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2.
  • Munk, P., et al. (författare)
  • Genomic analysis of sewage from 101 countries reveals global landscape of antimicrobial resistance
  • 2022
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Antimicrobial resistance (AMR) is a major threat to global health. Understanding the emergence, evolution, and transmission of individual antibiotic resistance genes (ARGs) is essential to develop sustainable strategies combatting this threat. Here, we use metagenomic sequencing to analyse ARGs in 757 sewage samples from 243 cities in 101 countries, collected from 2016 to 2019. We find regional patterns in resistomes, and these differ between subsets corresponding to drug classes and are partly driven by taxonomic variation. The genetic environments of 49 common ARGs are highly diverse, with most common ARGs carried by multiple distinct genomic contexts globally and sometimes on plasmids. Analysis of flanking sequence revealed ARG-specific patterns of dispersal limitation and global transmission. Our data furthermore suggest certain geographies are more prone to transmission events and should receive additional attention.
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3.
  • Abe, O, et al. (författare)
  • Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
  • 2005
  • Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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4.
  • Thompson, B.A., et al. (författare)
  • Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database
  • 2014
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:2, s. 107-115
  • Tidskriftsartikel (refereegranskat)abstract
    • The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and apply a standardized classification scheme to constitutional variants in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2. Unpublished data submission was encouraged to assist in variant classification and was recognized through microattribution. The scheme was refined by multidisciplinary expert committee review of the clinical and functional data available for variants, applied to 2,360 sequence alterations, and disseminated online. Assessment using validated criteria altered classifications for 66% of 12,006 database entries. Clinical recommendations based on transparent evaluation are now possible for 1,370 variants that were not obviously protein truncating from nomenclature. This large-scale endeavor will facilitate the consistent management of families suspected to have Lynch syndrome and demonstrates the value of multidisciplinary collaboration in the curation and classification of variants in public locus-specific databases. © 2014 Nature America, Inc.
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5.
  • Bentham, James, et al. (författare)
  • A century of trends in adult human height
  • 2016
  • Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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6.
  • Beral, V, et al. (författare)
  • Alcohol, tobacco and breast cancer - collaborative reanalysis of individual data from 53 epidemiological studies, including 58515 women with breast cancer and 95067 women without the disease
  • 2002
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 87, s. 1234-45
  • Tidskriftsartikel (refereegranskat)abstract
    • Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58515 women with invasive breast cancer and 95067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19 - 1.45, P < 0.00001) for an intake of 35 - 44 g per day alcohol, and 1.46 (1.33 - 1.61, P < 0.00001) for greater than or equal to 45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1 % per 10 g per day, P < 0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers= 1.03, 95% CI 0.98 - 1.07, and for current smokers=0.99, 0.92 - 1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver. (C) 2002 Cancer Research UK.
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9.
  • Lagrange, A. -M., et al. (författare)
  • Post-conjunction detection of beta Pictoris b with VLT/SPHERE
  • 2019
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 621
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. With an orbital distance comparable to that of Saturn in the solar system, beta Pictoris b is the closest (semi-major axis similar or equal to 9 au) exoplanet that has been imaged to orbit a star. Thus it offers unique opportunities for detailed studies of its orbital, physical, and atmospheric properties, and of disk-planet interactions. With the exception of the discovery observations in 2003 with NaCo at the Very Large Telescope (VLT), all following astrometric measurements relative to beta Pictoris have been obtained in the southwestern part of the orbit, which severely limits the determination of the planet's orbital parameters.Aims. We aimed at further constraining beta Pictoris b orbital properties using more data, and, in particular, data taken in the northeastern part of the orbit.Methods. We used SPHERE at the VLT to precisely monitor the orbital motion of beta beta Pictoris b since first light of the instrument in 2014.Results. We were able to monitor the planet until November 2016, when its angular separation became too small (125 mas, i.e., 1.6 au) and prevented further detection. We redetected beta Pictoris b on the northeast side of the disk at a separation of 139 mas and a PA of 30 degrees in September 2018. The planetary orbit is now well constrained. With a semi-major axis (sma) of a = 9.0 +/- 0.5 au (1 sigma), it definitely excludes previously reported possible long orbital periods, and excludes beta Pictoris b as the origin of photometric variations that took place in 1981. We also refine the eccentricity and inclination of the planet. From an instrumental point of view, these data demonstrate that it is possible to detect, if they exist, young massive Jupiters that orbit at less than 2 au from a star that is 20 pc away.
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10.
  • Zhou, Bin, et al. (författare)
  • Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants
  • 2016
  • Ingår i: The Lancet. - : Elsevier B.V.. - 0140-6736 .- 1474-547X. ; 387:10027, s. 1513-1530
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are aff ecting the number of adults with diabetes.Methods: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue.Findings: We used data from 751 studies including 4372000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-17.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target.Interpretation: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults aff ected, has increased faster in low-income and middle-income countries than in high-income countries.
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11.
  • Choularton, T. W., et al. (författare)
  • The Great Dun Fell Cloud Experiment 1993 : An overview
  • 1997
  • Ingår i: Atmospheric Environment. - 1352-2310. ; 31:16, s. 2393-2405
  • Tidskriftsartikel (refereegranskat)abstract
    • The 1993 Ground-based Cloud Experiment on Great Dun Fell used a wide range of measurements of trace gases, aerosol particles and cloud droplets at five sites to study their sources and sinks especially those in cloud. These measurements have been interpreted using a variety of models. The conclusions add to our knowledge of air pollution, acidification of the atmosphere and the ground, eutrophication and climate change. The experiment is designed to use the hill cap cloud as a flow-through reactor, and was conducted in varying levels of pollution typical of much of the rural temperate continental northern hemisphere in spring-time.
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12.
  • Lederman, J. S., et al. (författare)
  • International collaborative follow-up investigation of graduating high school students' understandings of the nature of scientific inquiry : is progress Being made?
