal article (peer-reviewed)abstract
- Avian diversification has been influenced by global climate change, plate tectonic movements, and mass extinction events. However, the impact of these factors on the diversification of the hyper-diverse perching birds (passerines) is unclear because family level relationships are unresolved and the timing of splitting events among lineages is uncertain. We analyzed DNA data from 4,060 nuclear loci and 137 passerine families using concatenation and coalescent approaches to infer a comprehensive phylogenetic hypothesis that clarifies relationships among all passerine families. Then, we calibrated this phylogeny using 13 fossils to examine the effects of different events in Earth history on the timing and rate of passerine diversification. Our analyses reconcile passerine diversification with the fossil and geological records; suggest that passerines originated on the Australian landmass ∼47 Ma; and show that subsequent dispersal and diversification of passerines was affected by a number of climatological and geological events, such as Oligocene glaciation and inundation of the New Zealand landmass. Although passerine diversification rates fluctuated throughout the Cenozoic, we find no link between the rate of passerine diversification and Cenozoic global temperature, and our analyses show that the increases in passerine diversification rate we observe are disconnected from the colonization of new continents. Taken together, these results suggest more complex mechanisms than temperature change or ecological opportunity have controlled macroscale patterns of passerine speciation.
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| 9. |
- Cerca, Jose, et al.
(author)
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The genomic basis of the plant island syndrome in Darwin's giant daisies
- 2022
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
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Journal article (peer-reviewed)abstract
- Many island plant species share a syndrome of characteristic phenotype and life history. Cerca et al. find the genomic basis of the plant island syndrome in one of Darwin's giant daisies, while separating ancestral genomes in a chromosome-resolved polyploid assembly. The repeated, rapid and often pronounced patterns of evolutionary divergence observed in insular plants, or the 'plant island syndrome', include changes in leaf phenotypes, growth, as well as the acquisition of a perennial lifestyle. Here, we sequence and describe the genome of the critically endangered, Galapagos-endemic species Scalesia atractyloides Arnot., obtaining a chromosome-resolved, 3.2-Gbp assembly containing 43,093 candidate gene models. Using a combination of fossil transposable elements, k-mer spectra analyses and orthologue assignment, we identify the two ancestral genomes, and date their divergence and the polyploidization event, concluding that the ancestor of all extant Scalesia species was an allotetraploid. There are a comparable number of genes and transposable elements across the two subgenomes, and while their synteny has been mostly conserved, we find multiple inversions that may have facilitated adaptation. We identify clear signatures of selection across genes associated with vascular development, growth, adaptation to salinity and flowering time, thus finding compelling evidence for a genomic basis of the island syndrome in one of Darwin's giant daisies.
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| 10. |
- Cox, Zachary L, et al.
(author)
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Guideline-Directed Medical Therapy Tolerability in Patients With Heart Failure and Mitral Regurgitation: The COAPT Trial.
- 2023
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In: JACC. Heart failure. - 2213-1787. ; 11:7, s. 791-805
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Journal article (peer-reviewed)abstract
- In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for HeartFailure Patients With Functional Mitral Regurgitation) trial, a central committee of heart failure (HF) specialists optimized guideline-directed medical therapies (GDMT) and documented medication and goal dose intolerances before patient enrollment.The authors sought to assess the rates, reasons, and predictors of GDMT intolerance in the COAPT trial.Baseline use, dose, and intolerances of angiotensin-converting enzyme inhibitors (ACEIs) angiotensin IIreceptor blockers (ARBs), angiotensin receptor neprilysin inhibitors (ARNIs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) were analyzed in patients with left ventricular ejection fraction (LVEF)≤40%, in whom maximally tolerated doses of these agents as assessed by an independent HF specialist were required before enrollment.A total of 464 patients had LVEF≤40% and complete medication information. At baseline, 38.8%, 39.4%, and 19.8% of patients tolerated 3, 2, and 1 GDMT classes, respectively (any dose); only 1.9% could not tolerate any GDMT. Beta-blockers were the most frequently tolerated GDMT (93.1%), followed by ACEIs/ARBs/ARNIs (68.5%), and then MRAs (55.0%). Intolerances differed by GDMT class, but hypotension and kidney dysfunction were most common. Goal doses were uncommonly achieved for beta-blockers (32.3%) and ACEIs/ARBs/ARNIs (10.2%) due to intolerances limiting titration. Only 2.2% of patients tolerated goal doses of all 3 GDMT classes.In a contemporary trial population with HF, severe mitral regurgitation, and systematic HF specialist-directed GDMT optimization, most patients had medical intolerances prohibiting 1 or more GDMT classes and achieving goal doses. The specific intolerances noted and methods used for GDMT optimization provide important lessons for the implementation of GDMT optimization in future clinical trials. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for HeartFailure Patients With Functional Mitral Regurgitation [The COAPT Trial] [COAPT]; NCT01626079).
