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1.	2021 swepub:Mat__t
2.	Ederle, Joerg, et al. (författare) Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial 2010 Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997 Tidskriftsartikel (refereegranskat)abstract Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
3.	2019 Tidskriftsartikel (refereegranskat)
4.	Dornelas, M., et al. (författare) BioTIME: A database of biodiversity time series for the Anthropocene 2018 Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 27:7, s. 760-786 Tidskriftsartikel (refereegranskat)abstract Motivation: The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene. Main types of variables included: The database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record. Spatial location and grain: BioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km(2) (158 cm(2)) to 100 km(2) (1,000,000,000,000 cm(2)). Time period and grainBio: TIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year. Major taxa and level of measurement: BioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates.
5.	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.
6.	Cossarizza, A., et al. (författare) Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition) 2019 Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973 Tidskriftsartikel (refereegranskat)abstract These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
7.	Vlasceanu, M, et al. (författare) Addressing climate change with behavioral science: A global intervention tournament in 63 countries 2024 Ingår i: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 10:6, s. eadj5778- Tidskriftsartikel (refereegranskat)
8.	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.
9.	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)
10.	Kato, Norihiro, et al. (författare) Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation 2015 Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293 Tidskriftsartikel (refereegranskat)abstract We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
11.	McHugh, DMS, et al. (författare) Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: a worldwide collaborative project 2011 Ingår i: Genetics in medicine : official journal of the American College of Medical Genetics. - 1530-0366. ; 13:3, s. 230-254 Tidskriftsartikel (refereegranskat)
12.	Richards, Stephen, et al. (författare) Genome Sequence of the Pea Aphid Acyrthosiphon pisum 2010 Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 8:2, s. e1000313- Tidskriftsartikel (refereegranskat)abstract Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems.
13.	Abrams, D, et al. (författare) Zidovudine, didanosine, and zalcitabine in the treatment of HIV infection: meta-analyses of the randomised evidence. HIV Trialists' Collaborative Group 1999 Ingår i: Lancet (London, England). - 0140-6736. ; 353:9169, s. 2014-2025 Tidskriftsartikel (refereegranskat)
14.	Geach, J.E., et al. (författare) The SCUBA-2 Cosmology Legacy Survey: 850 μm maps, catalogues and number counts 2017 Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 465:2, s. 1789-1806 Tidskriftsartikel (refereegranskat)abstract We present a catalogue of similar to 3000 submillimetre sources detected (>= 3.5 sigma) at 850 mu m over similar to 5 deg(2) surveyed as part of the James Clerk Maxwell Telescope (JCMT) SCUBA-2 Cosmology Legacy Survey (S2CLS). This is the largest survey of its kind at 850 mu m, increasing the sample size of 850 mu m selected submillimetre galaxies by an order of magnitude. The wide 850 mu m survey component of S2CLS covers the extragalactic fields: UKIDSS-UDS, COSMOS, Akari-NEP, Extended Groth Strip, Lockman Hole North, SSA22 and GOODS-North. The average 1s depth of S2CLS is 1.2 mJy beam(-1), approaching the SCUBA-2 850 mu m confusion limit, which we determine to be sigma(c) approximate to 0.8 mJy beam(-1). We measure the 850 mu m number counts, reducing the Poisson errors on the differential counts to approximately 4 per cent at S-850 approximate to 3 mJy. With several independent fields, we investigate field-to-field variance, finding that the number counts on 0.5 degrees-1 degrees scales are generally within 50 per cent of the S2CLS mean for S-850 > 3 mJy, with scatter consistent with the Poisson and estimated cosmic variance uncertainties, although there is a marginal (2 sigma) density enhancement in GOODS-North. The observed counts are in reasonable agreement with recent phenomenological and semi-analytic models, although determining the shape of the faint-end slope (S-850 < 3 mJy) remains a key test. The large solid angle of S2CLS allows us to measure the bright-end counts: at S-850 > 10 mJy there are approximately 10 sources per square degree, and we detect the distinctive up-turn in the number counts indicative of the detection of local sources of 850 mu m emission
15.	Mahmoodi, Bakhtawar K., et al. (författare) Association of Factor V Leiden With Subsequent Atherothrombotic Events A GENIUS-CHD Study of Individual Participant Data 2020 Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 142:6, s. 546-555 Tidskriftsartikel (refereegranskat)abstract Background: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD.Methods: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality.Results: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16];I-2=28%;P-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality were also close to identity.Conclusions: Factor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population.
16.	Patel, Riyaz S., et al. (författare) Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data 2019 Ingår i: Circulation. - 2574-8300. ; 12:4 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
17.	Patel, Riyaz S., et al. (författare) Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium 2019 Ingår i: Circulation. - 2574-8300. ; 12:4 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
18.	Sawcer, Stephen, et al. (författare) Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis 2011 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219 Tidskriftsartikel (refereegranskat)abstract Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
19.	Schunk, Stefan J., et al. (författare) Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality 2021 Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:18, s. 1742-1756 Tidskriftsartikel (refereegranskat)abstract AimsInflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1β can therapeutically be targeted. Associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown.Methods and resultsWe explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on the individual participant level in an explorative gene-centric approach without performing multiple testing. Functional relevance of single-nucleotide polymorphisms on NLRP3 inflammasome activation has been evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent (minor allele frequency 39.9%) intronic NLRP3 variant rs10754555 to affect NLRP3 gene expression. rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease was significantly higher as compared to non-carriers with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g. urate, triglycerides, apolipoprotein C3) modulated the association between rs10754555 and mortality.ConclusionThe NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent coronary artery disease, and mortality. This study provides evidence for a substantial role of genetically driven systemic inflammation in CVD and highlights the NLRP3 inflammasome as a therapeutic target.
20.	van Zuydam, Natalie R., et al. (författare) Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus 2020 Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 2574-8300. ; 13:6, s. 640-648 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D).METHODS: To test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D).RESULTS: None of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background.CONCLUSIONS: This study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.