  • 2021
  • Ingår i: International Journal of Science Education. - : Informa UK Limited. - 0950-0693 .- 1464-5289. ; 43:7, s. 991-1016
  • Tidskriftsartikel (refereegranskat)abstract
    • Understandings of the nature of scientific inquiry (NOSI), as opposed to engaging students in inquiry learning experiences, are included in science education reform documents around the world. However, little is known about what students have learned about NOSI during their pre-college school years. The purpose of this large-scale follow-up international project (i.e. 32 countries and regions, spanning six continents and including 3917 students for the high school sample) was to collect data on what exiting high school students have learned about NOSI. Additionally, the study investigated changes in 12th grade students' NOSI understandings compared to seventh grade (i.e. 20 countries and regions) students' understandings from a prior investigation [Lederman et al. (2019). An international collaborative investigation of beginning seventh grade students' understandings of scientific inquiry: Establishing a baseline. Journal of Research in Science Teaching, 56(4), 486-515. ]. This study documents and discusses graduating high school students' understandings and compares their understandings to seventh grade students' understandings of the same aspects of scientific inquiry for each country. It is important to note that collecting data from each of the 130+ countries globally was not feasible. Similarly, it was not possible to collect data from every region of each country. A concerted effort was made, however, to provide a relatively representative picture of each country and the world.
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13.
  • Anderson, J. P., et al. (författare)
  • A nearby super-luminous supernova with a long pre-maximum plateau and strong C (II) features
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 620
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Super-luminous supernovae (SLSNe) are rare events defined as being significantly more luminous than normal terminal stellar explosions. The source of the additional power needed to achieve such luminosities is still unclear. Discoveries in the local Universe (i.e. z < 0.1) are scarce, but afford dense multi-wavelength observations. Additional low-redshift objects are therefore extremely valuable.Aims. We present early-time observations of the type I SLSN ASASSN-18km/SN 2018bsz. These data are used to characterise the event and compare to literature SLSNe and spectral models. Host galaxy properties are also analysed.Methods. Optical and near-IR photometry and spectroscopy were analysed. Early-time ATLAS photometry was used to constrain the rising light curve. We identified a number of spectral features in optical-wavelength spectra and track their time evolution. Finally, we used archival host galaxy photometry together with H( II )region spectra to constrain the host environment.Results. ASASSN-18km/SN 2018bsz is found to be a type I SLSN in a galaxy at a redshift of 0.0267 (111 Mpc), making it the lowest-redshift event discovered to date. Strong C- II lines are identified in the spectra. Spectral models produced by exploding a Wolf-Rayet progenitor and injecting a magnetar power source are shown to be qualitatively similar to ASASSN-18km/SN 2018bsz, contrary to most SLSNe-I that display weak or non-existent C (II) lines. ASASSN-18km/SN 2018bsz displays along, slowly rising, red plateau of >26 days, before a steeper, faster rise to maximum. The host has an absolute magnitude of -19.8 mag (r), a mass of M-* = 1.5(-0.33)(+0.08) x 10(9) M-circle dot, and a star formation rate of =0.50(-0.19)(+2.22) M-circle dot yr(-1). A nearby H (II) region has an oxygen abundance (O3N2) of 8.31 +/- 0.01 dex.
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14.
  • Astuto, L. M., et al. (författare)
  • CDH23 mutation and phenotype heterogeneity : a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness
  • 2002
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 71:2, s. 262-275
  • Tidskriftsartikel (refereegranskat)abstract
    • Usher syndrome type I is characterized by congenital hearing loss, retinitis pigmentosa (RP), and variable vestibular areflexia. Usher syndrome type ID, one of seven Usher syndrome type I genetic localizations, have been mapped to a chromosomal interval that overlaps with a nonsyndromic-deafness localization, DFNB12. Mutations in CDH23, a gene that encodes a putative cell-adhesion protein with multiple cadherin-like domains, are responsible for both Usher syndrome and DFNB12 nonsyndromic deafness. Specific CDH23 mutational defects have been identified that differentiate these two phenotypes. Only missense mutations of CDH23 have been observed in families with nonsyndromic deafness, whereas nonsense, frameshift, splice-site, and missense mutations have been identified in families with Usher syndrome. In the present study, a panel of 69 probands with Usher syndrome and 38 probands with recessive nonsyndromic deafness were screened for the presence of mutations in the entire coding region of CDH23, by heteroduplex, single-strand conformation polymorphism, and direct sequence analyses. A total of 36 different CDH23 mutations were detected in 45 families; 33 of these mutations were novel, including 18 missense, 3 nonsense, 5 splicing defects, 5 microdeletions, and 2 insertions. A total of seven mutations were common to more than one family. Numerous exonic and intronic polymorphisms also were detected. Results of ophthalmologic examinations of the patients with nonsyndromic deafness have found asymptomatic RP-like manifestations, indicating that missense mutations may have a subtle effect in the retina. Furthermore, patients with mutations in CDH23 display a wide range of hearing loss and RP phenotypes, differing in severity, age at onset, type, and the presence or absence of vestibular areflexia.
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16.
  • Grahn, T., et al. (författare)
  • Collectivity and configuration mixing in Pb186,188 and Po194
  • 2006
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 97:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Lifetimes of prolate intruder states in Pb186 and oblate intruder states in Po194 have been determined by employing, for the first time, the recoil-decay tagging technique in recoil distance Doppler-shift lifetime measurements. In addition, lifetime measurements of prolate states in Pb188 up to the 8+ state were carried out using the recoil-gating method. The B(E2) values have been deduced from which deformation parameters |β2|=0.29(5) and |β2|=0.17(3) for the prolate and the oblate bands, respectively, have been extracted. The results also shed new light on the mixing between different shapes.
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17.
  • Haas, SS, et al. (författare)
  • Normative modeling of brain morphometry in Clinical High-Risk for Psychosis
  • 2023
  • Ingår i: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • ImportanceThe lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in the majority of individuals at psychosis risk may be nested within the range observed in healthy individuals.ObjectiveTo quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high-risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder.Design, Setting, and ParticipantsClinical, IQ and FreeSurfer-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1,340 CHR-P individuals [47.09% female; mean age: 20.75 (4.74) years] and 1,237 healthy individuals [44.70% female; mean age: 22.32 (4.95) years] from 29 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group.Main Outcomes and MeasuresFor each regional morphometric measure, z-scores were computed that index the degree of deviation from the normative means of that measure in a healthy reference population (N=37,407). Average deviation scores (ADS) for CT, SA, SV, and globally across all measures (G) were generated by averaging the respective regional z-scores. Regression analyses were used to quantify the association of deviation scores with clinical severity and cognition and two-proportion z-tests to identify case-control differences in the proportion of individuals with infranormal (z<-1.96) or supranormal (z>1.96) scores.ResultsCHR-P and healthy individuals overlapped in the distributions of the observed values, regional z-scores, and all ADS vales. The proportion of CHR-P individuals with infranormal or supranormal values in any metric was low (<12%) and similar to that of healthy individuals. CHR-P individuals who converted to psychosis compared to those who did not convert had a higher percentage of infranormal values in temporal regions (5-7% vs 0.9-1.4%). In the CHR-P group, only the ADSSAshowed significant but weak associations (|β|<0.09; PFDR<0.05) with positive symptoms and IQ.Conclusions and RelevanceThe study findings challenge the usefulness of macroscale neuromorphometric measures as diagnostic biomarkers of psychosis risk and suggest that such measures do not provide an adequate explanation for psychosis risk.Key pointsQuestionIs the risk of psychosis associated with brain morphometric changes that deviate significantly from healthy variation?FindingsIn this study of 1340 individuals high-risk for psychosis (CHR-P) and 1237 healthy participants, individual-level variation in macroscale neuromorphometric measures of the CHR-P group was largely nested within healthy variation and was not associated with the severity of positive psychotic symptoms or conversion to a psychotic disorder.MeaningThe findings suggest the macroscale neuromorphometric measures have limited utility as diagnostic biomarkers of psychosis risk.
