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1.
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2.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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3.
  • Blunden, Jessica, et al. (författare)
  • State of the Climate in 2012
  • 2013
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 94:8, s. S1-S258
  • Tidskriftsartikel (refereegranskat)abstract
    • For the first time in serveral years, the El Nino-Southern Oscillation did not dominate regional climate conditions around the globe. A weak La Ni a dissipated to ENSOneutral conditions by spring, and while El Nino appeared to be emerging during summer, this phase never fully developed as sea surface temperatures in the eastern conditions. Nevertheless, other large-scale climate patterns and extreme weather events impacted various regions during the year. A negative phase of the Arctic Oscillation from mid-January to early February contributed to frigid conditions in parts of northern Africa, eastern Europe, and western Asia. A lack of rain during the 2012 wet season led to the worst drought in at least the past three decades for northeastern Brazil. Central North America also experienced one of its most severe droughts on record. The Caribbean observed a very wet dry season and it was the Sahel's wettest rainy season in 50 years. Overall, the 2012 average temperature across global land and ocean surfaces ranked among the 10 warmest years on record. The global land surface temperature alone was also among the 10 warmest on record. In the upper atmosphere, the average stratospheric temperature was record or near-record cold, depending on the dataset. After a 30-year warming trend from 1970 to 1999 for global sea surface temperatures, the period 2000-12 had little further trend. This may be linked to the prevalence of La Ni a-like conditions during the 21st century. Heat content in the upper 700 m of the ocean remained near record high levels in 2012. Net increases from 2011 to 2012 were observed at 700-m to 2000-m depth and even in the abyssal ocean below. Following sharp decreases in to the effects of La Ni a, sea levels rebounded to reach records highs in 2012. The increased hydrological cycle seen in recent years continued, with more evaporation in drier locations and more precipitation in rainy areas. In a pattern that has held since 2004, salty areas of the ocean surfaces and subsurfaces were anomalously salty on average, while fresher areas were anomalously fresh. Global tropical cyclone activity during 2012 was near average, with a total of 84 storms compared with the 1981-2010 average of 89. Similar to 2010 and 2011, the North Atlantic was the only hurricane basin that experienced above-normal activity. In this basin, Sandy brought devastation to Cuba and parts of the eastern North American seaboard. All other basins experienced either near-or below-normal tropical cyclone activity. Only three tropical cyclones reached Category 5 intensity-all in Bopha became the only storm in the historical record to produce winds greater than 130 kt south of 7 N. It was also the costliest storm to affect the Philippines and killed more than 1000 residents. Minimum Arctic sea ice extent in September and Northern Hemisphere snow cover extent in June both reached new record lows. June snow cover extent is now declining at a faster rate (-17.6% per decade) than September sea ice extent (-13.0% per decade). Permafrost temperatures reached record high values in northernmost Alaska. A new melt extent record occurred on 11-12 July on the Greenland ice sheet; 97% of the ice sheet showed some form of melt, four times greater than the average melt for this time of year. The climate in Antarctica was relatively stable overall. The largest maximum sea ice extent since records begain in 1978 was observed in September 2012. In the stratosphere, warm air led to the second smallest ozone hole in the past two decades. Even so, the springtime ozone layer above Antarctica likely will not return to its early 1980s state until about 2060. Following a slight decline associated with the global 2 emissions from fossil fuel combustion and cement production reached a record 9.5 +/- 0.5 Pg C in 2011 and a new record of 9.7 +/- 0.5 Pg C is estimated for 2012. Atmospheric CO2 concentrations increased by 2.1 ppm in 2012, to 392.6 ppm. In spring 2012, 2 concentration exceeded 400 ppm at 7 of the 13 Arctic observation sites. Globally, other greenhouse gases including methane and nitrous oxide also continued to rise in concentration and the combined effect now represents a 32% increase in radiative forcing over a 1990 baseline. Concentrations of most ozone depleting substances continued to fall.
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4.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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5.
  • Kanai, M, et al. (författare)
  • 2023
  • swepub:Mat__t
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6.
  • Arndt, D. S., et al. (författare)
  • STATE OF THE CLIMATE IN 2017
  • 2018
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
  • Forskningsöversikt (refereegranskat)
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7.
  • Arndt, D. S., et al. (författare)
  • State of the Climate in 2016
  • 2017
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
  • 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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8.
  • Turcot, Valerie, et al. (författare)
  • Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
  • 2018
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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9.
  • Marouli, Eirini, et al. (författare)
  • Rare and low-frequency coding variants alter human adult height
  • 2017
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
  • Tidskriftsartikel (refereegranskat)abstract
    • Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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10.
  • Ades, M., et al. (författare)
  • Global Climate : in State of the climate in 2019
  • 2020
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 101:8, s. S17-S127
  • Tidskriftsartikel (refereegranskat)
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11.