21.	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. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120 Forskningsöversikt (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.
22.	Wilks, MF, et al. (författare) The European Registered Toxicologist (ERT): Current status and prospects for advancement 2016 Ingår i: Toxicology letters. - : Elsevier BV. - 1879-3169 .- 0378-4274. ; 259, s. 151-155 Tidskriftsartikel (refereegranskat)
23.	Bakx, Tom, 1990, et al. (författare) A dusty protocluster surrounding the binary galaxy HerBS-70 at z = 2.3 2024 Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 530:4, s. 4578-4596 Tidskriftsartikel (refereegranskat)abstract We report on deep SCUBA-2 observations at 850 μm and NOrthern Extended Millimetre Array (NOEMA) spectroscopic measurements at 2 mm of the environment surrounding the luminous, massive (M∗ ≈ 2 × 1011 M☉) Herschel-selected source HerBS-70. This source was revealed by previous NOEMA observations to be a binary system of dusty star-forming galaxies at z = 2.3, with the east component (HerBS-70E) hosting an active galactic nucleus. The SCUBA-2 observations detected, in addition to the binary system, 21 sources at >3.5σ over an area of ∼25 square comoving Mpc with a sensitivity of 1σ850 = 0.75 mJy. The surface density of continuum sources around HerBS-70 is three times higher than for field galaxies. The NOEMA spectroscopic measurements confirm the protocluster membership of three of the nine brightest sources through their CO(4–3) line emission, yielding a volume density 36 times higher than for field galaxies. All five confirmed sub-mm galaxies in the HerBS-70 system have relatively short gas depletion times (80−500 Myr), indicating the onset of quenching for this protocluster core due to the depletion of gas. The dark matter halo mass of the HerBS-70 system is estimated around 5 × 1013 M☉, with a projected current-day mass of 1015 M☉, similar to the local Virgo and Coma clusters. These observations support the claim that DSFGs, in particular the ones with observed multiplicity, can trace cosmic overdensities.
24.	Bendo, G. J., et al. (författare) The bright extragalactic ALMA redshift survey (BEARS) – II. Millimetre photometry of gravitational lens candidates 2023 Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 522:2, s. 2995-3017 Tidskriftsartikel (refereegranskat)abstract We present 101- and 151-GHz ALMA continuum images for 85 fields selected from Herschel observations that have 500-μm flux densities >80 mJy and 250–500-μm colours consistent with z > 2, most of which are expected to be gravitationally lensed or hyperluminous infrared galaxies. Approximately half of the Herschel 500-μm sources were resolved into multiple ALMA sources, but 11 of the 15 brightest 500-μm Herschel sources correspond to individual ALMA sources. For the 37 fields containing either a single source with a spectroscopic redshift or two sources with the same spectroscopic redshift, we examined the colour temperatures and dust emissivity indices. The colour temperatures only vary weakly with redshift and are statistically consistent with no redshift-dependent temperature variations, which generally corresponds to results from other samples selected in far-infrared, submillimetre, or millimetre bands but not to results from samples selected in optical or near-infrared bands. The dust emissivity indices, with very few exceptions, are largely consistent with a value of 2. We also compared spectroscopic redshifts to photometric redshifts based on spectral energy distribution templates designed for infrared-bright high-redshift galaxies. While the templates systematically underestimate the redshifts by ∼15 per cent, the inclusion of ALMA data decreases the scatter in the predicted redshifts by a factor of ∼2, illustrating the potential usefulness of these millimetre data for estimating photometric redshifts.
25.	Benson, Tyler W., et al. (författare) Gut Microbiota-Derived Trimethylamine N-Oxide Contributes to Abdominal Aortic Aneurysm Through Inflammatory and Apoptotic Mechanisms 2023 Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 147:14, s. 1079-1096 Tidskriftsartikel (refereegranskat)abstract Background:Large-scale human and mechanistic mouse studies indicate a strong relationship between the microbiome-dependent metabolite trimethylamine N-oxide (TMAO) and several cardiometabolic diseases. This study aims to investigate the role of TMAO in the pathogenesis of abdominal aortic aneurysm (AAA) and target its parent microbes as a potential pharmacological intervention.Methods:TMAO and choline metabolites were examined in plasma samples, with associated clinical data, from 2 independent patient cohorts (N=2129 total). Mice were fed a high-choline diet and underwent 2 murine AAA models, angiotensin II infusion in low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice or topical porcine pancreatic elastase in C57BL/6J mice. Gut microbial production of TMAO was inhibited through broad-spectrum antibiotics, targeted inhibition of the gut microbial choline TMA lyase (CutC/D) with fluoromethylcholine, or the use of mice genetically deficient in flavin monooxygenase 3 (Fmo3(-/-)). Finally, RNA sequencing of in vitro human vascular smooth muscle cells and in vivo mouse aortas was used to investigate how TMAO affects AAA.Results:Elevated TMAO was associated with increased AAA incidence and growth in both patient cohorts studied. Dietary choline supplementation augmented plasma TMAO and aortic diameter in both mouse models of AAA, which was suppressed with poorly absorbed oral broad-spectrum antibiotics. Treatment with fluoromethylcholine ablated TMAO production, attenuated choline-augmented aneurysm initiation, and halted progression of an established aneurysm model. In addition, Fmo3(-/-) mice had reduced plasma TMAO and aortic diameters and were protected from AAA rupture compared with wild-type mice. RNA sequencing and functional analyses revealed choline supplementation in mice or TMAO treatment of human vascular smooth muscle cells-augmented gene pathways associated with the endoplasmic reticulum stress response, specifically the endoplasmic reticulum stress kinase PERK.Conclusions:These results define a role for gut microbiota-generated TMAO in AAA formation through upregulation of endoplasmic reticulum stress-related pathways in the aortic wall. In addition, inhibition of microbiome-derived TMAO may serve as a novel therapeutic approach for AAA treatment where none currently exist.