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| 11. |
- Farooq, Vasim, et al.
(author)
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The CABG SYNTAX Score - an angiographic tool to grade the complexity of coronary disease following coronary artery bypass graft surgery : from the SYNTAX Left Main Angiographic (SYNTAX-LE MANS) substudy
- 2013
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In: EuroIntervention. - 1774-024X .- 1969-6213. ; 8:11, s. 1277-1285
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Journal article (peer-reviewed)abstract
- AIMS: The SYNTAX Score (SXscore) has established itself as an important prognostic tool in patients undergoing percutaneous coronary intervention (PCI). A limitation of the SXscore is the inability to differentiate outcomes in patients who have undergone prior coronary artery bypass graft (CABG) surgery. The CABG SXscore was devised to address this limitation.METHODS AND RESULTS: In the SYNTAX-LE MANS substudy 115 patients with unprotected left main coronary artery disease (isolated or associated with one, two or three-vessel disease) treated with CABG were prospectively assigned to undergo a 15-month coronary angiogram. An independent core laboratory analysed the baseline SXscore prior to CABG. The 15-month CABG SXscore was calculated by a panel of three interventional cardiologists. The CABG SXscore was calculated by determining the standard SXscore in the "native" coronary vessels ("native SXscore") and deducting points based on the importance of the diseased coronary artery segment (Leaman score) that have a functioning bypass graft anastomosed distally. Points relating to intrinsic coronary disease, such as bifurcation disease or calcification, remain unaltered. The mean 15-month CABG SXscore was significantly lower compared to the mean baseline SXscore (baseline SXscore 31.6, SD 13.1; 15-month CABG SXscore 21.2, SD 11.1; p<0.001). Reproducibility analyses (kappa [k] statistics) indicated a substantial agreement between CABG SXscore measurements (k=0.70; 95% CI [0.50-0.90], p<0.001), with the points deducted to calculate the CABG SXscore the most reproducible measurement (k=0.74; 95% CI [0.53-0.95], p<0.001). Despite the limited power of the study, four-year outcome data (Kaplan-Meier curves) demonstrated a trend towards reduced all-cause death (9.1% vs. 1.8%, p=0.084) and death/CVA/MI (16.4% vs. 7.0%, p=0.126) in the low compared to the high CABG SXscore group.CONCLUSIONS: In this pilot study the calculation of the CABG SXscore appeared feasible, reproducible and may have a long-term prognostic role in patients with complex coronary disease undergoing surgical revascularisation. Validation of this new scoring methodology is required.
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| 12. |
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| 13. |
- Field, Dawn, et al.
(author)
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The minimum information about a genome sequence (MIGS) specification.
- 2008
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In: Nature biotechnology. - : Springer Science and Business Media LLC. - 1546-1696 .- 1087-0156. ; 26:5, s. 541-7
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Journal article (peer-reviewed)abstract
- With the quantity of genomic data increasing at an exponential rate, it is imperative that these data be captured electronically, in a standard format. Standardization activities must proceed within the auspices of open-access and international working bodies. To tackle the issues surrounding the development of better descriptions of genomic investigations, we have formed the Genomic Standards Consortium (GSC). Here, we introduce the minimum information about a genome sequence (MIGS) specification with the intent of promoting participation in its development and discussing the resources that will be required to develop improved mechanisms of metadata capture and exchange. As part of its wider goals, the GSC also supports improving the 'transparency' of the information contained in existing genomic databases.
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| 14. |
- Kosmidou, Ioanna, et al.