  • Ades, M., et al. (författare)
  • GLOBAL CLIMATE
  • 2020
  • Ingår i: BULLETIN OF THE AMERICAN METEOROLOGICAL SOCIETY. - 0003-0007 .- 1520-0477. ; 101:8
  • Tidskriftsartikel (refereegranskat)
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12.
  • Clark, Andrew G., et al. (författare)
  • Evolution of genes and genomes on the Drosophila phylogeny
  • 2007
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
  • Tidskriftsartikel (refereegranskat)abstract
    • Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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13.
  • Hillier, Ladeana W, et al. (författare)
  • Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
  • 2004
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
  • Tidskriftsartikel (refereegranskat)abstract
    • We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
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14.
  • Hudson, Lawrence N, et al. (författare)
  • The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
  • 2017
  • Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
  • Tidskriftsartikel (refereegranskat)abstract
    • The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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15.
  • Abolfathi, Bela, et al. (författare)
  • The LSST DESC DC2 Simulated Sky Survey
  • 2021
  • Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 253:31
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe the simulated sky survey underlying the second data challenge (DC2) carried out in preparation for analysis of the Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST) by the LSST Dark Energy Science Collaboration (LSST DESC). Significant connections across multiple science domains will be a hallmark of LSST; the DC2 program represents a unique modeling effort that stresses this interconnectivity in a way that has not been attempted before. This effort encompasses a full end-to-end approach: starting from a large N-body simulation, through setting up LSST-like observations including realistic cadences, through image simulations, and finally processing with Rubin's LSST Science Pipelines. This last step ensures that we generate data products resembling those to be delivered by the Rubin Observatory as closely as is currently possible. The simulated DC2 sky survey covers six optical bands in a wide-fast-deep area of approximately 300 deg2, as well as a deep drilling field of approximately 1 deg2. We simulate 5 yr of the planned 10 yr survey. The DC2 sky survey has multiple purposes. First, the LSST DESC working groups can use the data set to develop a range of DESC analysis pipelines to prepare for the advent of actual data. Second, it serves as a realistic test bed for the image processing software under development for LSST by the Rubin Observatory. In particular, simulated data provide a controlled way to investigate certain image-level systematic effects. Finally, the DC2 sky survey enables the exploration of new scientific ideas in both static and time domain cosmology.
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16.
  • Ademuyiwa, Adesoji O., et al. (författare)
  • Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
  • 2016
  • Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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17.
  • Blunden, Jessica, et al. (författare)
  • State of the climate in 2013
  • 2014
  • Ingår i: Bulletin of the American Meteorological Society. - 0003-0007. ; 95
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2014, American Meteorological Society. All rights reserved. In 2013, the vast majority of the monitored climate variables reported here maintained trends established in recent decades. ENSO was in a neutral state during the entire year, remaining mostly on the cool side of neutral with modest impacts on regional weather patterns around the world. This follows several years dominated by the effects of either La Niña or El Niño events. According to several independent analyses, 2013 was again among the 10 warmest years on record at the global scale, both at the Earth’s surface and through the troposphere. Some regions in the Southern Hemisphere had record or near-record high temperatures for the year. Australia observed its hottest year on record, while Argentina and New Zealand reported their second and third hottest years, respectively. In Antarctica, Amundsen-Scott South Pole Station reported its highest annual temperature since records began in 1957. At the opposite pole, the Arctic observed its seventh warmest year since records began in the early 20th century. At 20-m depth, record high temperatures were measured at some permafrost stations on the North Slope of Alaska and in the Brooks Range. In the Northern Hemisphere extratropics, anomalous meridional atmospheric circulation occurred throughout much of the year, leading to marked regional extremes of both temperature and precipitation. Cold temperature anomalies during winter across Eurasia were followed by warm spring temperature anomalies, which were linked to a new record low Eurasian snow cover extent in May. Minimum sea ice extent in the Arctic was the sixth lowest since satellite observations began in 1979. Including 2013, all seven lowest extents on record have occurred in the past seven years. Antarctica, on the other hand, had above-average sea ice extent throughout 2013, with 116 days of new daily high extent records, including a new daily maximum sea ice area of 19.57 million km2 reached on 1 October. ENSO-neutral conditions in the eastern central Pacific Ocean and a negative Pacific decadal oscillation pattern in the North Pacific had the largest impacts on the global sea surface temperature in 2013. The North Pacific reached a historic high temperature in 2013 and on balance the globally-averaged sea surface temperature was among the 10 highest on record. Overall, the salt content in nearsurface ocean waters increased while in intermediate waters it decreased. Global mean sea level continued to rise during 2013, on pace with a trend of 3.2 mm yr-1 over the past two decades. A portion of this trend (0.5 mm yr-1) has been attributed to natural variability associated with the Pacific decadal oscillation as well as to ongoing contributions from the melting of glaciers and ice sheets and ocean warming. Global tropical cyclone frequency during 2013 was slightly above average with a total of 94 storms, although the North Atlantic Basin had its quietest hurricane season since 1994. In the Western North Pacific Basin, Super Typhoon Haiyan, the deadliest tropical cyclone of 2013, had 1-minute sustained winds estimated to be 170 kt (87.5 m s-1) on 7 November, the highest wind speed ever assigned to a tropical cyclone. High storm surge was also associated with Haiyan as it made landfall over the central Philippines, an area where sea level is currently at historic highs, increasing by 200 mm since 1970. In the atmosphere, carbon dioxide, methane, and nitrous oxide all continued to increase in 2013. As in previous years, each of these major greenhouse gases once again reached historic high concentrations. In the Arctic, carbon dioxide and methane increased at the same rate as the global increase. These increases are likely due to export from lower latitudes rather than a consequence of increases in Arctic sources, such as thawing permafrost. At Mauna Loa, Hawaii, for the first time since measurements began in 1958, the daily average mixing ratio of carbon dioxide exceeded 400 ppm on 9 May. The state of these variables, along with dozens of others, and the 2013 climate conditions of regions around the world are discussed in further detail in this 24th edition of the State of the Climate series.
