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1.	Fresard, Laure, et al. (författare) Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts 2019 Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919 Tidskriftsartikel (refereegranskat)abstract It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
2.	Joshi, Peter K, et al. (författare) Directional dominance on stature and cognition in diverse human populations 2015 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462 Tidskriftsartikel (refereegranskat)abstract Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
3.	Abbafati, Cristiana, et al. (författare) 2020 Tidskriftsartikel (refereegranskat)
4.	Ade, Peter, et al. (författare) The Simons Observatory : science goals and forecasts 2019 Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2 Tidskriftsartikel (refereegranskat)abstract The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
5.	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)
6.	Scott, Robert A., et al. (författare) Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways 2012 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:9, s. 991-1005 Tidskriftsartikel (refereegranskat)abstract Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.
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.
8.	Axelsson, Tony, 1969, et al. (författare) Constructed landscapes in Zoos and Heritage 2008 Ingår i: International Journal of Heritage Studies. - 1352-7258 .- 1470-3610. ; 14:1, s. 43-59 Tidskriftsartikel (refereegranskat)
9.	Banas, Indra, et al. (författare) Spatio-functional organization in virocells of small uncultivated archaea from the deep biosphere 2023 Ingår i: The ISME Journal. - : Springer Nature. - 1751-7362 .- 1751-7370. ; 17, s. 1789-1792 Tidskriftsartikel (refereegranskat)abstract Despite important ecological roles posited for virocells (i.e., cells infected with viruses), studying individual cells in situ is technically challenging. We introduce here a novel correlative microscopic approach to study the ecophysiology of virocells. By conducting concerted virusFISH, 16S rRNA FISH, and scanning electron microscopy interrogations of uncultivated archaea, we linked morphologies of various altiarchaeal cells to corresponding phylogenetic signals and indigenous virus infections. While uninfected cells exhibited moderate separation between fluorescence signals of ribosomes and DNA, virocells displayed complete cellular segregation of chromosomal DNA from viral DNA, the latter co-localizing with host ribosome signals. A similar spatial separation was observed in dividing cells, with viral signals congregating near ribosomes at the septum. These observations suggest that replication of these uncultivated viruses occurs alongside host ribosomes, which are used to generate the required proteins for virion assembly. Heavily infected cells sometimes displayed virus-like particles attached to their surface, which agree with virus structures in cells observed via transmission electron microscopy. Consequently, this approach is the first to link genomes of uncultivated viruses to their respective structures and host cells. Our findings shed new light on the complex ecophysiology of archaeal virocells in deep subsurface biofilms and provide a solid framework for future in situ studies of virocells.
10.	Bartolini, Nadia, et al. (författare) Assembling alternative futures for heritage 2018 Ingår i: Context. - Tisbury, UK : Institute of Historic Building Conservation. - 0958-2746. ; :155, s. 22-24 Tidskriftsartikel (populärvet., debatt m.m.)
11.	Bermingham, Kate M., et al. (författare) Snack quality and snack timing are associated with cardiometabolic blood markers : the ZOE PREDICT study Ingår i: European Journal of Nutrition. - 1436-6207. Tidskriftsartikel (refereegranskat)abstract
12.	Cable, Jennifer, et al. (författare) Lessons from the pandemic : Responding to emerging zoonotic viral diseases-a Keystone Symposia report 2022 Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1518:1, s. 209-225 Tidskriftsartikel (refereegranskat)abstract The COVID-19 pandemic caught the world largely unprepared, including scientific and policy communities. On April 10-13, 2022, researchers across academia, industry, government, and nonprofit organizations met at the Keystone symposium "Lessons from the Pandemic: Responding to Emerging Zoonotic Viral Diseases" to discuss the successes and challenges of the COVID-19 pandemic and what lessons can be applied moving forward. Speakers focused on experiences not only from the COVID-19 pandemic but also from outbreaks of other pathogens, including the Ebola virus, Lassa virus, and Nipah virus. A general consensus was that investments made during the COVID-19 pandemic in infrastructure, collaborations, laboratory and manufacturing capacity, diagnostics, clinical trial networks, and regulatory enhancements-notably, in low-to-middle income countries-must be maintained and strengthened to enable quick, concerted responses to future threats, especially to zoonotic pathogens.
