| 1. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Arndt, D. S., et al.
(författare)
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STATE OF THE CLIMATE IN 2017
- 2018
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Forskningsöversikt (refereegranskat)
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| 9. |
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| 10. |
- Arndt, D. S., et al.
(författare)
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State of the Climate in 2016
- 2017
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
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Tidskriftsartikel (refereegranskat)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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| 11. |
- Dunn, R. J. H., et al.
(författare)
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GLOBAL CLIMATE : State of the Climate in 2020
- 2021
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Ingår i: Bulletin of the American Meteorological Society. - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 102:8
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Tidskriftsartikel (refereegranskat)
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| 12. |
- Nolte, I. M., et al.
(författare)
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Genetic loci associated with heart rate variability and their effects on cardiac disease risk
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74 < r(g) < -0.55) and blood pressure (-0.35 < r(g) < -0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.
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| 13. |
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| 14. |
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| 15. |
- Erni, W., et al.
(författare)
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Technical design report for the PANDA (AntiProton Annihilations at Darmstadt) Straw Tube Tracker
- 2013
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Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 49:2
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Tidskriftsartikel (refereegranskat)abstract
- This document describes the technical layout and the expected performance of the Straw Tube Tracker (STT), the main tracking detector of the PANDA target spectrometer. The STT encloses a Micro-Vertex-Detector (MVD) for the inner tracking and is followed in beam direction by a set of GEM stations. The tasks of the STT are the measurement of the particle momentum from the reconstructed trajectory and the measurement of the specific energy loss for a particle identification. Dedicated simulations with full analysis studies of certain proton-antiproton reactions, identified as being benchmark tests for the whole PANDA scientific program, have been performed to test the STT layout and performance. The results are presented, and the time lines to construct the STT are described.
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| 16. |
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Lango Allen, Hana, et al.
(författare)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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| 23. |
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| 24. |
- Ades, M., et al.
(författare)
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Global Climate : in State of the climate in 2019
- 2020
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 101:8, s. S17-S127
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Tidskriftsartikel (refereegranskat)
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| 25. |
- Ades, M., et al.
(författare)
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GLOBAL CLIMATE
- 2020
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Ingår i: BULLETIN OF THE AMERICAN METEOROLOGICAL SOCIETY. - 0003-0007 .- 1520-0477. ; 101:8
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Tidskriftsartikel (refereegranskat)
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| 26. |
- Kulmala, M., et al.
(författare)
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General overview: European Integrated project on Aerosol Cloud Climate and Air Quality interactions (EUCAARI) - integrating aerosol research from nano to global scales
- 2011
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 11:24, s. 13061-13143
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we describe and summarize the main achievements of the European Aerosol Cloud Climate and Air Quality Interactions project (EUCAARI). EUCAARI started on 1 January 2007 and ended on 31 December 2010 leaving a rich legacy including: (a) a comprehensive database with a year of observations of the physical, chemical and optical properties of aerosol particles over Europe, (b) comprehensive aerosol measurements in four developing countries, (c) a database of airborne measurements of aerosols and clouds over Europe during May 2008, (d) comprehensive modeling tools to study aerosol processes fron nano to global scale and their effects on climate and air quality. In addition a new Pan-European aerosol emissions inventory was developed and evaluated, a new cluster spectrometer was built and tested in the field and several new aerosol parameterizations and computations modules for chemical transport and global climate models were developed and evaluated. These achievements and related studies have substantially improved our understanding and reduced the uncertainties of aerosol radiative forcing and air quality-climate interactions. The EUCAARI results can be utilized in European and global environmental policy to assess the aerosol impacts and the corresponding abatement strategies.
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| 27. |
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| 28. |
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| 29. |
- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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| 30. |
- Momozawa, Y, et al.
(författare)
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IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2427-
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Tidskriftsartikel (refereegranskat)abstract
- GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach.
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| 31. |
- Aaron-Morrison, Arlene P., et al.