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18.
  • Craddock, Nick, et al. (författare)
  • Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
  • Tidskriftsartikel (refereegranskat)abstract
    • Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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19.
  • Ikram, M. Arfan, et al. (författare)
  • Common variants at 6q22 and 17q21 are associated with intracranial volume
  • 2012
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 539-544
  • Tidskriftsartikel (refereegranskat)abstract
    • During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 x 10(-3) for 6q22 and 1.2 x 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.
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20.
  • Justice, Anne E., et al. (författare)
  • Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
  • 2019
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
  • Tidskriftsartikel (refereegranskat)abstract
    • Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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21.
  • Taal, H. Rob, et al. (författare)
  • Common variants at 12q15 and 12q24 are associated with infant head circumference
  • 2012
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 532-538
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
  •  
22.
  • Weinstein, John N., et al. (författare)
  • The cancer genome atlas pan-cancer analysis project
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:10, s. 1113-1120
  • Tidskriftsartikel (refereegranskat)abstract
    • The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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23.
  • Horikoshi, Momoko, et al. (författare)
  • New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
  •  
24.
  • Alimena, Juliette, et al. (författare)
  • Searching for long-lived particles beyond the Standard Model at the Large Hadron Collider
  • 2020
  • Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton-proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments-as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER-to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.
  •  
25.
  • Anderson, Cynthia M., et al. (författare)
  • Permanent Genetic Resources added to Molecular Ecology Resources Database 1 December 2009-31 January 2010
  • 2010
  • Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:3, s. 576-579
  • Tidskriftsartikel (refereegranskat)abstract
    • This article documents the addition of 220 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Allanblackia floribunda, Amblyraja radiata, Bactrocera cucurbitae, Brachycaudus helichrysi, Calopogonium mucunoides, Dissodactylus primitivus, Elodea canadensis, Ephydatia fluviatilis, Galapaganus howdenae howdenae, Hoplostethus atlanticus, Ischnura elegans, Larimichthys polyactis, Opheodrys vernalis, Pelteobagrus fulvidraco, Phragmidium violaceum, Pistacia vera, and Thunnus thynnus. These loci were cross-tested on the following species: Allanblackia gabonensis, Allanblackia stanerana, Neoceratitis cyanescens, Dacus ciliatus, Dacus demmerezi, Bactrocera zonata, Ceratitis capitata, Ceratitis rosa, Ceratits catoirii, Dacus punctatifrons, Ephydatia mulleri, Spongilla lacustris, Geodia cydonium, Axinella sp., Ischnura graellsii, Ischnura ramburii, Ischnura pumilio, Pistacia integerrima and Pistacia terebinthus.
  •  
26.
  • Jones, Lesley, et al. (författare)
  • Convergent genetic and expression data implicate immunity in Alzheimer's disease
  • 2015
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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27.
  • Li, Cai, et al. (författare)
  • Two Antarctic penguin genomes reveal insights into their evolutionary history and molecular changes related to the Antarctic environment
  • 2014
  • Ingår i: GigaScience. - 2047-217X. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Penguins are flightless aquatic birds widely distributed in the Southern Hemisphere. The distinctive morphological and physiological features of penguins allow them to live an aquatic life, and some of them have successfully adapted to the hostile environments in Antarctica. To study the phylogenetic and population history of penguins and the molecular basis of their adaptations to Antarctica, we sequenced the genomes of the two Antarctic dwelling penguin species, the Adelie penguin [Pygoscelis adeliae] and emperor penguin [Aptenodytes forsteri]. Results: Phylogenetic dating suggests that early penguins arose similar to 60 million years ago, coinciding with a period of global warming. Analysis of effective population sizes reveals that the two penguin species experienced population expansions from similar to 1 million years ago to similar to 100 thousand years ago, but responded differently to the climatic cooling of the last glacial period. Comparative genomic analyses with other available avian genomes identified molecular changes in genes related to epidermal structure, phototransduction, lipid metabolism, and forelimb morphology. Conclusions: Our sequencing and initial analyses of the first two penguin genomes provide insights into the timing of penguin origin, fluctuations in effective population sizes of the two penguin species over the past 10 million years, and the potential associations between these biological patterns and global climate change. The molecular changes compared with other avian genomes reflect both shared and diverse adaptations of the two penguin species to the Antarctic environment.