13.	Carter, Aarynn L., et al. (författare) A benchmark JWST near-infrared spectrum for the exoplanet WASP-39 b 2024 Ingår i: Nature Astronomy. - 2397-3366. ; In Press Tidskriftsartikel (refereegranskat)abstract A combined analysis of datasets across four JWST instrument modes provides a benchmark transmission spectrum for the Saturn-mass WASP-39 b. The broad wavelength range and high resolution constrain orbital and stellar parameters to below 1%.
14.	de Vries, Claire E. E., et al. (författare) Outcomes of the first global multidisciplinary consensus meeting including persons living with obesity to standardize patient-reported outcome measurement in obesity treatment research 2022 Ingår i: Obesity Reviews. - : John Wiley & Sons. - 1467-7881 .- 1467-789X. ; 23:8 Tidskriftsartikel (refereegranskat)abstract Quality of life is a key outcome that is not rigorously measured in obesity treatment research due to the lack of standardization of patient-reported outcomes (PROs) and PRO measures (PROMs). The S.Q.O.T. initiative was founded to Standardize Quality of life measurement in Obesity Treatment. A first face-to-face, international, multidisciplinary consensus meeting was conducted to identify the key PROs and preferred PROMs for obesity treatment research. It comprised of 35 people living with obesity (PLWO) and healthcare providers (HCPs). Formal presentations, nominal group techniques, and modified Delphi exercises were used to develop consensus-based recommendations. The following eight PROs were considered important: self-esteem, physical health/functioning, mental/psychological health, social health, eating, stigma, body image, and excess skin. Self-esteem was considered the most important PRO, particularly for PLWO, while physical health was perceived to be the most important among HCPs. For each PRO, one or more PROMs were selected, except for stigma. This consensus meeting was a first step toward standardizing PROs (what to measure) and PROMs (how to measure) in obesity treatment research. It provides an overview of the key PROs and a first selection of the PROMs that can be used to evaluate these PROs.
15.	Do, Ron, et al. (författare) Common variants associated with plasma triglycerides and risk for coronary artery disease 2013 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345- Tidskriftsartikel (refereegranskat)abstract Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
16.	Elmendorf, Sarah C., et al. (författare) Global assessment of experimental climate warming on tundra vegetation : heterogeneity over space and time 2012 Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 15:2, s. 164-175 Forskningsöversikt (refereegranskat)abstract Understanding the sensitivity of tundra vegetation to climate warming is critical to forecasting future biodiversity and vegetation feedbacks to climate. In situ warming experiments accelerate climate change on a small scale to forecast responses of local plant communities. Limitations of this approach include the apparent site-specificity of results and uncertainty about the power of short-term studies to anticipate longer term change. We address these issues with a synthesis of 61 experimental warming studies, of up to 20 years duration, in tundra sites worldwide. The response of plant groups to warming often differed with ambient summer temperature, soil moisture and experimental duration. Shrubs increased with warming only where ambient temperature was high, whereas graminoids increased primarily in the coldest study sites. Linear increases in effect size over time were frequently observed. There was little indication of saturating or accelerating effects, as would be predicted if negative or positive vegetation feedbacks were common. These results indicate that tundra vegetation exhibits strong regional variation in response to warming, and that in vulnerable regions, cumulative effects of long-term warming on tundra vegetation and associated ecosystem consequences have the potential to be much greater than we have observed to date.