(author)
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Sex-Specific Outcomes of Transcatheter Mitral-Valve Repair and Medical Therapy for Mitral Regurgitation in Heart Failure.
- 2021
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In: JACC. Heart failure. - 2213-1787.
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Journal article (peer-reviewed)abstract
- This study sought to assess the sex-specific outcomes in patients with heart failure (HF) with 3+ and 4+ secondary mitral regurgitation (SMR) treated with transcatheter mitral valve repair (TMVr) plus guideline-directed medical therapy (GDMT) versus GDMT alone in the COAPT trial.The impact of sex in patients with HF and severe SMR treated with TMVr with the MitraClip compared with GDMT alone is unknown.Patients were randomized 1:1 to TMVr versus GDMT alone. Two-year outcomes were examined according to sex.Among 614 patients, 221 (36.0%) were women. Women were younger than men and had fewer comorbidities, but reduced quality of life and functional capacity at baseline. In a joint frailty model accounting for the competing risk of death, the 2-year cumulative incidence of the primary endpoint of all HF hospitalizations (HFH) was higher in men compared with women treated with GDMT alone. However, the relative reduction in HFHs with TMVr was greater in men (HR: 0.43; 95% CI: 0.34-0.54) than women (HR: 0.78; 95% CI: 0.57-1.05) (Pinteraction = 0.002). A significant interaction between TMVr versus GDMT alone treatment and time was present for all HFHs in women (HR: 0.57; 95% CI: 0.39-0.84, and HR: 1.39; 95% CI: 0.83-2.33 between 0-1 year and 1-2 years after randomization, respectively, Pinteraction = 0.007) but not in men (HR: 0.48; 95% CI: 0.36-0.64, and HR: 0.33; 95% CI: 0.21-0.51; Pinteraction = 0.16). Female sex was independently associated with a lower adjusted risk of death at 2 years (HR: 0.64; 95% CI: 0.46-0.90; P = 0.011). TMVr consistently reduced 2-year mortality compared with GDMT alone, irrespective of sex (Pinteraction = 0.99).In the COAPT trial, TMVr with the MitraClip resulted in improved clinical outcomes compared with GDMT alone, irrespective of sex. However, the impact of TMVr in reducing HFH was less pronounced in women compared with men beyond the first year after treatment. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Tria] [COAPT]) NCT01626079.
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| 15. |
- Ludwig, Sebastian, et al.
(author)
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Transcatheter Mitral Valve Replacement versus Medical Therapy for Secondary Mitral Regurgitation: A Propensity Score-Matched Comparison.
- 2023
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In: Circulation. Cardiovascular interventions. - 1941-7632. ; 16:6
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Journal article (peer-reviewed)abstract
- Background: Transcatheter mitral valve replacement (TMVR) is an emerging therapeutic alternative for patients with secondary mitral regurgitation (MR). Outcomes of TMVR versus guideline-directed medical therapy (GDMT) have not been investigated for this population. This study aimed to compare clinical outcomes of patients with secondary MR undergoing TMVR versus GDMT alone. Methods: The CHOICE-MI registry included patients with MR undergoing TMVR using dedicated devices. Patients with MR etiologies other than secondary MR were excluded. Patients treated with GDMT alone were derived from the control arm of the COAPT trial. We compared outcomes between the TMVR and GDMT groups, using propensity score (PS)-matching to adjust for baseline differences. Results: After PS-matching, 97 patient pairs undergoing TMVR (72.9±8.7 years, 60.8% male, transapical access 91.8%) versus GDMT (73.1±11.0 years, 59.8% male) were compared. At 1 and 2 years, residual MR was ≤1+ in all patients of the TMVR group compared to 6.9% and 7.7%, respectively, in those receiving GDMT alone (both p<0.001). The 2-year rate of HF hospitalization was significantly lower in the TMVR group (32.8% vs. 54.4%, HR 0.59, 95% CI 0.35-0.99; p=0.04). Among survivors, a higher proportion of patients were in NYHA functional class I or II in the TMVR group at 1 year (78.2% vs. 59.7%, p=0.03) and at 2 years (77.8% vs. 53.2%, p=0.09). Two-year mortality was similar in the two groups (TMVR vs. GDMT, 36.8% vs. 40.8%, HR 1.01, 95% CI 0.62-1.64; p=0.98). Conclusions: In this observational comparison, over 2-year follow-up, TMVR using mostly transapical devices in patients with secondary MR was associated with significant reduction of MR, symptomatic improvement, less frequent hospitalizations for HF and similar mortality compared with GDMT.