  •  
28.
  • van Diepen, Sean, et al. (författare)
  • Prognostic relevance of baseline pro- and anti-inflammatory markers in STEMI : An APEX AMI substudy
  • 2013
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 168:3, s. 2127-2133
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Plaque rupture, acute ischemia, and necrosis in acute coronary syndromes are accompanied by concurrent pro-and anti-inflammatory cascades. Whether STEMI clinical prediction models can be improved with the addition of baseline inflammatory biomarkers remains unknown. Methods: In an APEX-AMI trial substudy, 772 patients had a panel of 9 inflammatory serum biomarkers, high sensitivity C reactive protein (hsCRP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measured at baseline after randomization. Baseline biomarkers were incorporated into a clinical prediction model for a composite of 90-day death, shock, or heart failure. Incremental prognostic value was assessed using Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI). Results: Individually, several biomarkers were independent predictors of clinical outcome: hsCRP (hazard ratio [HR] 1.12; 95% confidence interval [CI], 1.03-1.21; p=0.007, per doubling), NT-proBNP (HR 1.14; 95% CI, 1.06-1.23; p<0.001, per doubling), interleukin (IL)-6 (HR 1.26; 95% CI, 1.12-1.41; p<0.001, per doubling), and inducible protein-10 (IP-10) (HR 0.86; 95% CI, 0.76-0.98; p<0.025, per doubling). The addition of baseline NT-proBNP (NRI 8.6%, p=0.028; IDI 0.030, p<0.001) and IL-6 (NRI 8.8%, p=0.012; IDI 0.036, p<0.001) improved the clinical risk prediction model and the addition of hsCRP (NRI 6.5%, p=0.069; IDI 0.018, p=0.004) yielded minimal improvement. After incorporating NT-proBNP into the model, the remaining biomarkers added little additional predictive value. Conclusions: Multiple inflammatory biomarkers independently predicted 90-day death, shock or heart failure; however, they added little value to a clinical prediction model that included NT-proBNP. Future studies of inflammatory biomarkers in STEMI should report incremental value in a prediction model that includes NT-proBNP.
  •  
29.
  • Wang, Anqi, et al. (författare)
  • Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
  • 2023
  • Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
  • Tidskriftsartikel (refereegranskat)abstract
    • The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
  •  
30.
  • Akiyama, Kazunori, et al. (författare)
  • First Sagittarius A* Event Horizon Telescope Results. II. EHT and Multiwavelength Observations, Data Processing, and Calibration
  • 2022
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present Event Horizon Telescope (EHT) 1.3 mm measurements of the radio source located at the position of the supermassive black hole Sagittarius A* (Sgr A*), collected during the 2017 April 5-11 campaign. The observations were carried out with eight facilities at six locations across the globe. Novel calibration methods are employed to account for Sgr A*'s flux variability. The majority of the 1.3 mm emission arises from horizon scales, where intrinsic structural source variability is detected on timescales of minutes to hours. The effects of interstellar scattering on the image and its variability are found to be subdominant to intrinsic source structure. The calibrated visibility amplitudes, particularly the locations of the visibility minima, are broadly consistent with a blurred ring with a diameter of similar to 50 mu as, as determined in later works in this series. Contemporaneous multiwavelength monitoring of Sgr A* was performed at 22, 43, and 86 GHz and at near-infrared and X-ray wavelengths. Several X-ray flares from Sgr A* are detected by Chandra, one at low significance jointly with Swift on 2017 April 7 and the other at higher significance jointly with NuSTAR on 2017 April 11. The brighter April 11 flare is not observed simultaneously by the EHT but is followed by a significant increase in millimeter flux variability immediately after the X-ray outburst, indicating a likely connection in the emission physics near the event horizon. We compare Sgr A*'s broadband flux during the EHT campaign to its historical spectral energy distribution and find that both the quiescent emission and flare emission are consistent with its long-term behavior.
  •  
31.