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18.
  • Horikoshi, Momoko, et al. (författare)
  • New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
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19.
  • Kuschmierz, Paul, et al. (författare)
  • European first-year university students accept evolution but lack substantial knowledge about it : A standardized European cross-country assessment
  • 2021
  • Ingår i: Evolution. - : BioMed Central (BMC). - 1936-6426 .- 1936-6434. ; 14:1, s. 1-22
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Investigations of evolution knowledge and acceptance and their relation are central to evolution education research. Ambiguous results in this field of study demonstrate a variety of measuring issues, for instance differently theorized constructs, or a lack of standardized methods, especially for cross-country comparisons. In particular, meaningful comparisons across European countries, with their varying cultural backgrounds and education systems, are rare, often include only few countries, and lack standardization. To address these deficits, we conducted a standardized European survey, on 9200 first-year university students in 26 European countries utilizing a validated, comprehensive questionnaire, the “Evolution Education Questionnaire”, to assess evolution acceptance and knowledge, as well as influencing factors on evolution acceptance. Results: We found that, despite European countries’ different cultural backgrounds and education systems, European first-year university students generally accept evolution. At the same time, they lack substantial knowledge about it, even if they are enrolled in a biology-related study program. Additionally, we developed a multilevel-model that determines religious faith as the main influencing factor in accepting evolution. According to our model, knowledge about evolution and interest in biological topics also increase acceptance of evolution, but to a much lesser extent than religious faith. The effect of age and sex, as well as the country’s affiliation, students’ denomination, and whether or not a student is enrolled in a biology-related university program, is negligible. Conclusions: Our findings indicate that, despite all their differences, most of the European education systems for upper secondary education lead to acceptance of evolution at least in university students. It appears that, at least in this sample, the differences in knowledge between countries reflect neither the extent to which school curricula cover evolutionary biology nor the percentage of biology-related students in the country samples. Future studies should investigate the role of different European school curricula, identify particularly problematic or underrepresented evolutionary concepts in biology education, and analyze the role of religious faith when teaching evolution.
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20.
  • Moschner, K., et al. (författare)
  • Relativistic Coulomb excitation of 88Kr
  • 2016
  • Ingår i: Physical Review C - Nuclear Physics. - 0556-2813. ; 94:5
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate the systematics of mixed-symmetry states in N=52 isotones, a relativistic Coulomb excitation experiment was performed during the PreSPEC campaign at the GSI Helmholtzzentrum für Schwerionenforschung to determine E2 transition strengths to 2+ states of the radioactive nucleus 88Kr. Absolute transition rates could be measured towards the first and third 2+ states. For the latter a mixed-symmetry character is suggested on the basis of the indication for a strong M1 transition to the fully symmetric 2+1 state, extending the knowledge of the N=52 isotones below Z=40. A comparison with the proton-neutron interacting boson model and shell-model predictions is made and supports the assignment.
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21.
  • Muro-Arena, G. A., et al. (författare)
  • Spirals inside the millimeter cavity of transition disk SR 21
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 636
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Hydrodynamical simulations of planet-disk interactions suggest that planets may be responsible for a number of the substructures frequently observed in disks in both scattered light and dust thermal emission. Despite the ubiquity of these features, direct evidence of planets embedded in disks and of the specific interaction features like spiral arms within planetary gaps are still rare.Aims. In this study we discuss recent observational results in the context of hydrodynamical simulations in order to infer the properties of a putative embedded planet in the cavity of a transition disk.Methods. We imaged the transition disk SR 21 in H-band in scattered light with SPHERE/IRDIS and in thermal dust emission with ALMA band 3 (3 mm) observations at a spatial resolution of 0.1 ''. We combine these datasets with existing Band 9 (430 mu m) and Band 7 (870 mu m) ALMA continuum data.Results. The Band 3 continuum data reveals a large cavity and a bright ring peaking at 53 au strongly suggestive of dust trapping. The ring shows a pronounced azimuthal asymmetry, with a bright region in the northwest that we interpret as a dust overdensity. A similarly asymmetric ring is revealed at the same location in polarized scattered light, in addition to a set of bright spirals inside the millimeter cavity and a fainter spiral bridging the gap to the outer ring. These features are consistent with a number of previous hydrodynamical models of planet-disk interactions, and suggest the presence of a similar to 1 M-Jup planet at 44 au and PA = 11 deg. This makes SR21 the first disk showing spiral arms inside the millimeter cavity, and the first disk for which the location of a putative planet can be precisely inferred.Conclusions. The main features of SR 21 in both scattered light and thermal emission are consistent with hydrodynamical predictions of planet-disk interactions. With the location of a possible planet being well constrained by observations, it is an ideal candidate for follow-up observations to search for direct evidence of a planetary companion still embedded in its disk.
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22.