(författare)
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State of the climate in 2014
- 2015
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Ingår i: Bulletin of the American Meteorological Society. - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 96
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Tidskriftsartikel (refereegranskat)abstract
- Most of the dozens of essential climate variables monitored each year in this report continued to follow their long-term trends in 2014, with several setting new records. Carbon dioxide, methane, and nitrous oxide-the major greenhouse gases released into Earth's atmosphere-once again all reached record high average atmospheric concentrations for the year. Carbon dioxide increased by 1.9 ppm to reach a globally averaged value of 397.2 ppm for 2014. Altogether, 5 major and 15 minor greenhouse gases contributed 2.94 W m-2 of direct radiative forcing, which is 36% greater than their contributions just a quarter century ago. Accompanying the record-high greenhouse gas concentrations was nominally the highest annual global surface temperature in at least 135 years of modern record keeping, according to four independent observational analyses. The warmth was distributed widely around the globe's land areas, Europe observed its warmest year on record by a large margin, with close to two dozen countries breaking their previous national temperature records; many countries in Asia had annual temperatures among their 10 warmest on record; Africa reported above-average temperatures across most of the continent throughout 2014; Australia saw its third warmest year on record, following record heat there in 2013; Mexico had its warmest year on record; and Argentina and Uruguay each had their second warmest year on record. Eastern North America was the only major region to observe a below-average annual temperature. But it was the oceans that drove the record global surface temperature in 2014. Although 2014 was largely ENSO-neutral, the globally averaged sea surface temperature (SST) was the highest on record. The warmth was particularly notable in the North Pacific Ocean where SST anomalies signaled a transition from a negative to positive phase of the Pacific decadal oscillation. In the winter of 2013/14, unusually warm water in the northeast Pacific was associated with elevated ocean heat content anomalies and elevated sea level in the region. Globally, upper ocean heat content was record high for the year, reflecting the continued increase of thermal energy in the oceans, which absorb over 90% of Earth's excess heat from greenhouse gas forcing. Owing to both ocean warming and land ice melt contributions, global mean sea level in 2014 was also record high and 67 mm greater than the 1993 annual mean, when satellite altimetry measurements began. Sea surface salinity trends over the past decade indicate that salty regions grew saltier while fresh regions became fresher, suggestive of an increased hydrological cycle over the ocean expected with global warming. As in previous years, these patterns are reflected in 2014 subsurface salinity anomalies as well. With a now decade-long trans-basin instrument array along 26°N, the Atlantic meridional overturning circulation shows a decrease in transport of-4.2 ± 2.5 Sv decade-1. Precipitation was quite variable across the globe. On balance, precipitation over the world's oceans was above average, while below average across land surfaces. Drought continued in southeastern Brazil and the western United States. Heavy rain during April-June led to devastating floods in Canada's Eastern Prairies. Above-normal summer monsoon rainfall was observed over the southern coast of West Africa, while drier conditions prevailed over the eastern Sahel. Generally, summer monsoon rainfall over eastern Africa was above normal, except in parts of western South Sudan and Ethiopia. The south Asian summer monsoon in India was below normal, with June record dry. Across the major tropical cyclone basins, 91 named storms were observed during 2014, above the 1981-2010 global average of 82. The Eastern/Central Pacific and South Indian Ocean basins experienced significantly above-normal activity in 2014; all other basins were either at or below normal. The 22 named storms in the Eastern/Central Pacific was the basin's most since 1992. Similar to 2013, the North Atlantic season was quieter than most years of the last two decades with respect to the number of storms, despite the absence of El Niño conditions during both years. In higher latitudes and at higher elevations, increased warming continued to be visible in the decline of glacier mass balance, increasing permafrost temperatures, and a deeper thawing layer in seasonally frozen soil. In the Arctic, the 2014 temperature over land areas was the fourth highest in the 115-year period of record and snow melt occurred 20-30 days earlier than the 1998-2010 average. The Greenland Ice Sheet experienced extensive melting in summer 2014. The extent of melting was above the 1981-2010 average for 90% of the melt season, contributing to the second lowest average summer albedo over Greenland since observations began in 2000 and a record-low albedo across the ice sheet for August. On the North Slope of Alaska, new record high temperatures at 20-m depth were measured at four of five permafrost observatories. In September, Arctic minimum sea ice extent was the sixth lowest since satellite records began in 1979. The eight lowest sea ice extents during this period have occurred in the last eight years. Conversely, in the Antarctic, sea ice extent countered its declining trend and set several new records in 2014, including record high monthly mean sea ice extent each month from April to November. On 20 September, a record large daily Antarctic sea ice extent of 20.14 × 106 km2 occurred. The 2014 Antarctic stratospheric ozone hole was 20.9 million km2 when averaged from 7 September to 13 October, the sixth smallest on record and continuing a decrease, albeit statistically insignificant, in area since 1998.
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| 32. |
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| 33. |
- Ebersole, Charles R., et al.
(författare)
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Many Labs 5: Testing Pre-Data-Collection Peer Review as an Intervention to Increase Replicability
- 2020
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Ingår i: Advances in Methods and Practices in Psychological Science. - : Sage. - 2515-2467 .- 2515-2459. ; 3:3, s. 309-331
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Tidskriftsartikel (refereegranskat)abstract
- Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3-9; median total sample = 1,279.5, range = 276-3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (Delta r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00-.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19-.50).