  • Arridge, Christopher S., et al. (författare)
  • Uranus Pathfinder : exploring the origins and evolution of Ice Giant planets
  • 2012
  • Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 33:2-3, s. 753-791
  • Tidskriftsartikel (refereegranskat)abstract
    • The "Ice Giants" Uranus and Neptune are a different class of planet compared to Jupiter and Saturn. Studying these objects is important for furthering our understanding of the formation and evolution of the planets, and unravelling the fundamental physical and chemical processes in the Solar System. The importance of filling these gaps in our knowledge of the Solar System is particularly acute when trying to apply our understanding to the numerous planetary systems that have been discovered around other stars. The Uranus Pathfinder (UP) mission thus represents the quintessential aspects of the objectives of the European planetary community as expressed in ESA's Cosmic Vision 2015-2025. UP was proposed to the European Space Agency's M3 call for medium-class missions in 2010 and proposed to be the first orbiter of an Ice Giant planet. As the most accessible Ice Giant within the M-class mission envelope Uranus was identified as the mission target. Although not selected for this call the UP mission concept provides a baseline framework for the exploration of Uranus with existing low-cost platforms and underlines the need to develop power sources suitable for the outer Solar System. The UP science case is based around exploring the origins, evolution, and processes at work in Ice Giant planetary systems. Three broad themes were identified: (1) Uranus as an Ice Giant, (2) An Ice Giant planetary system, and (3) An asymmetric magnetosphere. Due to the long interplanetary transfer from Earth to Uranus a significant cruise-phase science theme was also developed. The UP mission concept calls for the use of a Mars Express/Rosetta-type platform to launch on a Soyuz-Fregat in 2021 and entering into an eccentric polar orbit around Uranus in the 2036-2037 timeframe. The science payload has a strong heritage in Europe and beyond and requires no significant technology developments.
  •  
32.
  • Barna, Barnabas, et al. (författare)
  • SN 2019muj-a well-observed Type Iax supernova that bridges the luminosity gap of the class
  • 2021
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 501:1, s. 1078-1099
  • Tidskriftsartikel (refereegranskat)abstract
    • We present early-time (t < +50 d) observations of SN 2019muj (=ASASSN-19tr), one of the best-observed members of the peculiar SN Iax class. Ultraviolet and optical photometric and optical and near-infrared spectroscopic follow-up started from similar to 5 d before maximum light [t(max)(B) on 58707.8 MJD] and covers the photospheric phase. The early observations allow us to estimate the physical properties of the ejecta and characterize the possible divergence from a uniform chemical abundance structure. The estimated bolometric light-curve peaks at 1.05 x 10(42) erg s(-1) and indicates that only 0.031 M-circle dot of Ni-56 was produced, making SN 2019muj a moderate luminosity object in the Iax class with peak absolute magnitude of M-V = -16.4 mag. The estimated date of explosion is t(0) = 58698.2 MJD and implies a short rise time of t(rise) = 9.6 d in B band. We fit of the spectroscopic data by synthetic spectra, calculated via the radiative transfer code TARDIS. Adopting the partially stratified abundance template based on brighter SNe Iax provides a good match with SN 2019muj. However, without earlier spectra, the need for stratification cannot be stated in most of the elements, except carbon, which is allowed to appear in the outer layers only. SN 2019muj provides a unique opportunity to link extremely low-luminosity SNe Iax to well-studied, brighter SNe Iax.
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33.
  • Barnes, Paul W., et al. (författare)
  • Ozone depletion, ultraviolet radiation, climate change and prospects for a sustainable future
  • 2019
  • Ingår i: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 2:7, s. 569-579
  • Forskningsöversikt (refereegranskat)abstract
    • © 2019, Springer Nature Limited. Changes in stratospheric ozone and climate over the past 40-plus years have altered the solar ultraviolet (UV) radiation conditions at the Earth’s surface. Ozone depletion has also contributed to climate change across the Southern Hemisphere. These changes are interacting in complex ways to affect human health, food and water security, and ecosystem services. Many adverse effects of high UV exposure have been avoided thanks to the Montreal Protocol with its Amendments and Adjustments, which have effectively controlled the production and use of ozone-depleting substances. This international treaty has also played an important role in mitigating climate change. Climate change is modifying UV exposure and affecting how people and ecosystems respond to UV; these effects will become more pronounced in the future. The interactions between stratospheric ozone, climate and UV radiation will therefore shift over time; however, the Montreal Protocol will continue to have far-reaching benefits for human well-being and environmental sustainability.
  •  
34.
  • Conti, David, V, et al. (författare)
  • Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
  • 2021
  • Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
  • Tidskriftsartikel (refereegranskat)abstract
    • Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
  •  
35.
  • Escott-Price, Valentina, et al. (författare)
  • Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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36.