  • Sztuk-Dambietz, J., et al. (författare)
  • Operational experience with Adaptive Gain Integrating Pixel Detectors at European XFEL
  • 2024
  • Ingår i: Frontiers in Physics. - : Frontiers Media SA. - 2296-424X. ; 11
  • Forskningsöversikt (refereegranskat)abstract
    • The European X-ray Free Electron Laser (European XFEL) is a cutting-edge user facility that generates per second up to 27,000 ultra-short, spatially coherent X-ray pulses within an energy range of 0.26 to more than 20 keV. Specialized instrumentation, including various 2D X-ray detectors capable of handling the unique time structure of the beam, is required. The one-megapixel AGIPD (AGIPD1M) detectors, developed for the European XFEL by the AGIPD Consortium, are the primary detectors used for user experiments at the SPB/SFX and MID instruments. The first AGIPD1M detector was installed at SPB/SFX when the facility began operation in 2017, and the second one was installed at MID in November 2018. The AGIPD detector systems require a dedicated infrastructure, well-defined safety systems, and high-level control procedures to ensure stable and safe operation. As of now, the AGIPD1M detectors installed at the SPB/SFX and MID experimental end stations are fully integrated into the European XFEL environment, including mechanical integration, vacuum, power, control, data acquisition, and data processing systems. Specific high-level procedures allow facilitated detector control, and dedicated interlock systems based on Programmable Logic Controllers ensure detector safety in case of power, vacuum, or cooling failure. The first 6 years of operation have clearly demonstrated that the AGIPD1M detectors provide high-quality scientific results. The collected data, along with additional dedicated studies, have also enabled the identification and quantification of issues related to detector performance, ensuring stable operation. Characterization and calibration of detectors are among the most critical and challenging aspects of operation due to their complex nature. A methodology has been developed to enable detector characterization and data correction, both in near real-time (online) and offline mode. The calibration process optimizes detector performance and ensures the highest quality of experimental results. Overall, the experience gained from integrating and operating the AGIPD detectors at the European XFEL, along with the developed methodology for detector characterization and calibration, provides valuable insights for the development of next-generation detectors for Free Electron Laser X-ray sources. 
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23.
  • Willerslev, E, et al. (författare)
  • Fifty thousand years of arctic vegetation change and megafauna diet
  • 2014
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 506:7486, s. 47-47
  • Tidskriftsartikel (refereegranskat)abstract
    • Although it is generally agreed that the Arctic flora is among the youngest and least diverse on Earth, the processes that shaped it are poorly understood. Here we present 50 thousand years (kyr) of Arctic vegetation history, derived from the first large-scale ancient DNA metabarcoding study of circumpolar plant diversity. For this interval we also explore nematode diversity as a proxy for modelling vegetation cover and soil quality, and diets of herbivorous megafaunal mammals, many of which became extinct around 10 kyr bp (before present). For much of the period investigated, Arctic vegetation consisted of dry steppe-tundra dominated by forbs (non-graminoid herbaceous vascular plants). During the Last Glacial Maximum (25–15 kyr bp), diversity declined markedly, although forbs remained dominant. Much changed after 10 kyr bp, with the appearance of moist tundra dominated by woody plants and graminoids. Our analyses indicate that both graminoids and forbs would have featured in megafaunal diets. As such, our findings question the predominance of a Late Quaternary graminoid-dominated Arctic mammoth steppe.
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24.
  • Arnold, L.J., et al. (författare)
  • Paper II - Dirt, dates and DNA: OSL and radiocarbon chronologies of perennially-frozen sediments in Siberia, and their implications for sedimentary ancient DNA studies
  • 2011
  • Ingår i: Boreas. - : Wiley. - 1502-3885 .- 0300-9483. ; 40:3, s. 417-445
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract in UndeterminedThe sedimentary ancient DNA (sedaDNA) technique offers a potentially invaluable means of investigating species evolution and extinction dynamics in high-latitude environments. An implicit assumption of the sedaDNA approach is that the extracted DNA is autochthonous with the host deposit and that it has not been physically transported from older source deposits or reworked within the sedimentary profile by postdepositional mixing. In this paper we investigate whether these fundamental conditions are upheld at seven perennially frozen wetland sites across the Taimyr Peninsula and coastal lowlands of north-central Siberia. Optically stimulated luminescence (OSL) and radiocarbon (C-14) dating are used to constrain the ages of both the inorganic and organic fractions of perennially frozen deposits from which sedaDNA of extinct and extant species have been recovered. OSL and C-14 age/depth profiles, as well as single-grain equivalent dose (De) distribution characteristics, are used to assess the stratigraphic integrity of these sedaDNA sequences by (i) identifying the presence of primary or reworked organic and inorganic material, and (ii) examining the types of depositional and postdepositional processes that have affected specific sedimentary facies. The results of this study demonstrate that even though DNA preservation and stratigraphic integrity are commonly superior in perennially frozen settings, this does not, in itself, guarantee the suitability of the sedaDNA approach. The combined OSL and C-14 chronologies reveal that certain perennially frozen sites may be poorly suited for sedaDNA analysis, and that careful site selection is paramount to ensuring the accuracy of any sedaDNA study - particularly for 'latest appearance date' estimates of extinct taxa.
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25.
  • Baron, P., et al. (författare)
  • The level 2 research product algorithms for the superconducting submillimeter-wave limb-emission sounder (SMILES)
  • 2011
  • Ingår i: Atmospheric Measurement Techniques Discussions. - : Copernicus GmbH. - 1867-8610. ; 4:3, s. 3593-3645
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper describes the algorithms of the level-2 research (L2r) processingchain developed for the Superconducting Submillimeter-Wave Limb-EmissionSounder (SMILES). The chain has been developed in parallel to the operationalchain for conducting researches on calibration and retrieval algorithms. L2rchain products are available to the scientific community. The objective ofversion 2 is the retrieval of the vertical distribution of trace gases in thealtitude range of 18-90 km. An theoretical error analysis is conducted toestimate the retrieval feasibility of key parameters of the processing:line-of-sight elevation tangent altitudes (or angles), temperature and O3 profiles. The line-of-sight tangent altitudes are retrievedbetween 20 and 50 km from the strong ozone (O3) line at 625.371 GHz,with low correlation with the O3 volume-mixing ratio and temperatureretrieved profiles. Neglecting the non-linearity of the radiometric gain inthe calibration procedure is the main systematic error. It is large for theretrieved temperature (between 5-10 K). Therefore, atmospheric pressure cannot be derived from the retrieved temperature, and, then, in the altituderange where the line-of-sight tangent altitudes are retrieved, the retrievedtrace gases profiles are found to be better represented on pressure levelsthan on altitude levels. The error analysis for the retrieved HOCl profiledemonstrates that best results for inverting weak lines can be obtained byusing narrow spectral windows. Future versions of the L2r algorithms willimprove the temperature/pressure retrievals and also provide information inthe upper tropospheric/lower stratospheric region (e.g., water vapor, icecontent, O3) and on stratospheric and mesospheric line-of-sight winds.
  •  
26.