17.	Elmendorf, Sarah C., et al. (författare) Plot-scale evidence of tundra vegetation change and links to recent summer warming 2012 Ingår i: Nature Climate Change. - : Nature Publishing Group. - 1758-678X .- 1758-6798. ; 2:6, s. 453-457 Tidskriftsartikel (refereegranskat)abstract Temperature is increasing at unprecedented rates across most of the tundra biome. Remote-sensing data indicate that contemporary climate warming has already resulted in increased productivity over much of the Arctic, but plot-based evidence for vegetation transformation is not widespread. We analysed change in tundra vegetation surveyed between 1980 and 2010 in 158 plant communities spread across 46 locations.We found biome-wide trends of increased height of the plant canopy and maximum observed plant height for most vascular growth forms; increased abundance of litter; increased abundance of evergreen, low-growing and tall shrubs; and decreased abundance of bare ground. Intersite comparisons indicated an association between the degree of summer warming and change in vascular plant abundance, with shrubs, forbs and rushes increasing with warming. However, the association was dependent on the climate zone, the moisture regime and the presence of permafrost. Our data provide plot-scale evidence linking changes in vascular plant abundance to local summer warming in widely dispersed tundra locations across the globe.
18.	Garcia-Martin, E. Elena, et al. (författare) Sources, Composition, and Export of Particulate Organic Matter Across British Estuaries 2023 Ingår i: Journal of Geophysical Research - Biogeosciences. - : American Geophysical Union (AGU). - 2169-8953 .- 2169-8961. ; 128:4 Tidskriftsartikel (refereegranskat)abstract Estuaries receive and process a large amount of particulate organic carbon (POC) prior to its export into coastal waters. Studying the origin of this POC is key to understanding the fate of POC and the role of estuaries in the global carbon cycle. Here, we evaluated the concentrations of POC, as well as particulate organic nitrogen (PON), and used stable carbon and nitrogen isotopes to assess their sources across 13 contrasting British estuaries during five different sampling campaigns over 1 year. We found a high variability in POC and PON concentrations across the salinity gradient, reflecting inputs, and losses of organic material within the estuaries. Catchment land cover appeared to influence the contribution of POC to the total organic carbon flux from the estuary to coastal waters, with POC contributions >36% in estuaries draining catchments with a high percentage of urban/suburban land, and <11% in estuaries draining catchments with a high peatland cover. There was no seasonal pattern in the isotopic composition of POC and PON, suggesting similar sources for each estuary over time. Carbon isotopic ratios were depleted (-26.7 +/- 0.42 parts per thousand, average +/- sd) at the lowest salinity waters, indicating mainly terrigenous POC (TPOC). Applying a two-source mixing model, we observed high variability in the contribution of TPOC at the highest salinity waters between estuaries, with a median value of 57%. Our results indicate a large transport of terrigenous organic carbon into coastal waters, where it may be buried, remineralized, or transported offshore. Plain Language Summary Estuaries transport and process a large amount terrigenous particulate organic matter (i.e., carbon and nitrogen) prior to its export to coastal waters. In order to understand the fate of organic carbon and the role of estuaries in the global carbon cycle it is essential to improve our knowledge on its composition, origin, and amount of carbon transported. We quantified the elemental concentrations and stable isotopes composition of carbon and nitrogen to quantify the amount of terrigenous particulate organic matter transported by 13 British estuaries, which drain catchments of diverse land cover under different hydrological conditions. We found a great variability in particulate organic carbon (POC) and particulate organic nitrogen concentrations across the salinity gradient, implying inputs, and losses of material within the estuaries. Each estuary had similar sources of particulate material throughout the year. In most of the estuaries, the POC had a terrigenous origin at the lowest salinity waters. The terrigenous organic carbon contribution decreased toward coastal waters with an average contribution of 57% at the highest salinity waters, indicating a large transport of terrigenous organic carbon into coastal waters.