26.	Berta, S., et al. (författare) z -GAL: A NOEMA spectroscopic redshift survey of bright Herschel galaxies: III. Physical properties 2023 Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 678 Tidskriftsartikel (refereegranskat)abstract The z-GAL survey observed 137 bright Herschel-selected targets with the IRAM Northern Extended Millimeter Array, with the aim to measure their redshift and study their properties. Several of them have been resolved into multiple sources. Consequently, robust spectroscopic redshifts have been measured for 165 individual galaxies in the range 0.8., <., z., <., 6.5. In this paper we analyse the millimetre spectra of the z-GAL sources, using both their continuum and line emission to derive their physical properties. At least two spectral lines are detected for each source, including transitions of 12CO, [CI], and H2O. The observed 12CO line ratios and spectral line energy distributions of individual sources resemble those of local starbursts. In seven sources the para-H2O (211-202) transition is detected and follows the IR versus H2O luminosity relation of sub-millimetre galaxies. The molecular gas mass of the z-GAL sources is derived from their 12CO, [CI], and sub-millimetre dust continuum emission. The three tracers lead to consistent results, with the dust continuum showing the largest scatter when compared to 12CO. The gas-to-dust mass ratio of these sources was computed by combining the information derived from 12CO and the dust continuum and has a median value of 107, similar to star-forming galaxies of near-solar metallicity. The same combined analysis leads to depletion timescales in the range between 0.1 and 1.0 Gyr, which place the z-GAL sources between the main sequence' of star formation and the locus of starbursts. Finally, we derived a first estimate of stellar masses "modulo possible gravitational magnification "by inverting known gas scaling relations: the z-GAL sample is confirmed to be mostly composed by starbursts, whereas ∼25% of its members lie on the main sequence of star-forming galaxies (within ±0.5 dex).
27.	Calkins, Hugh, et al. (författare) 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. 2018 Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 20:1, s. e1-e160 Tidskriftsartikel (refereegranskat)
28.	Corbett, Dale, et al. (författare) Enhancing the alignment of the preclinical and clinical stroke recovery research pipeline : Consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable translational working group 2017 Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949. ; 12:5, s. 462-471 Tidskriftsartikel (refereegranskat)abstract Stroke recovery research involves distinct biological and clinical targets compared to the study of acute stroke. Guidelines are proposed for the pre-clinical modeling of stroke recovery and for the alignment of pre-clinical studies to clinical trials in stroke recovery.
29.	Corbett, Dale, et al. (författare) Enhancing the Alignment of the Preclinical and Clinical Stroke Recovery Research Pipeline : Consensus-Based Core Recommendations from the Stroke Recovery and Rehabilitation Roundtable Translational Working Group ∗ 2017 Ingår i: Neurorehabilitation and Neural Repair. - : SAGE Publications. - 1545-9683 .- 1552-6844. ; 31:8, s. 699-707 Tidskriftsartikel (refereegranskat)abstract Stroke recovery research involves distinct biological and clinical targets compared to the study of acute stroke. Guidelines are proposed for the pre-clinical modeling of stroke recovery and for the alignment of pre-clinical studies to clinical trials in stroke recovery.
30.	Cox, P., et al. (författare) z-GAL: A NOEMA spectroscopic redshift survey of bright Herschel galaxies: I. Overview 2023 Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 678 Tidskriftsartikel (refereegranskat)abstract Using the IRAM NOrthern Extended Millimetre Array (NOEMA), we conducted a Large Programme (z-GAL) to measure redshifts for 126 bright galaxies detected in the Herschel Astrophysical Large Area Survey (H-ATLAS), the HerMES Large Mode Survey (HeLMS), and the Herschel Stripe 82 (HerS) Survey. We report reliable spectroscopic redshifts for a total of 124 of the Herschel-selected galaxies. The redshifts are estimated from scans of the 3 and 2-mm bands (and, for one source, the 1-mm band), covering up to 31 GHz in each band, and are based on the detection of at least two emission lines. Together with the Pilot Programme, where 11 sources had their spectroscopic redshifts measured, our survey has derived precise redshifts for 135 bright Herschel-selected galaxies, making it the largest sample of high-z galaxies with robust redshifts to date. Most emission lines detected are from 12CO (mainly from J = 2 1 to 5 4), with some sources seen in [CI] and H2O emission lines. The spectroscopic redshifts are in the range 0.8
31.	Crone, Elizabeth E., et al. (författare) Ability of Matrix Models to Explain the Past and Predict the Future of Plant Populations 2013 Ingår i: Conservation Biology. - : Wiley. - 0888-8892 .- 1523-1739. ; 27:5, s. 968-978 Tidskriftsartikel (refereegranskat)abstract Uncertainty associated with ecological forecasts has long been recognized, but forecast accuracy is rarely quantified. We evaluated how well data on 82 populations of 20 species of plants spanning 3 continents explained and predicted plant population dynamics. We parameterized stage-based matrix models with demographic data from individually marked plants and determined how well these models forecast population sizes observed at least 5 years into the future. Simple demographic models forecasted population dynamics poorly; only 40% of observed population sizes fell within our forecasts' 95% confidence limits. However, these models explained population dynamics during the years in which data were collected; observed changes in population size during the data-collection period were strongly positively correlated with population growth rate. Thus, these models are at least a sound way to quantify population status. Poor forecasts were not associated with the number of individual plants or years of data. We tested whether vital rates were density dependent and found both positive and negative density dependence. However, density dependence was not associated with forecast error. Forecast error was significantly associated with environmental differences between the data collection and forecast periods. To forecast population fates, more detailed models, such as those that project how environments are likely to