  • Baron, P., et al. (författare)
  • The Level 2 research product algorithms for the Superconducting Submillimeter-Wave Limb-Emission Sounder (SMILES)
  • 2011
  • Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 4, s. 2105-2124
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper describes the algorithms of the level-2 research (L2r) processing chain developed for the Superconducting Submillimeter-Wave Limb-Emission Sounder (SMILES). The chain has been developed in parallel to the operational chain for conducting researches on calibration and retrieval algorithms. L2r chain products are available to the scientific community. The objective of version 2 is the retrieval of the vertical distribution of trace gases in the altitude range of 18–90 km. A theoretical error analysis is conducted to estimate the retrieval feasibility of key parameters of the processing: line-of-sight elevation tangent altitudes (or angles), temperature and ozone profiles. While pointing information is often retrieved from molecular oxygen lines, there is no oxygen line in the SMILES spectra, so the strong ozone line at 625.371 GHz has been chosen. The pointing parameters and the ozone profiles are retrieved from the line wings which are measured with high signal to noise ratio, whereas the temperature profile is retrieved from the optically thick line center. The main systematic component of the retrieval error was found to be the neglect of the non-linearity of the radiometric gain in the calibration procedure. This causes a temperature retrieval error of 5–10 K. Because of these large temperature errors, it is not possible to construct a reliable hydrostatic pressure profile. However, as a consequence of the retrieval of pointing parameters, pressure induced errors are significantly reduced if the retrieved trace gas profiles are represented on pressure levels instead of geometric altitude levels. Further, various setups of trace gas retrievals have been tested. The error analysis for the retrieved HOCl profile demonstrates that best results for inverting weak lines can be obtained by using narrow spectral windows.
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27.
  • Bensi, M., et al. (författare)
  • Deep flow variability offshore south-west Svalbard (fram strait)
  • 2019
  • Ingår i: Water. - : MDPI AG. - 2073-4441. ; 11:4
  • Tidskriftsartikel (refereegranskat)abstract
    • - Water mass generation and mixing in the eastern Fram Strait are strongly influenced by the interaction between Atlantic and Arctic waters and by the local atmospheric forcing, which produce dense water that substantially contributes to maintaining the global thermohaline circulation. The West Spitsbergen margin is an ideal area to study such processes. Hence, in order to investigate the deep flow variability on short-term, seasonal, and multiannual timescales, two moorings were deployed at ~1040 m depth on the southwest Spitsbergen continental slope. We present and discuss time series data collected between June 2014 and June 2016. They reveal thermohaline and current fluctuations that were largest from October to April, when the deep layer, typically occupied by Norwegian Sea Deep Water, was perturbed by sporadic intrusions of warmer, saltier, and less dense water. Surprisingly, the observed anomalies occurred quasi-simultaneously at both sites, despite their distance (~170 km). We argue that these anomalies may arise mainly by the effect of topographically trapped waves excited and modulated by atmospheric forcing. Propagation of internal waves causes a change in the vertical distribution of the Atlantic water, which can reach deep layers. During such events, strong currents typically precede thermohaline variations without significant changes in turbidity. However, turbidity increases during April-June in concomitance with enhanced downslope currents. Since prolonged injections of warm water within the deep layer could lead to a progressive reduction of the density of the abyssal water moving toward the Arctic Ocean, understanding the interplay between shelf, slope, and deep waters along the west Spitsbergen margin could be crucial for making projections on future changes in the global thermohaline circulation. © 2019 by the authors.
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28.
  • Hartoog, O. E., et al. (författare)
  • VLT/X-Shooter spectroscopy of the afterglow of the Swift GRB 130606A Chemical abundances and reionisation at z similar to 6
  • 2015
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 580
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: The reionisation of the Universe is a process that is thought to have ended around z similar to 6, as inferred from spectroscopy of distant bright background sources, such as quasars (QSO) and gamma-ray burst (GRB) afterglows. Furthermore, spectroscopy of a GRB afterglow provides insight in its host galaxy, which is often too dim and distant to study otherwise.Aims: For the Swift GRB 130606A at z = 5.913 we have obtained a high S/N spectrum covering the full optical and near-IR wavelength region at intermediate spectral resolution with VLT/X-Shooter. We aim to measure the degree of ionisation of the intergalactic medium (IGM) between z = 5.02-5.84 and to study the chemical abundance pattern and dust content of its host galaxy.Methods: We estimated the UV continuum of the GRB afterglow using a power-law extrapolation, then measured the flux decrement due to absorption at Ly alpha,beta, and gamma wavelength regions. Furthermore, we fitted the shape of the red damping wing of Lya. The hydrogen and metal absorption lines formed in the host galaxy were fitted with Voigt profiles to obtain column densities. We investigated whether ionisation corrections needed to be applied.Results: Our measurements of the Ly alpha-forest optical depth are consistent with previous measurements of QSOs, but have a much smaller uncertainty. The analysis of the red damping wing yields a neutral fraction x(HI) < 0.05 (3 sigma). We obtain column density measurements of H, Al, Si, and Fe; for C, O, S and Ni we obtain limits. The ionisation due to the GRB is estimated to be negligible (corrections < 0.03 dex), but larger corrections may apply due to the pre-existing radiation field (up to 0.4 dex based on sub-DLA studies). Assuming that [Si/Fe] = +0.79 +/- 0.13 is due to dust depletion, the dust-to-metal ratio is similar to the Galactic value.Conclusions: Our measurements confirm that the Universe is already predominantly ionised over the redshift range probed in this work, but was slightly more neutral at z > 5.6. GRBs are useful probes of the ionisation state of the IGM in the early Universe, but because of internal scatter we need a larger statistical sample to draw robust conclusions. The high [Si/Fe] in the host can be due to dust depletion, a-element enhancement, or a combination of both. The very high value of [Al/Fe] = 2.40 +/- 0.78 might be due to a proton capture process and is probably connected to the stellar population history. We estimate the host metallicity to be -1.7 < [M/H] < -0.9 (2%-13% of solar).
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29.