19.	García‐Martín, E. Elena, et al. (författare) Contrasting Estuarine Processing of Dissolved Organic Matter Derived From Natural and Human‐Impacted Landscapes 2021 Ingår i: Global Biogeochemical Cycles. - : American Geophysical Union (AGU). - 0886-6236 .- 1944-9224. ; 35:10 Tidskriftsartikel (refereegranskat)
20.	Harrison, Rodney, et al. (författare) Discussion and conclusions 2020 Ingår i: Heritage Futures. - London : UCL Press. - 9781787356009 - 9781787356023 - 9781787356016 - 9781787356030 - 9781787356047 ; , s. 465-488 Bokkapitel (refereegranskat)
21.	Harrison, Rodney, et al. (författare) Heritage Futures 2016 Ingår i: Archaeology International. - : Ubiquity Press. - 1463-1725 .- 2048-4194. ; 19, s. 19-72 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Heritage Futures is a four-year collaborative international research programme (2015–2019) funded by a UK Arts and Humanities Research Council (AHRC) ‘Care for the Future’ Theme Large Grant, and supported additionally by its host universities and partner organisations. The research programme involves ambitious interdisciplinary research to explore the potential for innovation and creative exchange across a broad range of heritage and related fields, in partnership with a number of academic and non-academic institutions and interest groups. It is distinctive in its comparative approach which aims to bring heritage conservation practices of various forms into closer dialogue with the management of other material and virtual legacies such as nuclear waste management. It is also distinctive in its exploration of different forms of heritage as future-making practices. This brief paper provides an introduction to the research programme and its aims and methods.
22.	Heritage Futures : Comparative Approaches to Natural and Cultural Heritage Practices 2020 Samlingsverk (redaktörskap) (refereegranskat)abstract Preservation of natural and cultural heritage is often said to be something that is done for the future, or on behalf of future generations, but the precise relationship of such practices to the future is rarely reflected upon. Heritage Futures draws on research undertaken over four years by an interdisciplinary, international team of 16 researchers and more than 25 partner organisations to explore the role of heritage and heritage-like practices in building future worlds.Engaging broad themes such as diversity, transformation, profusion and uncertainty, Heritage Futures aims to understand how a range of conservation and preservation practices across a number of countries assemble and resource different kinds of futures, and the possibilities that emerge from such collaborative research for alternative approaches to heritage in the Anthropocene. Case studies include the cryopreservation of endangered DNA in frozen zoos, nuclear waste management, seed biobanking, landscape rewilding, social history collecting, space messaging, endangered language documentation, built and natural heritage management, domestic keeping and discarding practices, and world heritage site management.
23.	Holtorf, Cornelius, 1968-, et al. (författare) Uncertainty, collaboration and emerging issues 2020 Ingår i: Heritage Futures. - London : UCL Press. - 9781787356009 - 9781787356023 - 9781787356016 - 9781787356030 - 9781787356047 ; , s. 336-343 Bokkapitel (refereegranskat)
24.	Högberg, Anders, 1968-, et al. (författare) No future in archaeological heritage management? 2017 Ingår i: World archaeology. - : Routledge. - 0043-8243 .- 1470-1375. ; 49:5, s. 639-647 Tidskriftsartikel (refereegranskat)abstract Although the future is mentioned frequently in overarching aims and visions, and it is a major drive in the daily work of archaeological heritage managers and indeed heritage professionals more generally, it remains unclear precisely how an overall commitment to the future can best inform specific heritage practices. It seems that most archaeologists and other heritage professionals cannot easily express how they conceive of the future they work for, and how their work will impact on that future. The future tends to remain implicit in daily practice which operates in a continuing, rolling present. The authors argue that this needs to change because present-day heritage management may be much less beneficial for the future than we commonly expect.