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| 16. |
- Sawcer, Stephen, et al.
(author)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Journal article (peer-reviewed)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 17. |
- Vlasschaert, Caitlyn, et al.
(author)
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A practical approach to curate clonal hematopoiesis of indeterminate potential in human genetic data sets
- 2023
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 141:18, s. 2214-2223
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Journal article (peer-reviewed)abstract
- Clonal hematopoiesis of indeterminate potential (CHIP) is a common form of age-related somatic mosaicism that is associated with significant morbidity and mortality. CHIP mutations can be identified in peripheral blood samples that are sequenced using approaches that cover the whole genome, the whole exome, or targeted genetic regions; however, differentiating true CHIP mutations from sequencing artifacts and germ line variants is a considerable bioinformatic challenge. We present a stepwise method that combines filtering based on sequencing metrics, variant annotation, and population-based associations to increase the accuracy of CHIP calls. We apply this approach to ascertain CHIP in ∼550 000 individuals in the UK Biobank complete whole exome cohort and the All of Us Research Program initial whole genome release cohort. CHIP ascertainment on this scale unmasks recurrent artifactual variants and highlights the importance of specialized filtering approaches for several genes, including TET2 and ASXL1. We show how small changes in filtering parameters can considerably increase CHIP misclassification and reduce the effect size of epidemiological associations. Our high-fidelity call set refines previous population-based associations of CHIP with incident outcomes. For example, the annualized incidence of myeloid malignancy in individuals with small CHIP clones is 0.03% per year, which increases to 0.5% per year among individuals with very large CHIP clones. We also find a significantly lower prevalence of CHIP in individuals of self-reported Latino or Hispanic ethnicity in All of Us, highlighting the importance of including diverse populations. The standardization of CHIP calling will increase the fidelity of CHIP epidemiological work and is required for clinical CHIP diagnostic assays.
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| 18. |
- Weinstock, Joshua S, et al.
(author)
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Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis.
- 2023
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In: Nature. - 1476-4687. ; 616:7958, s. 755-763
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Journal article (peer-reviewed)abstract
- Mutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis1. These lesions are precursors for blood cancers2-6, but the basis of their fitness advantage remains largely unknown, partly owing to a paucity of large cohorts in which the clonal expansion rate has been assessed by longitudinal sampling. Here, to circumvent this limitation, we developed a method to infer the expansion rate from data from a single time point. We applied this method to 5,071 people with clonal haematopoiesis. A genome-wide association study revealed that a common inherited polymorphism in the TCL1A promoter was associated with a slower expansion rate in clonal haematopoiesis overall, but the effect varied by driver gene. Those carrying this protective allele exhibited markedly reduced growth rates or prevalence of clones with driver mutations in TET2, ASXL1, SF3B1 and SRSF2, butthis effect was not seen inclones withdriver mutations in DNMT3A. TCL1A was not expressed in normal or DNMT3A-mutated HSCs, but the introduction of mutations in TET2 or ASXL1 led to the expression of TCL1A protein and the expansion of HSCs in vitro. The protective allele restricted TCL1A expression and expansion of mutant HSCs, as did experimentalknockdown of TCL1A expression. Forced expression of TCL1A promoted the expansion of human HSCs in vitro and mouse HSCs in vivo. Our results indicate that the fitness advantage of several commonly mutated driver genes in clonal haematopoiesis may be mediated by TCL1A activation.
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| 19. |
- Abbott, Benjamin W., et al.