change and how these changes will affect population dynamics, may be needed. Such detailed models are not always feasible. Thus, it may be wiser to make risk-averse decisions than to expect precise forecasts from models. Habilidad de los Modelos Matriciales para Explicar el Pasado y Predecir el Futuro de las Poblaciones de Plantas Resumen La incertidumbre asociada con el pronostico ecologico ha sido reconocida durante un largo tiempo pero rara vez se cuantifica su seguridad. Evaluamos que tan bien la informacion de 82 poblaciones de 20 especies de plantas a lo largo de 3 continentes explica y predice la dinamica de poblacion de las plantas. Realizamos parametros con modelos matriciales con base en estadios con datos demograficos a partir de plantas marcadas individualmente y determinamos que tan bien estos modelos pronostican el tamano de las poblaciones al menos 5 anos en el futuro. Los modelos demograficos simples pronosticaron pobremente las dinamicas de poblacion; solamente el 40% de las poblaciones observadas cayo dentro de los limites de confianza de 85% de nuestros pronosticos. Estos modelos sin embargo explicaron la dinamica de poblacion a lo largo de los anos en los que se colectaron datos; los cambios observados en el tamano de la poblacion durante el periodo de colecta de datos estuvieron positivamente correlacionados con la tasa de crecimiento de la poblacion. Asi, estos modelos son por lo menos una manera segura de cuantificar el estado de la poblacion. Los pronosticos debiles no estuvieron asociados con el numero de plantas individuales o con los anos de datos. Probamos si las tasas vitales dependian de la densidad y encontramos que existe dependencia hacia la densidad tanto positiva como negativa, sin embargo la dependencia de densidad no se asocio con el error de pronostico. El error de pronostico estuvo significativamente asociado con diferencias ambientales entre la recoleccion de datos y los periodos de pronostico. Para predecir el destino de las poblaciones se necesitan modelos mas detallados, como aquellos que proyectan los cambios probables en el ambiente y como estos cambios afectaran a la dinamica de las poblaciones. Tales modelos tan detallados no siempre son factibles. Por ello puede ser mejor tomar decisiones aversas a riesgos que esperar pronosticos precisos de los modelos.
32.	Crone, Elizabeth E., et al. (författare) How do plant ecologists use matrix population models? 2011 Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 14:1, s. 1-8 Tidskriftsartikel (refereegranskat)abstract P>Matrix projection models are among the most widely used tools in plant ecology. However, the way in which plant ecologists use and interpret these models differs from the way in which they are presented in the broader academic literature. In contrast to calls from earlier reviews, most studies of plant populations are based on < 5 matrices and present simple metrics such as deterministic population growth rates. However, plant ecologists also cautioned against literal interpretation of model predictions. Although academic studies have emphasized testing quantitative model predictions, such forecasts are not the way in which plant ecologists find matrix models to be most useful. Improving forecasting ability would necessitate increased model complexity and longer studies. Therefore, in addition to longer term studies with better links to environmental drivers, priorities for research include critically evaluating relative/comparative uses of matrix models and asking how we can use many short-term studies to understand long-term population dynamics.
33.	Dahlin, Joakim, et al. (författare) The Suspended Formalin Test : A Method Designed for Studying Formalin-Induced Behaviour in the Speke's Hingeback Tortoise (Kinixys spekii) 2012 Ingår i: Scandinavian Journal of Laboratory Animal Science. - 0901-3393. ; 39:1, s. 11-15 Tidskriftsartikel (refereegranskat)abstract The present study aimed to develop a method for testing pain-related behaviour induced by formalin in theSpeke’s hingeback tortoise (Kinixys spekii). These animals retract their head and limbs into their shell whenapproached, making behavioural testing almost impossible. It was found that suspending the animals in theair, facing away from the observer, made the animals keep their limbs out of the shell. Subcutaneous injectionof formalin induced easily identifiable and quantifiable behaviours that lasted for 20 minutes. Contraryto the biphasic effect of formalin observed in rats and mice, the response in tortoises was monophasic. Thesuspended formalin test may be useful for studying nociceptive mechanisms in tortoises, which in turn willbe important for a further understanding of the nociceptive system in reptiles as well as in mammals.
34.	de la Fuente, Eduardo, et al. (författare) Ultracompact H II regions with extended emission: the case of G43.89-0.78 and its molecular environment 2020 Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 497:4, s. 4436-4447 Tidskriftsartikel (refereegranskat)abstract The Karl Jansky Very Large Array (VLA), Owens Valley Radio Observatory (OVRO), Atacama Large Millimetric Array (ALMA), and the infrared Spitzer observatories are powerful facilities to study massive star formation regions and related objects such as ultra-compact (UC) H II regions, molecular clumps, and cores. We used these telescopes to study the UC H II region G43.89-0.78. The morphological study at arcminute scales using NVSS and Spitzer data shows that this region is similar to those observed in the bubble-like structures revealed by Spitzer observations. With this result, and including a physical characterization based on 3.6 cm data, we suggest G43.89-0.78 be classified as an UC H II region with Extended Emission because it meets the operational definition given in this paper comparing radio continuum data at 3.6 and 20 cm. For the ultra-compact component, we use VLA data to obtain physical parameters at 3.6 cm confirming this region as an UC H II region. Using ALMA observations, we detect the presence of a dense (2.6 x 10(7) cm(-3)) and small (similar to 2.0 arcsec; 0.08 pc) molecular clump with a mass of 220 M-circle dot and average kinetic temperature of 21 K, located near to the UC H II region. In this clump, catalogued as G43.890-0.784, water masers also exist, possibly tracing a bipolar outflow. We discover in this vicinity two additional clumps which we label as G43.899-0.786 (T-d = 50 K; M = 11 M-circle dot) and G43.888-0.787 (T-d = 50 K; M = 15 M-circle dot).