25.	Kivimäki, Mika, et al. (författare) Association of Alcohol-Induced Loss of Consciousness and Overall Alcohol Consumption With Risk for Dementia 2020 Ingår i: JAMA Network Open. - : American Medical Association. - 2574-3805. ; 3:9 Tidskriftsartikel (refereegranskat)abstract Importance: Evidence on alcohol consumption as a risk factor for dementia usually relates to overall consumption. The role of alcohol-induced loss of consciousness is uncertain. Objective: To examine the risk of future dementia associated with overall alcohol consumption and alcohol-induced loss of consciousness in a population of current drinkers. Design, Setting, and Participants: Seven cohort studies from the UK, France, Sweden, and Finland (IPD-Work consortium) including 131 415 participants were examined. At baseline (1986-2012), participants were aged 18 to 77 years, reported alcohol consumption, and were free of diagnosed dementia. Dementia was examined during a mean follow-up of 14.4 years (range, 12.3-30.1). Data analysis was conducted from November 17, 2019, to May 23, 2020. Exposures: Self-reported overall consumption and loss of consciousness due to alcohol consumption were assessed at baseline. Two thresholds were used to define heavy overall consumption: greater than 14 units (U) (UK definition) and greater than 21 U (US definition) per week. Main Outcomes and Measures: Dementia and alcohol-related disorders to 2016 were ascertained from linked electronic health records. Results: Of the 131 415 participants (mean [SD] age, 43.0 [10.4] years; 80 344 [61.1%] women), 1081 individuals (0.8%) developed dementia. After adjustment for potential confounders, the hazard ratio (HR) was 1.16 (95% CI, 0.98-1.37) for consuming greater than 14 vs 1 to 14 U of alcohol per week and 1.22 (95% CI, 1.01-1.48) for greater than 21 vs 1 to 21 U/wk. Of the 96 591 participants with data on loss of consciousness, 10 004 individuals (10.4%) reported having lost consciousness due to alcohol consumption in the past 12 months. The association between loss of consciousness and dementia was observed in men (HR, 2.86; 95% CI, 1.77-4.63) and women (HR, 2.09; 95% CI, 1.34-3.25) during the first 10 years of follow-up (HR, 2.72; 95% CI, 1.78-4.15), after excluding the first 10 years of follow-up (HR, 1.86; 95% CI, 1.16-2.99), and for early-onset (<65 y: HR, 2.21; 95% CI, 1.46-3.34) and late-onset (≥65 y: HR, 2.25; 95% CI, 1.38-3.66) dementia, Alzheimer disease (HR, 1.98; 95% CI, 1.28-3.07), and dementia with features of atherosclerotic cardiovascular disease (HR, 4.18; 95% CI, 1.86-9.37). The association with dementia was not explained by 14 other alcohol-related conditions. With moderate drinkers (1-14 U/wk) who had not lost consciousness as the reference group, the HR for dementia was twice as high in participants who reported having lost consciousness, whether their mean weekly consumption was moderate (HR, 2.19; 95% CI, 1.42-3.37) or heavy (HR, 2.36; 95% CI, 1.57-3.54). Conclusions and Relevance: The findings of this study suggest that alcohol-induced loss of consciousness, irrespective of overall alcohol consumption, is associated with a subsequent increase in the risk of dementia.
26.	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.
27.	Kosentka, Pawel, et al. (författare) Evolution of the toxins muscarine and psilocybin in a family of mushroom-forming fungi. 2013 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:5, s. e64646- Tidskriftsartikel (refereegranskat)abstract Mushroom-forming fungi produce a wide array of toxic alkaloids. However, evolutionary analyses aimed at exploring the evolution of muscarine, a toxin that stimulates the parasympathetic nervous system, and psilocybin, a hallucinogen, have never been performed. The known taxonomic distribution of muscarine within the Inocybaceae is limited, based only on assays of species from temperate regions of the northern hemisphere. Here, we present a review of muscarine and psilocybin assays performed on species of Inocybaceae during the last fifty years. To supplement these results, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine whether muscarine was present in 30 new samples of Inocybaceae, the majority of which have not been previously assayed or that originated from either the tropics or temperate regions of the southern hemisphere. Our main objective is to test the hypothesis that the presence of muscarine is a shared ancestral feature of the Inocybaceae. In addition, we also test whether species of Inocyabceae that produce psilocybin are monophyletic. Our findings suggest otherwise. Muscarine has evolved independently on several occasions, together with several losses. We also detect at least two independent transitions of muscarine-free lineages to psilocybin-producing states. Although not ancestral for the family as a whole, muscarine is a shared derived trait for an inclusive clade containing three of the seven major lineages of Inocybaceae (the Inocybe, Nothocybe, and Pseudosperma clades), the common ancestor of which may have evolved ca. 60 million years ago. Thus, muscarine represents a conserved trait followed by several recent losses. Transitions to psilocybin from muscarine-producing ancestors occurred more recently between 10-20 million years ago after muscarine loss in two separate lineages. Statistical analyses firmly reject a single origin of muscarine-producing taxa.