  • Hosseinzadeh, Griffin, et al. (författare)
  • Weak Mass Loss from the Red Supergiant Progenitor of the Type II SN 2021yja
  • 2022
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 935:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present high-cadence optical, ultraviolet (UV), and near-infrared data of the nearby (D approximate to 23 Mpc) Type II supernova (SN) 2021yja. Many Type II SNe show signs of interaction with circumstellar material (CSM) during the first few days after explosion, implying that their red supergiant (RSG) progenitors experience episodic or eruptive mass loss. However, because it is difficult to discover SNe early, the diversity of CSM configurations in RSGs has not been fully mapped. SN 2021yja, first detected within approximate to 5.4 hours of explosion, shows some signatures of CSM interaction (high UV luminosity and radio and x-ray emission) but without the narrow emission lines or early light-curve peak that can accompany CSM. Here we analyze the densely sampled early light curve and spectral series of this nearby SN to infer the properties of its progenitor and CSM. We find that the most likely progenitor was an RSG with an extended envelope, encompassed by low-density CSM. We also present archival Hubble Space Telescope imaging of the host galaxy of SN 2021yja, which allows us to place a stringent upper limit of less than or similar to 9 M-circle dot; on the progenitor mass. However, this is in tension with some aspects of the SN evolution, which point to a more massive progenitor. Our analysis highlights the need to consider progenitor structure when making inferences about CSM properties, and that a comprehensive view of CSM tracers should be made to give a fuller view of the last years of RSG evolution.
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37.
  • Pang, Andy W., et al. (författare)
  • Towards a comprehensive structural variation map of an individual human genome
  • 2010
  • Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-7596 .- 1465-6906. ; 11:5, s. R52-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Several genomes have now been sequenced, with millions of genetic variants annotated. While significant progress has been made in mapping single nucleotide polymorphisms (SNPs) and small (< 10 bp) insertion/deletions (indels), the annotation of larger structural variants has been less comprehensive. It is still unclear to what extent a typical genome differs from the reference assembly, and the analysis of the genomes sequenced to date have shown varying results for copy number variation (CNV) and inversions. Results: We have combined computational re-analysis of existing whole genome sequence data with novel microarray-based analysis, and detect 12,178 structural variants covering 40.6 Mb that were not reported in the initial sequencing of the first published personal genome. We estimate a total non-SNP variation content of 48.8 Mb in a single genome. Our results indicate that this genome differs from the consensus reference sequence by approximately 1.2% when considering indels/CNVs, 0.1% by SNPs and approximately 0.3% by inversions. The structural variants impact 4,867 genes, and >24% of structural variants would not be imputed by SNP-association. Conclusions: Our results indicate that a large number of structural variants have been unreported in the individual genomes published to date. This significant extent and complexity of structural variants, as well as the growing recognition of their medical relevance, necessitate they be actively studied in health-related analyses of personal genomes. The new catalogue of structural variants generated for this genome provides a crucial resource for future comparison studies.
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38.
  • Sako, Masao, et al. (författare)
  • The Data Release of the Sloan Digital Sky Survey-II Supernova Survey
  • 2018
  • Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 130:988
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper describes the data release of the Sloan Digital Sky Survey-II (SDSS-II) Supernova Survey conducted between 2005 and 2007. Light curves, spectra, classifications, and ancillary data are presented for 10,258 variable and transient sources discovered through repeat ugriz imaging of SDSS Stripe 82, a 300 deg(2) area along the celestial equator. This data release is comprised of all transient sources brighter than r similar or equal to 22.5 mag with no history of variability prior to 2004. Dedicated spectroscopic observations were performed on a subset of 889 transients, as well as spectra for thousands of transient host galaxies using the SDSS-III BOSS spectrographs. Photometric classifications are provided for the candidates with good multi-color light curves that were not observed spectroscopically, using host galaxy redshift information when available. From these observations, 4607 transients are either spectroscopically confirmed, or likely to be, supernovae, making this the largest sample of supernova candidates ever compiled. We present a new method for SN host-galaxy identification and derive host-galaxy properties including stellar masses, star formation rates, and the average stellar population ages from our SDSS multi-band photometry. We derive SALT2 distance moduli for a total of 1364 SN. Ia with spectroscopic redshifts as well as photometric redshifts for a further 624 purely photometric SN. Ia candidates. Using the spectroscopically confirmed subset of the three-year SDSS-II SN. Ia sample and assuming a flat.CDM cosmology, we determine Omega(M) = 0.315 +/- 0.093 (statistical error only) and detect a non-zero cosmological constant at 5.7 sigma.
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39.
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40.
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41.
  • Ginsburg, Adam, et al. (författare)
  • astroquery: An Astronomical Web-querying Package in Python
  • 2019
  • Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 157:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Astroquery is a collection of tools for requesting data from databases hosted on remote servers with interfaces exposed on the Internet, including those with web pages but without formal application program interfaces. These tools are built on the Python requests package, which is used to make HTTP requests, and astropy, which provides most of the data parsing functionality. astroquery modules generally attempt to replicate the web page interface provided by a given service as closely as possible, making the transition from browser-based to command-line interaction easy. astroquery has received significant contributions from throughout the astronomical community, including several from telescope archives. astroquery enables the creation of fully reproducible workflows from data acquisition through publication. This paper describes the philosophy, basic structure, and development model of the astroquery package. The complete documentation for astroquery can be found at http://astroquery.readthedocs.io/.
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42.