  • Lindström, Ulf, et al. (författare)
  • Effectiveness and treatment retention of TNF inhibitors when used as monotherapy versus comedication with csDMARDs in 15 332 patients with psoriatic arthritis. Data from the EuroSpA collaboration
  • 2021
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 1410-1418
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during treatment with tumour necrosis factor inhibitors (TNFi) is extensively used in psoriatic arthritis (PsA), although the additive benefit remains unclear. We aimed to compare treatment outcomes in patients with PsA treated with TNFi and csDMARD comedication versus TNFi monotherapy. Methods: Patients with PsA from 13 European countries who initiated a first TNFi in 2006-2017 were included. Country-specific comparisons of 1 year TNFi retention were performed by csDMARD comedication status, together with HRs for TNFi discontinuation (comedication vs monotherapy), adjusted for age, sex, calendar year, disease duration and Disease Activity Score with 28 joints (DAS28). Adjusted ORs of clinical remission (based on DAS28) at 12 months were calculated. Between-country heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Secondary analyses stratified according to TNFi subtype (adalimumab/infliximab/etanercept) and restricted to methotrexate as comedication were performed. Results: In total, 15 332 patients were included (62% comedication, 38% monotherapy). TNFi retention varied across countries, with significant heterogeneity precluding a combined estimate. Comedication was associated with better remission rates, pooled OR 1.25 (1.12-1.41). Methotrexate comedication was associated with improved remission for adalimumab (OR 1.45 (1.23-1.72)) and infliximab (OR 1.55 (1.21-1.98)) and improved retention for infliximab. No effect of comedication was demonstrated for etanercept. Conclusion: This large observational study suggests that, as used in clinical practice, csDMARD and TNFi comedication are associated with improved remission rates, and specifically, comedication with methotrexate increases remission rates for both adalimumab and infliximab. © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.
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30.
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31.
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32.
  • Amnell, T, et al. (författare)
  • Now, Next, and Future
  • 2001
  • Ingår i: Modelling and Verification of Parallel Processes (MOVEP'2k), Nantes, France June 19 to 23, 2000. LNCS Tutorial 2067.. ; , s. 100-125
  • Konferensbidrag (refereegranskat)
  •  
33.
  • Bashkanov, M., et al. (författare)
  • Two-pion production in proton-proton collisions
  • 2004
  • Ingår i: Hadron Spectroscopy, Tenth International Conference on Hadron Spectrscopy, Aschaffenburg, Germany 31 August - 6 September 2003. - 0735401977 ; , s. 241-244
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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34.
  • Beaumont, Robin N, et al. (författare)
  • Genome-wide association study of offspring birth weight in 86,577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.
  • 2018
  • Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 1460-2083 .- 0964-6906. ; 27:4, s. 742-756
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86,577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P<5x10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
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35.
  • Felix, Janine F, et al. (författare)
  • Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index.
  • 2016
  • Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:2, s. 389-403
  • Tidskriftsartikel (refereegranskat)abstract
    • A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.
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36.
  • Pape Møller, Anders, et al. (författare)
  • Interaction of climate change with effects of conspecific and heterospecific density on reproduction
  • 2020
  • Ingår i: Oikos. - : Wiley. - 0030-1299 .- 1600-0706. ; 129:12, s. 1807-1819
  • Tidskriftsartikel (refereegranskat)abstract
    • We studied the relationship between temperature and the coexistence of great tit Parus major and blue tit Cyanistes caeruleus, breeding in 75 study plots across Europe and North Africa. We expected an advance in laying date and a reduction in clutch size during warmer springs as a general response to climate warming and a delay in laying date and a reduction in clutch size during warmer winters due to density‐dependent effects. As expected, as spring temperature increases laying date advances and as winter temperature increases clutch size is reduced in both species. Density of great tit affected the relationship between winter temperature and laying date in great and blue tit. Specifically, as density of great tit increased and temperature in winter increased both species started to reproduce later. Density of blue tit affected the relationship between spring temperature and blue and great tit laying date. Thus, both species start to reproduce earlier with increasing spring temperature as density of blue tit increases, which was not an expected outcome, since we expected that increasing spring temperature should advance laying date, while increasing density should delay it cancelling each other out. Climate warming and its interaction with density affects clutch size of great tits but not of blue tits. As predicted, great tit clutch size is reduced more with density of blue tits as temperature in winter increases. The relationship between spring temperature and density on clutch size of great tits depends on whether the increase is in density of great tit or blue tit. Therefore, an increase in temperature negatively affected the coexistence of blue and great tits differently in both species. Thus, blue tit clutch size was unaffected by the interaction effect of density with temperature, while great tit clutch size was affected in multiple ways by these interactions terms.
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37.
  • Pessi, Priscila Jael, et al. (författare)
  • Broad-emission-line dominated hydrogen-rich luminous supernovae
  • 2023
  • Ingår i: Monthly notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 523:4, s. 5315-5340
  • Tidskriftsartikel (refereegranskat)abstract
    • Hydrogen-rich Type II supernovae (SNe II) are the most frequently observed class of core-collapse SNe (CCSNe). However, most studies that analyse large samples of SNe II lack events with absolute peak magnitudes brighter than −18.5 mag at rest-frame optical wavelengths. Thanks to modern surveys, the detected number of such luminous SNe II (LSNe II) is growing. There exist several mechanisms that could produce luminous SNe II. The most popular propose either the presence of a central engine (a magnetar gradually spinning down or a black hole accreting fallback material) or the interaction of supernova ejecta with circumstellar material (CSM) that turns kinetic energy into radiation energy. In this work, we study the light curves and spectral series of a small sample of six LSNe II that show peculiarities in their H α profile, to attempt to understand the underlying powering mechanism. We favour an interaction scenario with CSM that is not dense enough to be optically thick to electron scattering on large scales – thus, no narrow emission lines are observed. This conclusion is based on the observed light curve (higher luminosity, fast decline, blue colours) and spectral features (lack of persistent narrow lines, broad H α emission, lack of H α absorption, weak, or non-existent metal lines) together with comparison to other luminous events available in the literature. We add to the growing evidence that transients powered by ejecta–CSM interaction do not necessarily display persistent narrow emission lines.
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38.
  • Thomassen, Mads, et al. (författare)
  • Clinical, splicing, and functional analysis to classify BRCA2 exon 3 variants : Application of a points-based ACMG/AMP approach
  • 2022
  • Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 43:12, s. 1921-1944
  • Tidskriftsartikel (refereegranskat)abstract
    • Skipping of BRCA2 exon 3 (∆E3) is a naturally occurring splicing event, complicating clinical classification of variants that may alter ∆E3 expression. This study used multiple evidence types to assess pathogenicity of 85 variants in/near BRCA2 exon 3. Bioinformatically predicted spliceogenic variants underwent mRNA splicing analysis using minigenes and/or patient samples. ∆E3 was measured using quantitative analysis. A mouse embryonic stem cell (mESC) based assay was used to determine the impact of 18 variants on mRNA splicing and protein function. For each variant, population frequency, bioinformatic predictions, clinical data, and existing mRNA splicing and functional results were collated. Variant class was assigned using a gene-specific adaptation of ACMG/AMP guidelines, following a recently proposed points-based system. mRNA and mESC analysis combined identified six variants with transcript and/or functional profiles interpreted as loss of function. Cryptic splice site use for acceptor site variants generated a transcript encoding a shorter protein that retains activity. Overall, 69/85 (81%) variants were classified using the points-based approach. Our analysis shows the value of applying gene-specific ACMG/AMP guidelines using a points-based approach and highlights the consideration of cryptic splice site usage to appropriately assign PVS1 code strength.