28.	Lagou, Vasiliki, et al. (författare) Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability 2021 Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1 Tidskriftsartikel (refereegranskat)abstract Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
29.	Lindgren Belal, Sarah, et al. (författare) Association of PET index quantifying skeletal uptake in NaF PET/CT images with overall survival in prostate cancer patients 2017 Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 35:6 Suppl, s. 178-178 Konferensbidrag (refereegranskat)abstract Background: Bone Scan Index (BSI) derived from 2D whole-body bone scans is considered an imaging biomarker of bone metastases burden carrying prognostic information. Sodium fluoride (NaF) PET/CT is more sensitive than bone scan in detecting bone changes due to metastases. We aimed to develop a semi-quantitative PET index similar to the BSI for NaF PET/CT imaging and to study its relationship to BSI and overall survival in patients with prostate cancer.Methods: NaF PET/CT and bone scans were analyzed in 48 patients (aged 53-92 years) with prostate cancer. Thoracic and lumbar spines, sacrum, pelvis, ribs, scapulae, clavicles, and sternum were automatically segmented from the CT images, representing approximately 1/3 of the total skeletal volume. Hotspots in the PET images, within the segmented parts in the CT images, were visually classified and hotspots interpreted as metastases were included in the analysis. The PET index was defined as the quotient obtained as the hotspot volume from the PET images divided by the segmented bone tissue volume from the CT images. BSI was automatically calculated using EXINIboneBSI.Results: The correlation between the PET index and BSI was r2= 0.54. The median BSI was 0.39 (IQR 0.08-2.05). The patients with a BSI ≥ 0.39 had a significantly shorter median survival time than patients with a BSI < 0.39 (2.3 years vs. not reached after 5 years). BSI was significantly associated with overall survival (HR 1.13, 95% CI 1.13 to 1.41; p < 0.001), and the C-index was 0.68. The median PET index was 0.53 (IQR 0.02-2.62). The patients with a PET index ≥ 0.53 had a significantly shorter median survival time than patients with a PET index < 0.53 (2.5 years vs. not reached after 5 years). The PET index was significantly associated with overall survival (HR 1.18, 95% CI 1.01 to 1.30; p < 0.001) and C-index was 0.68.Conclusions: PET index based on NaF PET/CT images was correlated to BSI and significantly associated with overall survival in patients with prostate cancer. Further studies are needed to evaluate the clinical value of this novel 3D PET index as a possible future imaging biomarker.
30.	May, Sarah, et al. (författare) Uncertain futures 2020 Ingår i: Heritage Futures<em></em>. - London : UCL Press. - 9781787356009 - 9781787356023 - 9781787356016 - 9781787356030 - 9781787356047 ; , s. 263-275 Bokkapitel (refereegranskat)
31.	Naghavi, Mohsen, et al. (författare) Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013 2015 Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171 Tidskriftsartikel (refereegranskat)abstract Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
32.	Nguyen, Thanh N, et al. (författare) Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up. 2023 Ingår i: Neurology. - 1526-632X. ; 100:4 Tidskriftsartikel (refereegranskat)abstract Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
33.	Papadimitriou, Nikos, et al. (författare) Physical activity and risks of breast and colorectal cancer : a Mendelian randomisation analysis 2020 Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1 Tidskriftsartikel (refereegranskat)abstract Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value=0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value=0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers. Physical activity has been linked to lower risks of colorectal and breast cancer. Here, the authors present a Mendelian randomisation analysis supporting a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer.