35.	Dirilgen, T., et al. (författare) Moving past neonicotinoids and honeybees : A systematic review of existing research on other insecticides and bees 2023 Ingår i: Environmental Research. - 0013-9351. ; 235 Forskningsöversikt (refereegranskat)abstract Synthetic pesticides (e.g. herbicides, fungicides and insecticides) are used widely in agriculture to protect crops from pests, weeds and disease. However, their use also comes with a range of environmental concerns. One key concern is the effect of insecticides on non-target organisms such as bees, who provide pollination services for crops and wild plants. This systematic literature review quantifies the existing research on bees and insecticides broadly, and then focuses more specifically on non-neonicotinoid insecticides and non-honeybees. We find that articles on honeybees (Apis sp.) and insecticides account for 80% of all research, with all other bees combined making up 20%. Neonicotinoids were studied in 34% of articles across all bees and were the most widely studied insecticide class for non-honeybees overall, with almost three times as many studies than the second most studied class. Of non-neonicotinoid insecticide classes and non-honeybees, the most studied were pyrethroids and organophosphates followed by carbamates, and the most widely represented bee taxa were bumblebees (Bombus), followed by leaf-cutter bees (Megachile) and mason bees (Osmia). Research has taken place across several countries, with the highest numbers of articles from Brazil and the US, and with notable gaps from countries in Asia, Africa and Oceania. Mortality was the most studied effect type, while sub-lethal effects such as on behaviour were less studied. Few studies tested how the effect of insecticides were influenced by multiple pressures, such as climate change and co-occurring pesticides (cocktail effects). As anthropogenic pressures do not occur in isolation, we suggest that future research also addresses these knowledge gaps. Given the changing global patterns in insecticide use, and the increasing inclusion of both non-honeybees and sub-lethal effects in pesticide risk assessment, there is a need for expanding research beyond its current state to ensure a strong scientific evidence base for the development of risk assessment and associated policy.
36.	Ercan, Ayse Bahar, et al. (författare) Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study. 2024 Ingår i: The Lancet Oncology. - 1470-2045. ; 25:5, s. 668-682 Tidskriftsartikel (refereegranskat)abstract Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD.In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries. Clinical data were extracted from the IRRDC database, medical records, and physician-completed case record forms. The primary objective was to describe the clinical features, cancer spectrum, and biology of the condition. Secondary objectives included estimations of cancer incidence and of the impact of the specific mismatch-repair gene and genotype on cancer onset and survival, including after cancer surveillance and immunotherapy interventions.We analysed data from 201 patients (103 males, 98 females) enrolled between June 5, 2007 and Sept 9, 2022. Median age at diagnosis of CMMRD or a related cancer was 8·9 years (IQR 5·9-12·6), and median follow-up from diagnosis was 7·2 years (3·6-14·8). Endogamy among minorities and closed communities contributed to high homozygosity within countries with low consanguinity. Frequent dermatological manifestations (117 [93%] of 126 patients with complete data) led to a clinical overlap with neurofibromatosis type 1 (35 [28%] of 126). 339 cancers were reported in 194 (97%) of 201 patients. The cumulative cancer incidence by age 18 years was 90% (95% CI 80-99). Median time between cancer diagnoses for patients with more than one cancer was 1·9 years (IQR 0·8-3·9). Neoplasms developed in 15 organs and included early-onset adult cancers. CNS tumours were the most frequent (173 [51%] cancers), followed by gastrointestinal (75 [22%]), haematological (61 [18%]), and other cancer types (30 [9%]). Patients with CNS tumours had the poorest overall survival rates (39% [95% CI 30-52] at 10 years from diagnosis; log-rank p<0·0001 across four cancer types), followed by those with haematological cancers (67% [55-82]), gastrointestinal cancers (89% [81-97]), and other solid tumours (96% [88-100]). All cancers showed high mutation and microsatellite indel burdens, and pathognomonic mutational signatures. MLH1 or MSH2 variants caused earlier cancer onset than PMS2 or MSH6 variants, and inferior survival (overall survival at age 15 years 63% [95% CI 55-73] for PMS2, 49% [35-68] for MSH6, 19% [6-66] for MLH1, and 0% for MSH2; p<0·0001). Frameshift or truncating variants within the same gene caused earlier cancers and inferior outcomes compared with missense variants (p<0·0001). The greater deleterious effects of MLH1 and MSH2 variants as compared with PMS2 and MSH6 variants persisted despite overall improvements in survival after surveillance or immune checkpoint inhibitor interventions.The very high cancer burden and unique genomic landscape of CMMRD highlight the benefit of comprehensive assays in timely diagnosis and precision approaches toward surveillance and immunotherapy. These data will guide the clinical management of children and patients who survive into adulthood with CMMRD.The Canadian Institutes for Health Research, Stand Up to Cancer, Children's Oncology Group National Cancer Institute Community Oncology Research Program, Canadian Cancer Society, Brain Canada, The V Foundation for Cancer Research, BioCanRx, Harry and Agnieszka Hall, Meagan's Walk, BRAINchild Canada, The LivWise Foundation, St Baldrick Foundation, Hold'em for Life, and Garron Family Cancer Center.
37.	Eriksson, Maria, et al. (författare) Insulin-Binding Peptide Probes Provide a Novel Strategy for Pancreatic β-Cell Imaging 2021 Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 18:12, s. 4428-4436 Tidskriftsartikel (refereegranskat)abstract Type 1 diabetes develops in childhood and adolescence, with peak incidence in the early teenage years. There is an urgent need for an accurate method to detect insulin-producing β-cells in patients that is not affected by alterations in β-cell function. As part of our research program to design specific probes to measure β-cell mass, we recently developed a novel insulin-binding peptide probe (IBPP) for the detection of β-cells in vivo. Here, we applied our innovative method to show specific labeling of this IBPP to human and mouse fixed β-cells in pancreatic islets. Importantly, we showed staining of human and mouse islets in culture without any negative functional or cell viability impact. Moreover, the IBPP-stained mouse islets after tail vein injection in vivo, albeit with batch differences in staining efficiency. In conclusion, we provide evidence showing that the IBPP can be used for future accurate detection of β-cell mass in a variety of preclinical models of diabetes.