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39.
  • van der Valk, Ralf J P, et al. (författare)
  • A novel common variant in DCST2 is associated with length in early life and height in adulthood.
  • 2015
  • Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 24:4, s. 1155-68
  • Tidskriftsartikel (refereegranskat)abstract
    • Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
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40.
  • Vaugoyeau, Marie, et al. (författare)
  • Interspecific variation in the relationship between clutch size, laying date and intensity of urbanization in four species of hole-nesting birds
  • 2016
  • Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 6:16, s. 5907-5920
  • Tidskriftsartikel (refereegranskat)abstract
    • The increase in size of human populations in urban and agricultural areas has resulted in considerable habitat conversion globally. Such anthropogenic areas have specific environmental characteristics, which influence the physiology, life history, and population dynamics of plants and animals. For example, the date of bud burst is advanced in urban compared to nearby natural areas. In some birds, breeding success is determined by synchrony between timing of breeding and peak food abundance. Pertinently, caterpillars are an important food source for the nestlings of many bird species, and their abundance is influenced by environmental factors such as temperature and date of bud burst. Higher temperatures and advanced date of bud burst in urban areas could advance peak caterpillar abundance and thus affect breeding phenology of birds. In order to test whether laying date advance and clutch sizes decrease with the intensity of urbanization, we analyzed the timing of breeding and clutch size in relation to intensity of urbanization as a measure of human impact in 199 nest box plots across Europe, North Africa, and the Middle East (i.e., the Western Palearctic) for four species of hole-nesters: blue tits (Cyanistes caeruleus), great tits (Parus major), collared flycatchers (Ficedula albicollis), and pied flycatchers (Ficedula hypoleuca). Meanwhile, we estimated the intensity of urbanization as the density of buildings surrounding study plots measured on orthophotographs. For the four study species, the intensity of urbanization was not correlated with laying date. Clutch size in blue and great tits does not seem affected by the intensity of urbanization, while in collared and pied flycatchers it decreased with increasing intensity of urbanization. This is the first large-scale study showing a species-specific major correlation between intensity of urbanization and the ecology of breeding. The underlying mechanisms for the relationships between life history and urbanization remain to be determined. We propose that effects of food abundance or quality, temperature, noise, pollution, or disturbance by humans may on their own or in combination affect laying date and/or clutch size.
  •  
41.
  • Barringer, R., et al. (författare)
  • Ray Accelerator : Efficient and Flexible Ray Tracing on a Heterogeneous Architecture
  • 2017
  • Ingår i: Computer Graphics Forum. - : Wiley. - 0167-7055. ; 36:8, s. 166-177
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a hybrid ray tracing system, where the work is divided between the CPU cores and the GPU in an integrated chip, and communication occurs via shared memory. Rays are organized in large packets that can be distributed among the two units as needed. Testing visibility between rays and the scene is mostly performed using an optimized kernel on the GPU, but the CPU can help as necessary. The CPU cores typically handle most or all shading, which makes it easy to support complex appearances. For efficiency, the CPU cores shade whole batches of rays by sorting them on material and shading each material using a vectorized kernel. In addition, we introduce a method to support light paths with arbitrary recursion, such as multiple recursive Whitted-style ray tracing and adaptive sampling where the result of a ray is examined before sending the next, while still batching up rays for the benefit of GPU-accelerated traversal and vectorized shading. This allows our system to achieve high rendering performance while maintaining the flexibility to accommodate different rendering algorithms.
  •  
42.
  • Bexelius, T., et al. (författare)
  • Stress among medical students during clinical courses : a longitudinal study using contextual activity sampling system
  • 2019
  • Ingår i: International Journal of Medical Education. - : IJME. - 2042-6372. ; 10, s. 68-74
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To investigate medical students’ experiences of stress and other emotions related to their professional roles, as defined by the CanMEDS framework, by using the Contextual Activity Sampling System (CASS).Methods: Ninety-eight medical students agreed to participate of whom 74 completed this longitudinal cohort study. Data was collected between 6th and 8th term via CASS methodology: A questionnaire was e-mailed to the participants every 3rd week (21questionnaires/measurements) during clinical rotations and scientific project work term. Emotions were measured by a 7-point Likert scale (e.g., maximum stress = 7). Answers were registered through mobile technology. We used a linear mixed-model regression approach to study the association between stress over time in relation to socio-demographic and learning activities related to CanMEDS roles.Results: Participants completed 1390 questionnaires. Mean stress level over all time points was 3.6. Stress was reported as highest during the scientific project term. Learning activities related to ‘Communicator,’ ‘Collaborator,’ ‘Scholar,’ ‘Manager’ and ‘Professional’ were associated with increased stress, e.g. ’Scholar’ increased stress with 0.5 points (t=3.91, p<0.001). A reduced level of stress was associated with ’Health Advocate’ of 0.39 points (t=-2.15, p=0.03). No association between perceived stress and demographic factors, such as gender or age was found.Conclusions: An association between different learning activities related to CanMEDS Roles and feelings of stress were noted. The CASS methodology was found to be useful when observing learning experiences and might support educational development by identifying course activities linked to stress.
  •  
43.
  • Bruder, CEG, et al. (författare)
  • High resolution deletion analysis of constitutional DNA from neurofibromatosis type 2 (NF2) patients using microarray-CGH
  • 2001
  • Ingår i: Human Molecular Genetics. - Oxford, United Kingdom : Oxford University Press. - 0964-6906 .- 1460-2083. ; 1, s. 271-
  • Tidskriftsartikel (refereegranskat)abstract
    • Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder whose hallmark is bilateral vestibular schwannoma. It displays a pronounced clinical heterogeneity with mild to severe forms. The NF2 tumor suppressor (merlin/schwannomin) has been cloned and extensively analyzed for mutations in patients with different clinical variants of the disease. Correlation between the type of the NF2 gene mutation and the patient phenotype has been suggested to exist. However, several independent studies have shown that a fraction of NF2 patients with various phenotypes have constitutional deletions that partly or entirely remove one copy of the NF2 gene. The purpose of this study was to examine a 7 Mb interval in the vicinity of the NF2 gene in a large series of NF2 patients in order to determine the frequency and extent of deletions. A total of 116 NF2 patients were analyzed using high-resolution array-comparative genomic hybridization (CGH) on an array covering at least 90% of this region of 22q around the NF2 locus. Deletions, which remove one copy of the entire gene or are predicted to truncate the schwannomin protein, were detected in 8 severe, 10 moderate and 6 mild patients. This result does not support the correlation between the type of mutation affecting the NF2 gene and the disease phenotype. This work also demonstrates the general usefulness of the array-CON methodology for rapid and comprehensive detection of small (down to 40 kb) heterozygous and/or homozygous deletions occurring in constitutional or tumor-derived DNA.