  • Jelenkovic, Aline, et al. (författare)
  • Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age : A Study of the CODATwins Project
  • 2015
  • Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:5, s. 557-570
  • Tidskriftsartikel (refereegranskat)abstract
    • A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m(2) in childhood and adolescence and up to 0.2 kg/m(2) in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
  •  
43.
  • Lai, Qiwen, et al. (författare)
  • Hydrogen Storage Materials for Mobile and Stationary Applications : Current State of the Art
  • 2015
  • Ingår i: ChemSusChem. - : Wiley. - 1864-5631 .- 1864-564X. ; 8:17, s. 2789-2825
  • Tidskriftsartikel (refereegranskat)abstract
    • One of the limitations to the widespread use of hydrogen as an energy carrier is its storage in a safe and compact form. Herein, recent developments in effective high-capacity hydrogen storage materials are reviewed, with a special emphasis on light compounds, including those based on organic porous structures, boron, nitrogen, and aluminum. These elements and their related compounds hold the promise of high, reversible, and practical hydrogen storage capacity for mobile applications, including vehicles and portable power equipment, but also for the large scale and distributed storage of energy for stationary applications. Current understanding of the fundamental principles that govern the interaction of hydrogen with these light compounds is summarized, as well as basic strategies to meet practical targets of hydrogen uptake and release. The limitation of these strategies and current understanding is also discussed and new directions proposed.
  •  
44.
  • Lindblad-Toh, Kerstin, et al. (författare)
  • A high-resolution map of human evolutionary constraint using 29 mammals
  • 2011
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 478:7370, s. 476-482
  • Tidskriftsartikel (refereegranskat)abstract
    • The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering similar to 4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for similar to 60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate-and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.
  •  
45.
  • Liu, Xueping, et al. (författare)
  • Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.
  • 2019
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P=3.96×10-14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.
  •  
46.
  • Munshi, Pashna N., et al. (författare)
  • American Society of Transplantation and Cellular Therapy, Center of International Blood and Marrow Transplant Research, and European Society for Blood and Marrow Transplantation Clinical Practice Recommendations for Transplantation and Cellular Therapies in Mantle Cell Lymphoma
  • 2021
  • Ingår i: Transplantation and cellular therapy. - : Elsevier BV. - 2666-6367. ; 27:9, s. 720-728
  • Tidskriftsartikel (refereegranskat)abstract
    • Autologous (auto-) and allogeneic (allo-) hematopoietic cell transplantation (HCT) are accepted treatment modalities in contemporary treatment algorithms for mantle cell lymphoma (MCL). Chimeric antigen receptor (CAR) T cell therapy recently received approval for MCL; however, its exact place and sequence in relation to HCT remain unclear. The American Society of Transplantation and Cellular Therapy, Center of International Blood and Marrow Transplant Research, and the European Society for Blood and Marrow Transplantation jointly convened an expert panel to formulate consensus recommendations for role, timing, and sequencing of auto-HCT, allo-HCT, and CAR T cell therapy for patients with newly diagnosed and relapsed/refractory (R/R) MCL. The RAND-modified Delphi method was used to generate consensus statements. Seventeen consensus statements were generated, with a few key statements as follows: in the first line setting, auto-HCT consolidation represents standard of care in eligible patients, whereas there is no clear role of allo-HCT or CAR T cell therapy outside of clinical trials. In the R/R setting, the preferential option is CAR T cell therapy, especially in patients with MCL failing or intolerant to at least one Bruton's tyrosine kinase inhibitor, while allo-HCT is recommended if CAR T cell therapy fails or is infeasible. Several recommendations were based on expert opinion, where the panel developed consensus statements for important real-world clinical scenarios to guide clinical practice. In the absence of contemporary evidence-based data, the panel found RAND-modified Delphi methodology effective in providing a formal framework for developing consensus recommendations for the timing and sequence of cellular therapies for MCL.
  •  
47.
  • Munshi, Pashna N., et al. (författare)
  • ASTCT, CIBMTR, and EBMT clinical practice recommendations for transplant and cellular therapies in mantle cell lymphoma
  • 2021
  • Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 56:12, s. 2911-2921
  • Tidskriftsartikel (refereegranskat)abstract
    • Autologous (auto-) or allogeneic (allo-) hematopoietic cell transplantation (HCT) are accepted treatment modalities for mantle cell lymphoma (MCL). Recently, chimeric antigen receptor (CAR) T-cell therapy received approval for MCL; however, its exact place and sequence in relation to HCT is unclear. The ASTCT, CIBMTR, and the EBMT, jointly convened an expert panel to formulate consensus recommendations for role, timing, and sequencing of auto-, allo-HCT, and CAR T-cell therapy for patients with newly diagnosed and relapsed/refractory (R/R) MCL. The RAND-modified Delphi method was used to generate consensus statements. Seventeen consensus statements were generated; in the first-line setting auto-HCT consolidation represents standard-of-care in eligible patients, whereas there is no clear role of allo-HCT or CAR T-cell therapy, outside of a clinical trial. In the R/R setting, the preferential option is CAR T-cell therapy especially in MCL failing or intolerant to at least one Bruton’s tyrosine kinase inhibitor, while allo-HCT is recommended if CAR T-cell therapy has failed or is not feasible. In the absence of contemporary evidence-based data, the panel found RAND-modified Delphi methodology effective in providing a formal framework for developing consensus recommendations for the timing and sequence of cellular therapies for MCL.