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| 34. |
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| 35. |
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| 36. |
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| 37. |
- Bellouin, N., et al.
(författare)
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Bounding Global Aerosol Radiative Forcing of Climate Change
- 2020
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Ingår i: Reviews of geophysics. - 8755-1209 .- 1944-9208. ; 58:1
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Forskningsöversikt (refereegranskat)abstract
- Aerosols interact with radiation and clouds. Substantial progress made over the past 40 years in observing, understanding, and modeling these processes helped quantify the imbalance in the Earth's radiation budget caused by anthropogenic aerosols, called aerosol radiative forcing, but uncertainties remain large. This review provides a new range of aerosol radiative forcing over the industrial era based on multiple, traceable, and arguable lines of evidence, including modeling approaches, theoretical considerations, and observations. Improved understanding of aerosol absorption and the causes of trends in surface radiative fluxes constrain the forcing from aerosol-radiation interactions. A robust theoretical foundation and convincing evidence constrain the forcing caused by aerosol-driven increases in liquid cloud droplet number concentration. However, the influence of anthropogenic aerosols on cloud liquid water content and cloud fraction is less clear, and the influence on mixed-phase and ice clouds remains poorly constrained. Observed changes in surface temperature and radiative fluxes provide additional constraints. These multiple lines of evidence lead to a 68% confidence interval for the total aerosol effective radiative forcing of -1.6 to -0.6Wm(-2), or -2.0 to -0.4Wm(-2) with a 90% likelihood. Those intervals are of similar width to the last Intergovernmental Panel on Climate Change assessment but shifted toward more negative values. The uncertainty will narrow in the future by continuing to critically combine multiple lines of evidence, especially those addressing industrial-era changes in aerosol sources and aerosol effects on liquid cloud amount and on ice clouds. Plain Language Summary Human activities emit into the atmosphere small liquid and solid particles called aerosols. Those aerosols change the energy budget of the Earth and trigger climate changes, by scattering and absorbing solar and terrestrial radiation and playing important roles in the formation of cloud droplets and ice crystals. But because aerosols are much more varied in their chemical composition and much more heterogeneous in their spatial and temporal distributions than greenhouse gases, their perturbation to the energy budget, called radiative forcing, is much more uncertain. This review uses traceable and arguable lines of evidence, supported by aerosol studies published over the past 40 years, to quantify that uncertainty. It finds that there are two chances out of three that aerosols from human activities have increased scattering and absorption of solar radiation by 14% to 29% and cloud droplet number concentration by 5 to 17% in the period 2005-2015 compared to the year 1850. Those increases exert a radiative forcing that offsets between a fifth and a half of the radiative forcing by greenhouse gases. The degree to which human activities affect natural aerosol levels, and the response of clouds, and especially ice clouds, to aerosol perturbations remain particularly uncertain.
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| 38. |
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| 39. |
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| 40. |
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| 41. |
- Buntgen, U., et al.
(författare)
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Recognising bias in Common Era temperature reconstructions
- 2022
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Ingår i: Dendrochronologia. - : Elsevier BV. - 1125-7865 .- 1612-0051. ; 74
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Tidskriftsartikel (refereegranskat)abstract
- A steep decline in the quality and quantity of available climate proxy records before medieval times challenges any comparison of reconstructed temperature and hydroclimate trends and extremes between the first and second half of the Common Era. Understanding of the physical causes, ecological responses and societal consequences of past climatic changes, however, demands highly-resolved, spatially-explicit, seasonally-defined and absolutely-dated archives over the entire period in question. Continuous efforts to improve existing proxy records and reconstruction methods and to develop new ones, as well as clear communication of all uncertainties (within and beyond academia) must be central tasks for the paleoclimate community.
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| 42. |
- Büntgen, Ulf, et al.
(författare)
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The influence of decision-making in tree ring-based climate reconstructions
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Tree-ring chronologies underpin the majority of annually-resolved reconstructions of Common Era climate. However, they are derived using different datasets and techniques, the ramifications of which have hitherto been little explored. Here, we report the results of a double-blind experiment that yielded 15 Northern Hemisphere summer temperature reconstructions from a common network of regional tree-ring width datasets. Taken together as an ensemble, the Common Era reconstruction mean correlates with instrumental temperatures from 1794–2016 CE at 0.79 (p < 0.001), reveals summer cooling in the years following large volcanic eruptions, and exhibits strong warming since the 1980s. Differing in their mean, variance, amplitude, sensitivity, and persistence, the ensemble members demonstrate the influence of subjectivity in the reconstruction process. We therefore recommend the routine use of ensemble reconstruction approaches to provide a moreconsensual picture of past climate variability.