(author)
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Biomass offsets little or none of permafrost carbon release from soils, streams, and wildfire : an expert assessment
- 2016
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In: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 11:3
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Journal article (peer-reviewed)abstract
- As the permafrost region warms, its large organic carbon pool will be increasingly vulnerable to decomposition, combustion, and hydrologic export. Models predict that some portion of this release will be offset by increased production of Arctic and boreal biomass; however, the lack of robust estimates of net carbon balance increases the risk of further overshooting international emissions targets. Precise empirical or model-based assessments of the critical factors driving carbon balance are unlikely in the near future, so to address this gap, we present estimates from 98 permafrost-region experts of the response of biomass, wildfire, and hydrologic carbon flux to climate change. Results suggest that contrary to model projections, total permafrost-region biomass could decrease due to water stress and disturbance, factors that are not adequately incorporated in current models. Assessments indicate that end-of-the-century organic carbon release from Arctic rivers and collapsing coastlines could increase by 75% while carbon loss via burning could increase four-fold. Experts identified water balance, shifts in vegetation community, and permafrost degradation as the key sources of uncertainty in predicting future system response. In combination with previous findings, results suggest the permafrost region will become a carbon source to the atmosphere by 2100 regardless of warming scenario but that 65%-85% of permafrost carbon release can still be avoided if human emissions are actively reduced.
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| 20. |
- Alfredsson, Joakim, et al.
(author)
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Gait Speed Predicts 30-Day Mortality After Transcatheter Aortic Valve Replacement Results From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry
- 2016
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In: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 133:14, s. 1351-1359
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Journal article (peer-reviewed)abstract
- Background Surgical risk scores do not include frailty assessments (eg, gait speed), which are of particular importance for patients with severe aortic stenosis considering transcatheter aortic valve replacement. Methods and Results We assessed the association of 5-m gait speed with outcomes in a cohort of 8039 patients who underwent transcatheter aortic valve replacement (November 2011-June 2014) and were included in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. We evaluated the association between continuous and categorical gait speed and 30-day all-cause mortality before and after adjustment for Society of Thoracic Surgeons-predicted risk of mortality score and key variables. Secondary outcomes included in-hospital mortality, bleeding, acute kidney injury, and stroke. The overall median gait speed was 0.63 m/s (25th-75th percentile, 0.47-0.79 m/s), with the slowest walkers (<0.5 m/s) constituting 28%, slow walkers (0.5-0.83 m/s) making up 48%, and normal walkers (>0.83 m/s) constituting 24% of the population. Thirty-day all-cause mortality rates were 8.4%, 6.6%, and 5.4% for the slowest, slow, and normal walkers, respectively (P<0.001). Each 0.2-m/s decrease in gait speed corresponded to an 11% increase in 30-day mortality (adjusted odds ratio, 1.11; 95% confidence interval, 1.01-1.22). The slowest walkers had 35% higher 30-day mortality than normal walkers (adjusted odds ratio, 1.35; 95% confidence interval, 1.01-1.80), significantly longer hospital stays, and a lower probability of being discharged to home. Conclusions Gait speed is independently associated with 30-day mortality after transcatheter aortic valve replacement. Identification of frail patients with the slowest gait speeds facilitates preprocedural evaluation and anticipation of a higher level of postprocedural care. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01737528.
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| 21. |
- Balthasar, Michael, et al.
(author)
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Implementation and validation of a new soot model and application to aeroengine combustors
- 2002
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In: Journal of Engineering for Gas Turbines and Power. - : ASME International. - 1528-8919 .- 0742-4795. ; 124:1, s. 66-74
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Journal article (peer-reviewed)abstract
- The modeling of soot formation and oxidation under industrially relevant conditions has made significant progress in recent years. Simplified models introducing a small number of transport equations into a CFD Code have been used with some success in research configurations simulating a reciprocating diesel engine. Soot formation and oxidation in the turbulent flow is calculated on the basis of a laminar flamelet library model. The gas phase reactions are modeled with a detailed mechanism for the combustion of heptane containing 89 species and 855 reactions developed by Frenklach and Warnatz and revised by Mauss. The soot model is divided into gas phase reactions. the growth of polycyclic aromatic hydrocarbons (PAH) and the processes of particle inception, heterogeneous face growth, oxidation, and condensation. The first two are modeled within the laminar flamelet chemistry, while the soot model deals with the soot particle processes. The time scales of soot formation are assumed to he much larger than the turbulent time scales. Therefore rates of soot formation are tabulated in the flamelet libraries rather than the soot volume fraction itself. The different rates of soot formation, e.g., particle inception, sinface growth, firagmentation, and oxidation, computed on the basis of a detailed soot model, are calculated in the dissipation rate space and further simplified by fitting them to simple analytical functions. A transport equation for the mean soot mass fraction is solved in the CFD code. The mean rate in this transport equation is closed with the help of presumed probability density functions for the mixture fraction and the scalar dissipation rate. Heat loss due to radiation can be taken into account by including a heat loss parameter it? the flamelet calculations describing the change of enthalpy due to radiation, but was not used for the results reported here. The soot model was integrated into an existing commercial CFD code is a post-processing module to existing combustion CFD flow fields and is very robust with high convergence rates. The model is validated with laboratory flame data and using a realistic three-dimensional BM V Rolls-Royce combustor configuration, where test data at high pressure are available. Good agreement between experiment and simulation is achieved for laboratory flames, whereas soot is overpredicted for the aeroengine combustor configuration by 1-2 orders of magnitude.