38.	Estrader, M., et al. (författare) Robust antiferromagnetic coupling in hard-soft bi-magnetic core/shell nanoparticles 2013 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4 Tidskriftsartikel (refereegranskat)abstract The growing miniaturization demand of magnetic devices is fuelling the recent interest in bi-magnetic nanoparticles as ultimate small components. One of the main goals has been to reproduce practical magnetic properties observed so far in layered systems. In this context, although useful effects such as exchange bias or spring magnets have been demonstrated in core/shell nanoparticles, other interesting key properties for devices remain elusive. Here we show a robust antiferromagnetic (AFM) coupling in core/shell nanoparticles which, in turn, leads to the foremost elucidation of positive exchange bias in bi-magnetic hard-soft systems and the remarkable regulation of the resonance field and amplitude. The AFM coupling in iron oxide-manganese oxide based, soft/hard and hard/soft, core/shell nanoparticles is demonstrated by magnetometry, ferromagnetic resonance and X-ray magnetic circular dichroism. Monte Carlo simulations prove the consistency of the AFM coupling. This unique coupling could give rise to more advanced applications of bi-magnetic core/shell nanoparticles.
39.	Falstad, Niklas, 1987, et al. (författare) CON-quest: Searching for the most obscured galaxy nuclei 2021 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 649 Tidskriftsartikel (refereegranskat)abstract Context. Some luminous and ultraluminous infrared galaxies (LIRGs and ULIRGs) host extremely compact (r < 100 pc) and dusty nuclei. The high extinction associated with large column densities of gas and dust toward these objects render them hard to detect at many wavelengths. The intense infrared radiation arising from warm dust in these sources can provide a significant fraction of the bolometric luminosity of the galaxy and is prone to excite vibrational levels of molecules such as HCN. This results in emission from the rotational transitions of vibrationally excited HCN (HCN-vib); the brightest emission is found in compact obscured nuclei (CONs; ςHCN-vib > 1 L⊙ pc-2 in the J = 3-2 transition). However, there have been no systematic searches for CONs, and it is unknown how common they are. Aims. We aim to establish how common CONs are in the local Universe (z < 0.08), and whether their prevalence depends on the luminosity or other properties of the host galaxy. Methods. We conducted an Atacama Large Millimeter/submillimeter Array survey of the rotational J = 3-2 transition of HCN-vib in a volume-limited sample of 46 far-infrared luminous galaxies. Results. Compact obscured nuclei are identified in 38-13+18% of the ULIRGs, 21-6+12% of the LIRGs, and 0-0+9% of the lower luminosity galaxies. We find no dependence on the inclination of the host galaxy, but strong evidence of lower IRAS 25 μm to 60 μm flux density ratios (f25/f60) in CONs (with the exception of one galaxy, NGC 4418) compared to the rest of the sample. Furthermore, we find that CONs have stronger silicate features (s9.7 μm), but similar polycyclic aromatic hydrocarbon equivalent widths (EQW6.2 μm) compared to other galaxies. Along with signatures of molecular inflows seen in the far-infrared in most CONs, submillimeter observations also reveal compact, often collimated, outflows. Conclusions. In the local Universe, CONs are primarily found in (U)LIRGs, in which they are remarkably common. As such systems are often highly disturbed, inclinations are difficult to estimate, and high-resolution continuum observations of the individual nuclei are required to determine if the CON phenomenon is related to the inclinations of the nuclear disks. Further studies of the in- A nd outflow properties of CONs should also be conducted to investigate how these are connected to each other and to the CON phenomenon. The lower f25/f60 ratios in CONs as well as the results for the mid-infrared diagnostics investigated (EQW6.2 μm and s9.7 μm) are consistent with the notion that large dust columns gradually shift the radiation from the hot nucleus to longer wavelengths, making the mid- A nd far-infrared "photospheres"significantly cooler than the interior regions. Finally, to assess the importance of CONs in the context of galaxy evolution, it is necessary to extend this study to higher redshifts where (U)LIRGs are more common.
40.	Ginolfi, M., et al. (författare) Detection of companion galaxies around hot dust-obscured hyper-luminous galaxy W0410-0913 2022 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 13:1 Tidskriftsartikel (refereegranskat)abstract The phase transition between galaxies and quasars is often identified with the rare population of hyper-luminous, hot dust-obscured galaxies. Galaxy formation models predict these systems to grow via mergers, that can deliver large amounts of gas toward their centers, induce intense bursts of star formation and feed their supermassive black holes. Here we report the detection of 24 galaxies emitting Lyman-α emission on projected physical scales of about 400 kpc around the hyper-luminous hot dust-obscured galaxy W0410-0913, at redshift z = 3.631, using Very Large Telescope observations. While this indicates that W0410-0913 evolves in a very dense environment, we do not find clear signs of mergers that could sustain its growth. Data suggest that if mergers occurred, as models expect, these would involve less massive satellites, with only a moderate impact on the internal interstellar medium of W0410-0913, which is sustained by a rotationally-supported fast-rotating molecular disk, as Atacama Large Millimeter Array observations suggest.
41.	Gomez-Gener, L., et al. (författare) Global carbon dioxide efflux from rivers enhanced by high nocturnal emissions 2021 Ingår i: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 14, s. 289-294 Tidskriftsartikel (refereegranskat)abstract Carbon dioxide (CO2) emissions to the atmosphere from running waters are estimated to be four times greater than the total carbon (C) flux to the oceans. However, these fluxes remain poorly constrained because of substantial spatial and temporal variability in dissolved CO2 concentrations. Using a global compilation of high-frequency CO2 measurements, we demonstrate that nocturnal CO2 emissions are on average 27% (0.9 gC m(-2) d(-1)) greater than those estimated from diurnal concentrations alone. Constraints on light availability due to canopy shading or water colour are the principal controls on observed diel (24 hour) variation, suggesting this nocturnal increase arises from daytime fixation of CO2 by photosynthesis. Because current global estimates of CO2 emissions to the atmosphere from running waters (0.65-1.8 PgC yr(-1)) rely primarily on discrete measurements of dissolved CO2 obtained during the day, they substantially underestimate the magnitude of this flux. Accounting for night-time CO2 emissions may elevate global estimates from running waters to the atmosphere by 0.20-0.55 PgC yr(-1). Failing to account for emission differences between day and night will lead to an underestimate of global CO2 emissions from rivers by up to 0.55 PgC yr(-1), according to analyses of high-frequency CO2 measurements.