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| 43. |
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| 44. |
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| 45. |
- Muncke, Jane, et al.
(författare)
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A vision for safer food contact materials: Public health concerns as drivers for improved testing
- 2023
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Ingår i: ENVIRONMENT INTERNATIONAL. - 0160-4120 .- 1873-6750. ; 180
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Tidskriftsartikel (refereegranskat)abstract
- Food contact materials (FCMs) and food contact articles are ubiquitous in today's globalized food system. Chemicals migrate from FCMs into foodstuffs, so called food contact chemicals (FCCs), but current regulatory requirements do not sufficiently protect public health from hazardous FCCs because only individual substances used to make FCMs are tested and mostly only for genotoxicity while endocrine disruption and other hazard properties are disregarded. Indeed, FCMs are a known source of a wide range of hazardous chemicals, and they likely contribute to highly prevalent non-communicable diseases. FCMs can also include non-intentionally added substances (NIAS), which often are unknown and therefore not subject to risk assessment. To address these important shortcomings, we outline how the safety of FCMs may be improved by (1) testing the overall migrate, including (unknown) NIAS, of finished food contact articles, and (2) expanding toxicological testing beyond genotoxicity to multiple endpoints associated with non-communicable diseases relevant to human health. Toidentify mechanistic endpoints for testing, we group chronic health outcomes associated with chemical exposure into Six Clusters of Disease (SCOD) and we propose that finished food contact articles should be tested for their impacts on these SCOD. Research should focus on developing robust, relevant, and sensitive in-vitro assays based on mechanistic information linked to the SCOD, e.g., through Adverse Outcome Pathways (AOPs) or Key Characteristics of Toxicants. Implementing this vision will improve prevention of chronic diseases that are associated with hazardous chemical exposures, including from FCMs.
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| 46. |
- Osinski, V., et al.
(författare)
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In vivo liposomal delivery of PPAR alpha/gamma dual agonist tesaglitazar in a model of obesity enriches macrophage targeting and limits liver and kidney drug effects
- 2020
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Ingår i: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 10:2, s. 585-601
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Tidskriftsartikel (refereegranskat)abstract
- Macrophages are important regulators of obesity-associated inflammation and PPAR alpha and -gamma agonism in macrophages has anti-inflammatory effects. In this study, we tested the efficacy with which liposomal delivery could target the PPAR alpha/gamma dual agonist tesaglitazar to macrophages while reducing drug action in common sites of drug toxicity: the liver and kidney, and whether tesaglitazar had anti-inflammatory effects in an in vivo model of obesity-associated dysmetabolism. Methods: Male leptin-deficient (ob/ob) mice were administered tesaglitazar or vehicle for one week in a standard oral formulation or encapsulated in liposomes. Following the end of treatment, circulating metabolic parameters were measured and pro-inflammatory adipose tissue macrophage populations were quantified by flow cytometry. Cellular uptake of liposomes in tissues was assessed using immunofluorescence and a broad panel of cell subset markers by flow cytometry. Finally, PPAR alpha/gamma gene target expression levels in the liver, kidney, and sorted macrophages were quantified to determine levels of drug targeting to and drug action in these tissues and cells. Results: Administration of a standard oral formulation of tesaglitazar effectively treated symptoms of obesity-associated dysmetabolism and reduced the number of pro-inflammatory adipose tissue macrophages. Macrophages are the major cell type that took up liposomes with many other immune and stromal cell types taking up liposomes to a lesser extent. Liposome delivery of tesaglitazar did not have effects on inflammatory macrophages nor did it improve metabolic parameters to the extent of a standard oral formulation. Liposomal delivery did, however, attenuate effects on liver weight and liver and kidney expression of PPAR alpha and -gamma gene targets compared to oral delivery. Conclusions: These findings reveal for the first time that tesaglitazar has anti-inflammatory effects on adipose tissue macrophage populations in vivo. These data also suggest that while nanoparticle delivery reduced off-target effects, yet the lack of tesaglitazar actions in non-targeted cells such (as hepatocytes and adipocytes) and the uptake of drug-loaded liposomes in many other cell types, albeit to a lesser extent, may have impacted overall therapeutic efficacy. This fulsome analysis of cellular uptake of tesaglitazar-loaded liposomes provides important lessons for future studies of liposome drug delivery.
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