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| 22. |
- Berner, Logan T., et al.
(author)
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The Arctic plant aboveground biomass synthesis dataset
- 2024
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In: Scientific Data. - : Springer Nature. - 2052-4463. ; 11:1
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Journal article (peer-reviewed)abstract
- Plant biomass is a fundamental ecosystem attribute that is sensitive to rapid climatic changes occurring in the Arctic. Nevertheless, measuring plant biomass in the Arctic is logistically challenging and resource intensive. Lack of accessible field data hinders efforts to understand the amount, composition, distribution, and changes in plant biomass in these northern ecosystems. Here, we present The Arctic plant aboveground biomass synthesis dataset, which includes field measurements of lichen, bryophyte, herb, shrub, and/or tree aboveground biomass (g m−2) on 2,327 sample plots from 636 field sites in seven countries. We created the synthesis dataset by assembling and harmonizing 32 individual datasets. Aboveground biomass was primarily quantified by harvesting sample plots during mid- to late-summer, though tree and often tall shrub biomass were quantified using surveys and allometric models. Each biomass measurement is associated with metadata including sample date, location, method, data source, and other information. This unique dataset can be leveraged to monitor, map, and model plant biomass across the rapidly warming Arctic.
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| 23. |
- Bourantas, Christos V., et al.
(author)
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Prognostic Implications of Severe Coronary Calcification in Patients Undergoing Coronary Artery Bypass Surgery : An Analysis of the SYNTAX Study
- 2015
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In: Catheterization and cardiovascular interventions. - : Wiley. - 1522-1946 .- 1522-726X. ; 85:2, s. 199-206
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Journal article (peer-reviewed)abstract
- ObjectivesTo investigate the prognostic implications of the presence of severe lesion calcification in patients undergoing coronary artery bypass graft (CABG) operation. BackgroundThere is robust evidence that lesion calcification is a predictor of worse prognosis in patients undergoing percutaneous coronary intervention; however, there is limited data about the prognostic implication of lesion calcium in patients treated with CABG. MethodsWe retrospectively analyzed data from 1,545 patients who underwent CABG and were recruited in the SYNTAX study and CABG registry. Two experts reviewed the angiographic data and classified patients in two groups: those with severely calcified coronary arteries and those without severe lesion calcification. Clinical outcomes at 5-year follow-up were collected and compared in the two groups. ResultsOne out of three patients exhibited severe lesion calcification (n=588). Patients with calcified coronaries had an increased mortality at 5-year follow-up (17.1% vs. 9.9%, P<0.001) and a higher event rate of death-myocardial infarction (MI) compared with those without (19.4% vs. 13.2%, P=0.003), but there was no statistical significant difference between the two groups for major adverse cardiovascular events (MACE, 26.8% vs. 21.8%, P=0.057). In multivariate Cox regression analysis severe lesion calcification was an independent predictor of an increased all-cause mortality (hazard ratio: 1.39, 95% confidence interval: 1.02-1.89; P=0.037) but it was not an independent predictor of the combined end-points death-MI or MACE. ConclusionsSevere lesion calcification is associated with an increased mortality in patients undergoing CABG, but it is not an independent predictor of death-MI or MACE. This paradox can be attributed to the fact that CABG allows perfusion of the healthy coronaries bypassing the diseased arteries and thus it minimizes the risk of coronary events due to progressive atherosclerosis. (c) 2014 Wiley Periodicals, Inc.