  •  
48.
  • Patterson, Nick, et al. (författare)
  • Large-scale migration into Britain during the Middle to Late Bronze Age
  • 2022
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
  • Tidskriftsartikel (refereegranskat)abstract
    • Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
  •  
49.
  • Robson, T. Matthew, et al. (författare)
  • A perspective on ecologically relevant plant-UV research and its practical application
  • 2019
  • Ingår i: Photochemical and Photobiological Sciences. - : Royal Society of Chemistry. - 1474-905X .- 1474-9092. ; 18:5, s. 970-988
  • Tidskriftsartikel (refereegranskat)abstract
    • Plants perceive ultraviolet-B (UV-B) radiation through the UV-B photoreceptor UV RESISTANCE LOCUS 8 (UVR8), and initiate regulatory responses via associated signalling networks, gene expression and metabolic pathways. Various regulatory adaptations to UV-B radiation enable plants to harvest information about fluctuations in UV-B irradiance and spectral composition in natural environments, and to defend themselves against UV-B exposure. Given that UVR8 is present across plant organs and tissues, knowledge of the systemic signalling involved in its activation and function throughout the plant is important for understanding the context of specific responses. Fine-scale understanding of both UV-B irradiance and perception within tissues and cells requires improved application of knowledge about UV-attenuation in leaves and canopies, warranting greater consideration when designing experiments. In this context, reciprocal crosstalk among photoreceptor-induced pathways also needs to be considered, as this appears to produce particularly complex patterns of physiological and morphological response. Through crosstalk, plant responses to UV-B radiation go beyond simply UV-protection or amelioration of damage, but may give cross-protection over a suite of environmental stressors. Overall, there is emerging knowledge showing how information captured by UVR8 is used to regulate molecular and physiological processes, although understanding of upscaling to higher levels of organisation, i.e. organisms, canopies and communities remains poor. Achieving this will require further studies using model plant species beyond Arabidopsis, and that represent a broad range of functional types. More attention should also be given to plants in natural environments in all their complexity, as such studies are needed to acquire an improved understanding of the impact of climate change in the context of plant-UV responses. Furthermore, broadening the scope of experiments into the regulation of plant-UV responses will facilitate the application of UV radiation in commercial plant production. By considering the progress made in plant-UV research, this perspective highlights prescient topics in plant-UV photobiology where future research efforts can profitably be focussed. This perspective also emphasises burgeoning interdisciplinary links that will assist in understanding of UV-B effects across organisational scales and gaps in knowledge that need to be filled so as to achieve an integrated vision of plant responses to UV-radiation.
  •  
50.
  • Sheshadri, Veena, et al. (författare)
  • Simulation capacity building in rural Indian hospitals : A 1-year follow-up qualitative analysis
  • 2021
  • Ingår i: BMJ Simulation and Technology Enhanced Learning. - : BMJ. - 2056-6697. ; 7:3, s. 140-145
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The benefits of simulation-based medical training are well described. The most effective way to plant and scale simulation training in rural locations remains undescribed. We sought to plant simulation training programmes for anaesthesia emergencies in two rural Indian hospitals. Methods: Two Indian consultant anaesthetists without experience in medical simulation underwent a 3-day course at the Boston Children's Hospital's (BCH) Simulator Program. They returned to their institutions and launched simulation programmes with an airway manikin and mock patient monitor. The 1-year experience was evaluated using individual, in-depth interviews of simulation facilitators. Three staff members (responsible for facilitating medical simulations over the prior year) at two rural hospitals in India were interviewed. None attended the BCH training; instead, they received on-the-job training from the BCH-trained, consultant anaesthetist colleagues. Results: Successes included organisational adoption of simulation training with exercises 1 year after the initial BCH-training, increased interdisciplinary teamwork and improved clinical competency in managing emergencies. Barriers to effective, local implementation of simulation programmes fell into three categories: time required to run simulations, fixed and rigid roles, and variable resources. Thematic improvement requests were for standardised resources to help train simulation facilitators and demonstrate to participants a well-run simulation, in addition to context-sensitive scenarios. Conclusion: An in-person training of simulation facilitators to promote medical simulation programmes in rural hospitals produced ongoing simulation programmes 1 year later. In order to make these programmes sustainable, however, increased investment in developing simulation facilitators is required. In particular, simulation facilitators must be prepared to formally train other simulation facilitators, too.
  •  
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