42.	Gorski, Mark, 1989, et al. (författare) A spectacular galactic scale magnetohydrodynamic powered wind in ESO 320-G030 2024 Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 684 Tidskriftsartikel (refereegranskat)abstract How galaxies regulate nuclear growth through gas accretion by supermassive black holes (SMBHs) is one of the most fundamental questions in galaxy evolution. One potential way to regulate nuclear growth is through a galactic wind that removes gas from the nucleus. It is unclear whether galactic winds are powered by jets, mechanical winds, radiation, or via magnetohydrodynamic (MHD) processes. Compact obscured nuclei represent a significant phase of galactic nuclear growth. These galaxies hide growing SMBHs or unusual starbursts in their very opaque, extremely compact (r < 100 pc) centres. They are found in approximately 30% of the luminous and ultra-luminous infrared galaxy population. Here, we present high-resolution ALMA observations (∼30 mas, ∼5 pc) of ground-state and vibrationally excited HCN towards ESO 320-G030 (IRAS 11506-3851). ESO 320-G030 is an isolated luminous infrared galaxy known to host a compact obscured nucleus and a kiloparsec-scale molecular wind. Our analysis of these high-resolution observations excludes the possibility of a starburst-driven wind, a mechanically or energy driven active galactic nucleus wind, and exposes a molecular MDH wind. These results imply that the nuclear evolution of galaxies and the growth of SMBHs are similar to the growth of hot cores or protostars where gravitational collapse of the nuclear torus drives a MHD wind. These results mean galaxies are capable, in part, of regulating the evolution of their nuclei without feedback.
43.	Hagimoto, Masato, et al. (författare) Bright extragalactic ALMA redshift survey (BEARS) III: detailed study of emission lines from 71 Herschel targets 2023 Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 521:4, s. 5508-5535 Tidskriftsartikel (refereegranskat)abstract We analyse the molecular and atomic emission lines of 71 bright Herschel-selected galaxies between redshifts 1.4 and 4.6 detected by the Atacama Large Millimeter/submillimeter Array. These lines include a total of 156 CO, [C i], and H2O emission lines. For 46 galaxies, we detect two transitions of CO lines, and for these galaxies we find gas properties similar to those of other dusty star-forming galaxy (DSFG) samples. A comparison to photodissociation models suggests that most of Herschel-selected galaxies have similar interstellar medium conditions as local infrared-luminous galaxies and high-redshift DSFGs, although with denser gas and more intense far-ultraviolet radiation fields than normal star-forming galaxies. The line luminosities agree with the luminosity scaling relations across five orders of magnitude, although the star formation and gas surface density distributions (i.e. Schmidt-Kennicutt relation) suggest a different star formation phase in our galaxies (and other DSFGs) compared to local and low-redshift gas-rich, normal star-forming systems. The gas-to-dust ratios of these galaxies are similar to Milky Way values, with no apparent redshift evolution. Four of 46 sources appear to have CO line ratios in excess of the expected maximum (thermalized) profile, suggesting a rare phase in the evolution of DSFGs. Finally, we create a deep stacked spectrum over a wide rest-frame frequency (220-890 GHz) that reveals faint transitions from HCN and CH, in line with previous stacking experiments.
44.	Hampton, Stephanie E., et al. (författare) Ecology under lake ice 2017 Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 20:1, s. 98-111 Forskningsöversikt (refereegranskat)abstract Winter conditions are rapidly changing in temperate ecosystems, particularly for those that experience periods of snow and ice cover. Relatively little is known of winter ecology in these systems, due to a historical research focus on summer ‘growing seasons’. We executed the first global quantitative synthesis on under-ice lake ecology, including 36 abiotic and biotic variables from 42 research groups and 101 lakes, examining seasonal differences and connections as well as how seasonal differences vary with geophysical factors. Plankton were more abundant under ice than expected; mean winter values were 43.2% of summer values for chlorophyll a, 15.8% of summer phytoplankton biovolume and 25.3% of summer zooplankton density. Dissolved nitrogen concentrations were typically higher during winter, and these differences were exaggerated in smaller lakes. Lake size also influenced winter-summer patterns for dissolved organic carbon (DOC), with higher winter DOC in smaller lakes. At coarse levels of taxonomic aggregation, phytoplankton and zooplankton community composition showed few systematic differences between seasons, although literature suggests that seasonal differences are frequently lake-specific, species-specific, or occur at the level of functional group. Within the subset of lakes that had longer time series, winter influenced the subsequent summer for some nutrient variables and zooplankton biomass.