34.	Penrose, Sefryn, et al. (författare) The hundred-thousand-year question : First cross-theme knowledge-exchange workshop, 8–11 March 2016, Forsmark and Stockholm, Sweden 2020 Ingår i: Heritage Futures. - London : UCL Press. - 9781787356009 - 9781787356023 - 9781787356016 - 9781787356030 - 9781787356047 ; , s. 143-151 Bokkapitel (refereegranskat)
35.	Pupkaite, Justina, et al. (författare) Collagen-Based Photoactive Agent for Tissue Bonding 2017 Ingår i: ACS Applied Materials and Interfaces. - : AMER CHEMICAL SOC. - 1944-8244 .- 1944-8252. ; 9:11, s. 9265-9270 Tidskriftsartikel (refereegranskat)abstract Using a combination of methacrylated, collagen and the photosensitizer rose Bengal, a new light-activated biomimetic material for tissue sutureless bonding was developed. This formulation was cross-linked using green light. In vivo tests in mice demonstrate the suitability of the material for sutureless wound closure.
36.	Repetto, Linda, et al. (författare) Genetic mechanisms of 184 neuro-related proteins in human plasma. 2023 Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Understanding the genetic basis of neuro-related proteins is essential for dissecting the disease etiology of neuropsychiatric disorders and other complex traits and diseases. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-related traits as well as complex diseases such as hypertension, high cholesterol, immune-related disorders, and psychiatric disorders. Integrating with established drug information, we validated 13 combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets for diseases and comorbidities. This consortium effort provides a large-scale proteogenomic resource for biomedical research.
37.	Repetto, Linda, et al. (författare) Unraveling Neuro-Proteogenomic Landscape and Therapeutic Implications for Human Behaviors and Psychiatric Disorders. 2023 Ingår i: Nature Portfolio. - : Research Square Platform LLC. Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioral traits and the disease etiology of neuropsychiatric disorders. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-related traits such as sleeping, smoking, feelings, alcohol intake, mental health, and psychiatric disorders. Integrating with established drug information, we validated 13 out of 13 matched combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets. This consortium effort provides a large-scale proteogenomic resource for biomedical research on human behaviors and other neuro-related phenotypes.
38.	Ried, Janina S., et al. (författare) A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape 2016 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7 Tidskriftsartikel (refereegranskat)abstract Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
39.	Sadik, May, 1970, et al. (författare) Automated evaluation of normal uptake in different skeletal parts using 18F-sodium fluoride (NaF) PET/CT using a new convolutional neural network method 2017 Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 44:Supplement 2, s. 479-479 Tidskriftsartikel (refereegranskat)abstract Introduction : Understanding normal skeletal uptake of 18F-sodium fluoride (18F-NaF) in positron emission tomography/computed tomography (PET/CT) is important for clinical interpretation. Quantification of tracer uptake in PET/CT is often performed by placing a volume of interest (VOI) to measure standard uptake values (SUVs). Manual placement of this VOI requires a subjective decision and can only measure uptake in a specific part of the bone. The aim of this study was to investigate normal 18F-NaF skeletal activity in patients with prostate cancer at a stage of the disease prior to development of bone metastases, by using a new method that quantifies uptake in entire skeletal parts. Material and Methods : Patients with biopsy-verified high-risk prostate cancer and a negative or inconclusive bone scintigraphy and no metastatic lesions on 18F-NaF PET/CT (performed March 2008 - June 2010) were retrospectively included (n=48). Whole-body PET scans were acquired 1-1.5 h after i.v. injection of 4 MBq/kg 18F-NaF (max 400 MBq). CT scans were obtained immediately after the PET scan. Thoracic and lumbar vertebrae, sacrum, pelvis, ribs, scapulae, clavicles and sternum were automatically segmented in the CT images, using a method based on a convolutional neural network, to obtain the volume of each skeletal region. The network was trained using a separate group of CT scans with manual segmentations. Mean and maximum SUV (SUVmean and SUVmax) were subsequently measured for each skeletal part in the PET scans. Results : Average (SD) SUVmean for the skeletal regions were: Thoracic vertebrae 0.98 (0.20), lumbar vertebrae 0.96 (0.19), sacrum 0.75 (0.15), pelvis 0.73 (0.16), ribs 0.41 (0.11), scapulae 0.46 (0.11), clavicles 0.50 (0.16) and sternum 0.61 (0.13). Average (SD) SUVmax for the skeletal regions were: Thoracic vertebrae 1.95 (0.66), lumbar vertebrae 2.10 (0.78), sacrum 2.22 (0.77), pelvis 1.99 (0.82), ribs 1.19 (0.35), scapulae 1.94 (0.98), clavicles 2.00 (1.03) and sternum 1.68 (0.44). Conclusion : We present a new method to segment and quantify uptake in skeletal regions in 18F-NaF PET/CT. Various parts of the bone have different SUVs in patients with regional prostate cancer. Vertebrae and pelvis have higher SUVs than ribs. The highest SUVmax were found in the thoracic and lumbar vertebrae. The findings are of importance for interpretation of 18F-NaF PET/CT.