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| 24. |
- Brack, Werner, et al.
(author)
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The SOLUTIONS project : Challenges and responses for present and future emerging pollutants in land and water resources management
- 2015
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In: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 503, s. 22-31
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Journal article (peer-reviewed)abstract
- SOLUTIONS (2013 to 2018) is a European Union Seventh Framework Programme Project (EU-FP7). The project aims to deliver a conceptual framework to support the evidence-based development of environmental policies with regard to water quality. SOLUTIONS will develop the tools for the identification, prioritisation and assessment of those water contaminants that may pose a risk to ecosystems and human health. To this end, a new generation of chemical and effect-based monitoring tools is developed and integrated with a full set of exposure, effect and risk assessment models. SOLUTIONS attempts to address legacy, present and future contamination by integrating monitoring and modelling based approaches with scenarios on future developments in society, economy and technology and thus in contamination. The project follows a solutions-oriented approach by addressing major problems of water and chemicals management and by assessing abatement options. SOLUTIONS takes advantage of the access to the infrastructure necessary to investigate the large basins of the Danube and Rhine as well as relevant Mediterranean basins as case studies, and puts major efforts on stakeholder dialogue and support. Particularly, the EU Water Framework Directive (WFD) Common Implementation Strategy (CIS) working groups, International River Commissions, and water works associations are directly supported. with consistent guidance for the early detection, identification, prioritisation, and abatement of chemicals in the water cycle. SOLUTIONS will give a specific emphasis on concepts and tools for the impact and risk assessment of complex mixtures of emerging pollutants, their metabolites and transformation products. Analytical and effect-based screening tools will be applied together with ecological assessment tools for the identification of toxicants and their impacts. The SOLUTIONS approach is expected to provide transparent and evidence-based candidates or River Basin Specific Pollutants in the case study basins and to assist future review of priority pollutants under the WFD as well as potential abatement options.
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| 25. |
- Coisne, Augustin, et al.
(author)
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Regurgitant Volume to LA Volume Ratio in Patients with Secondary MR: The COAPT Trial.
- 2024
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In: European Heart Journal-Cardiovascular Imaging. - 2047-2404 .- 2047-2412. ; 25:5, s. 616-625
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Journal article (peer-reviewed)abstract
- The conceptual framework of proportionate versus disproportionate mitral regurgitation (MR) translates poorly to individual patients with heart failure (HF) and secondary MR. A novel index, the ratio of MR severity to left atrial volume (LAV), may identify patients with "disproportionate" MR and a higher risk of events. The objectives, therefore, were to investigate the prognostic impact of MR severity to LAV ratio on outcomes among HF patients with severe secondary MR randomized to transcatheter edge-to-edge repair (TEER) with the MitraClipTM device plus guideline-directed medical therapy (GDMT) vs. GDMT alone in the COAPT trial.The ratio of preprocedural regurgitant volume (RVol) to LAV was calculated from baseline transthoracic echocardiograms. The primary endpoint was 2-year covariate-adjusted rate of HF hospitalization (HFH).Among 567 patients, the median RVol/LAV was 0.67 (IQR 0.48-0.91). In patients randomized to GDMT alone, lower RVol/LAV was independently associated with an increased 2-year risk of HFH (adjHR: 1.77; 95% CI: 1.20-2.63). RVol/LAV was a stronger predictor of adverse outcomes than RVol or LAV alone. Treatment with TEER plus GDMT compared with GDMT alone was associated with lower 2-year rates of HFH both in patients with low and high RVol/LAV (Pinteraction=0.28). Baseline RVol/LAV ratio was unrelated to 2-year mortality, health status, or functional capacity in either treatment group.Low RVol/LAV ratio was an independent predictor of 2-year HFH in HF patients with severe MR treated with GDMT alone in the COAPT trial. TEER improved outcomes regardless of baseline RVol/LAV ratio.Trial Name: Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (The COAPT Trial) (COAPT) ClinicalTrial.gov Identifier: NCT01626079 URL: https://clinicaltrials.gov/ct2/show/NCT01626079.
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