45.	Huisman, Jaco, et al. (författare) Optimizing quality of information in Raw Material data collection across Europe. Recommendations for improving SRM datasets and harmonisation 2018 Rapport (övrigt vetenskapligt/konstnärligt)
46.	Ismail, D., et al. (författare) z-GAL: A NOEMA spectroscopic redshift survey of bright Herschel galaxies: II. Dust properties 2023 Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 678 Tidskriftsartikel (refereegranskat)abstract We present the dust properties of 125 bright Herschel galaxies selected from the z-GAL NOEMA spectroscopic redshift survey. All the galaxies have precise spectroscopic redshifts in the range 1.3 < z < 5.4. The large instantaneous bandwidth of NOEMA provides an exquisite sampling of the underlying dust continuum emission at 2 and 3 mm in the observed frame, with flux densities in at least four sidebands for each source. Together with the available Herschel 250, 350, and 500 μm and SCUBA-2 850 μm flux densities, the spectral energy distribution (SED) of each source can be analyzed from the far-infrared to the millimeter, with a fine sampling of the Rayleigh-Jeans tail. This wealth of data provides a solid basis to derive robust dust properties, in particular the dust emissivity index (β) and the dust temperature (Tdust). In order to demonstrate our ability to constrain the dust properties, we used a flux-generated mock catalog and analyzed the results under the assumption of an optically thin and optically thick modified black body emission. The robustness of the SED sampling for the z-GAL sources is highlighted by the mock analysis that showed high accuracy in estimating the continuum dust properties. These findings provided the basis for our detailed analysis of the z-GAL continuum data. We report a range of dust emissivities with β ∼1.5 -3 estimated up to high precision with relative uncertainties that vary in the range 7% 15%, and an average of 2.2 ± 0.3. We find dust temperatures varying from 20 to 50 K with an average of Tdust., ∼30 K for the optically thin case and Tdust., ∼38 K in the optically thick case. For all the sources, we estimate the dust masses and apparent infrared luminosities (based on the optically thin approach). An inverse correlation is found between Tdust and β with β Tdust-0.69, which is similar to what is seen in the local Universe. Finally, we report an increasing trend in the dust temperature as a function of redshift at a rate of 6.5 ±0.5 K/z for this 500 μm-selected sample. Based on this study, future prospects are outlined to further explore the evolution of dust temperature across cosmic time.
47.	Jallow, Muminatou, et al. (författare) Genome-wide and fine-resolution association analysis of malaria in West Africa. 2009 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; , s. 657-665 Tidskriftsartikel (refereegranskat)abstract We report a genome-wide association (GWA) study of severe malaria in The Gambia. The initial GWA scan included 2,500 children genotyped on the Affymetrix 500K GeneChip, and a replication study included 3,400 children. We used this to examine the performance of GWA methods in Africa. We found considerable population stratification, and also that signals of association at known malaria resistance loci were greatly attenuated owing to weak linkage disequilibrium (LD). To investigate possible solutions to the problem of low LD, we focused on the HbS locus, sequencing this region of the genome in 62 Gambian individuals and then using these data to conduct multipoint imputation in the GWA samples. This increased the signal of association, from P = 4 x 10(-7) to P = 4 x 10(-14), with the peak of the signal located precisely at the HbS causal variant. Our findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations.
48.	Kappos, Ludwig, et al. (författare) Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study 2018 Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 391, s. 1263-1273 Tidskriftsartikel (refereegranskat)abstract © 2018 Elsevier Ltd Background: No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS. Methods: This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatme nt arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings: 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Interpretation: Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Funding: Novartis Pharma AG.
49.	King, Siobhan M., et al. (författare) Iridium Nanoparticles for Multichannel Luminescence Lifetime Imaging, Mapping Localization in Live Cancer Cells 2018 Ingår i: Journal of the American Chemical Society. - 0002-7863 .- 1520-5126. ; 140, s. 10242-10249 Tidskriftsartikel (refereegranskat)abstract The development of long-lived luminescent nanoparticles for lifetime imaging is of wide interest as luminescence lifetime is environmentally sensitive detection independent of probe concentration. We report novel iridium-coated gold nanoparticles as probes for multiphoton lifetime imaging with characteristic long luminescent lifetimes based on iridium luminescence in the range of hundreds of nanoseconds and a short signal on the scale of picoseconds based on gold allowing multichannel detection. The tailor-made IrC6 complex forms stable, water-soluble gold nanoparticles (AuNPs) of 13, 25, and 100 nm, bearing 1400, 3200, and 22 000 IrC6 complexes per AuNP, respectively. The sensitivity of the iridium signal on the environment of the cell is evidenced with an observed variation of lifetimes. Clusters of iridium nanoparticles show lifetimes from 450 to 590 ns while lifetimes of 660 and 740 ns are an average of different points in the cytoplasm and nucleus. Independent luminescence lifetime studies of the nanoparticles in different media and under aggregation conditions postulate that the unusual long lifetimes observed can be attributed to interaction with proteins rather than nanoparticle aggregation. Total internal reflection fluorescence microscopy (TIRF), confocal microscopy studies and 3D luminescence lifetime stacks confirm the presence of bright, nonaggregated nanoparticles inside the cell. Inductively coupled plasma mass spectrometry (ICPMS) analysis further supports the presence of the nanoparticles in cells. The iridium-coated nanoparticles provide new nanoprobes for lifetime detection with dual channel monitoring. The combination of the sensitivity of the iridium signal to the cell environment together with the nanoscaffold to guide delivery offer opportunities for iridium nanoparticles for targeting and tracking in in vivo models.
50.	Kranendijk, Martijn, et al. (författare) IDH2 Mutations in Patients with D-2-Hydroxyglutaric Aciduria. 2010 Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 330:6002 Tidskriftsartikel (refereegranskat)abstract Heterozygous somatic mutations in the genes encoding isocitrate dehydrogenase- 1 and -2 (IDH1 and IDH2) were recently discovered in human neoplastic disorders. These mutations disable the enzymes' normal ability to convert isocitrate to 2-ketoglutarate (2-KG) and confer on the enzymes a new function: the ability to convert 2-KG to d-2-hydroxyglutarate (D-2-HG). We have detected heterozygous germline mutations in IDH2 that alter enzyme residue R140 in 15 unrelated patients with d-2-hydroxyglutaric aciduria (D-2-HGA), a rare neurometabolic disorder characterized by supraphysiological levels of D-2-HG. These findings provide additional impetus for investigating the role of D-2-HG in the pathophysiology of metabolic disease and cancer.

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