40.	Sandholm, Niina, et al. (författare) New susceptibility loci associated with kidney disease in type 1 diabetes 2012 Ingår i: PLOS Genetics. - San Francisco, USA : Public Library of Science, PLOS. - 1553-7390 .- 1553-7404. ; 8:9, s. e1002921- Tidskriftsartikel (refereegranskat)abstract Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genomewide association studies (GWAS) of T1D DN comprising similar to 2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2 x 10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0 x 10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-beta 1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1 x 10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.
41.	Stattin, Pär, et al. (författare) Population-based study of disease trajectory after radical treatment for high-risk prostate cancer 2024 Ingår i: BJU International. - : John Wiley & Sons. - 1464-4096 .- 1464-410X. ; 134:1, s. 96-102 Tidskriftsartikel (refereegranskat)abstract Objectives: To investigate long-term disease trajectories among men with high-risk localized or locally advanced prostate cancer (HRLPC) treated with radical radiotherapy (RT) or radical prostatectomy (RP).Material and Methods: Men diagnosed with HRLPC in 2006–2020, who received primary RT or RP, were identified from the Prostate Cancer data Base Sweden (PCBaSe) 5.0. Follow-up ended on 30 June 2021. Treatment trajectories and risk of death from prostate cancer (PCa) or other causes were assessed by competing risk analyses using cumulative incidence for each event.Results: In total, 8317 men received RT and 4923 men underwent RP. The median (interquartile range) follow-up was 6.2 (3.6–9.5) years. After RT, the 10-year risk of PCa-related death was 0.13 (95% confidence interval [CI] 0.12–0.14) and the risk of death from all causes was 0.32 (95% CI 0.31–0.34). After RP, the 10-year risk of PCa-related death was 0.09 (95% CI 0.08–0.10) and the risk of death from all causes was 0.19 (95% CI 0.18–0.21). The 10-year risks of androgen deprivation therapy (ADT) as secondary treatment were 0.42 (95% CI 0.41–0.44) and 0.21 (95% CI 0.20–0.23) after RT and RP, respectively. Among men who received ADT as secondary treatment, the risk of PCa-related death at 10 years after initiation of ADT was 0.33 (95% CI 030–0.36) after RT and 0.27 (95% CI 0.24–0.30) after RP.Conclusion: Approximately one in 10 men with HRLPC who received primary RT or RP had died from PCa 10 years after diagnosis. Approximately one in three men who received secondary ADT, an indication of PCa progression, died from PCa 10 years after the start of ADT. Early identification and aggressive treatment of men with high risk of progression after radical treatment are warranted.
42.	Willer, Cristen J., et al. (författare) Discovery and refinement of loci associated with lipid levels 2013 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283 Tidskriftsartikel (refereegranskat)abstract Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
43.	Wollentz, Gustav, et al. (författare) Toxic heritage : Uncertain and unsafe 2020 Ingår i: Heritage Futures. - London : UCL Press. - 9781787356009 - 9781787356023 - 9781787356016 - 9781787356030 - 9781787356047 ; , s. 294-312 Bokkapitel (refereegranskat)
44.	Tabiri, S, et al. (författare) 2021 swepub:Mat__t

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