  •  
44.
  • Christensen, L. H., et al. (författare)
  • Reduced mortality for women with mammography-detected breast cancer in east Denmark and south Sweden
  • 2006
  • Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 42:16, s. 2773-2780
  • Tidskriftsartikel (refereegranskat)abstract
    • The 5-year relative survival from breast cancer in Denmark is 10 percentage points lower than in Sweden. This difference has been demonstrated previously as being caused partly by more involved lymph nodes and larger tumours in Denmark. Sweden has had nationwide mammography-screening coverage since 1991, whereas this is still in its infancy in Denmark. In the search for an explanation for the remaining survival difference, patient delay was a likely candidate. This study compared patient delay and mammography-detection between two national regions. Data on patient delay and mammography were obtained from hospital records from 1989 and 1994, and analysed using Cox proportional hazard analysis of death within the first 5 years, with the factors age, country, delay/mammography detection and established patho-anatomic variables. A comparison of patient delay and mammography detection in 1989 and 1994 showed more mammography-detected tumours in south Sweden and more women with long delay in east Denmark. Mammography detection, but not long patient delay, had a significant effect on the death hazard when adjusting for patho-anatomic risk factors. The hazard ratio was not eliminated in 1989, but in 1994, the hazard ratio between east Denmark and south Sweden was reduced from 1.3 to 1.1. In conclusion, patient delay did not appear to have any effect on 5-year survival when adjusting for patho-anatomic factors, but tumour detection by mammography affected survival favourably and partly explained the survival difference between east Denmark and south Sweden. (c) 2006 Elsevier Ltd. All rights reserved.
  •  
45.
  • Hatem, Gad, et al. (författare)
  • Mapping the cord blood transcriptome of pregnancies affected by early maternal anemia to identify signatures of fetal programming
  • 2022
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 107:5, s. 1303-1316
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Anemia during early pregnancy (EP) is common in developing countries and is associated with adverse health consequences for both mother and children. Offspring of women with EP anemia often have low birth-weight, the latter being a risk factor for cardiometabolic diseases including type 2 diabetes (T2D) later in life. Mechanisms underlying developmental programming of adult cardiometabolic disease include epigenetic and transcriptional alterations potentially detectable in umbilical cord blood (UCB) at time of birth.METHODS: We leveraged global transcriptome- and accompanying epigenome-wide changes in 48 UCB from newborns of EP-anemic Tanzanian mothers and 50 controls to identify differentially expressed genes (DEG) in UCB exposed to maternal EP-anemia. DEGs were assessed for association with neonatal anthropometry and cord insulin levels. These genes were further studied in expression data from human fetal pancreas and adult islets to understand their role in beta-cell development and/or function.RESULTS: The expression of 137 genes was altered in UCB of newborns exposed to maternal EP anemia. These putative signatures of fetal programming which included the birth-weight locus LCORL, were potentially mediated by epigenetic changes in 27 genes and associated with neonatal anthropometry. Among the DEGs were P2RX7, PIK3C2B, and NUMBL which potentially influence beta-cell development. Insulin levels were lower in EP anemia exposed UCB, supporting the notion of developmental programming of pancreatic beta-cell dysfunction and subsequently increased risk of T2D in offspring of EP anemic mothers.CONCLUSIONS: Our data provide proof-of-concept on distinct transcriptional and epigenetic changes detectable in UCB from newborns exposed to maternal EP anemia.
  •  
46.
  • Hirscher, Michael, et al. (författare)
  • Materials for hydrogen-based energy storage - past, recent progress and future outlook
  • 2020
  • Ingår i: Journal of Alloys and Compounds. - : Elsevier BV. - 0925-8388 .- 1873-4669. ; 827
  • Tidskriftsartikel (refereegranskat)abstract
    • Globally, the accelerating use of renewable energy sources, enabled by increased efficiencies and reduced costs, and driven by the need to mitigate the effects of climate change, has significantly increased research in the areas of renewable energy production, storage, distribution and end-use. Central to this discussion is the use of hydrogen, as a clean, efficient energy vector for energy storage. This review, by experts of Task 32, Hydrogen-based Energy Storage of the International Energy Agency, Hydrogen TCP, reports on the development over the last 6 years of hydrogen storage materials, methods and techniques, including electrochemical and thermal storage systems. An overview is given on the background to the various methods, the current state of development and the future prospects. The following areas are covered; porous materials, liquid hydrogen carriers, complex hydrides, intermetallic hydrides, electrochemical storage of energy, thermal energy storage, hydrogen energy systems and an outlook is presented for future prospects and research on hydrogen-based energy storage.
  •  
47.
  • Lemcke, S., et al. (författare)
  • Nerve conduction velocity is regulated by the inositol polyphosphate-4-phosphatase II gene
  • 2014
  • Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 184:9, s. 2420-2429
  • Tidskriftsartikel (refereegranskat)abstract
    • Impairment of nerve conduction is common in neurodegenerative and neuroinflammatory diseases such as multiple sclerosis (MS), and measurement of evoked potentials (visual, motor, or sensory) has been widely used for diagnosis and recently also as a prognostic marker for MS. We used a classical genetic approach to identify novel genes controlling nerve conduction. First, we used quantitative trait mapping in F2 progeny of B10/SJL mice to identify EAE31, a locus controlling latency of motor evoked potentials (MEPs) and clinical onset of experimental autoimmune encephalomyelitis. Then, by combining congenic mapping, in silico haplotype analyses, and comparative genomics we identified inositol polyphosphate-4-phosphatase, type II (Inpp4b) as the quantitative trait gene for EAE31. Sequence variants of Inpp4b (C/A, exon 13; A/C, exon 14) were identified as differing among multiple mouse strains and correlated with individual cortical MEP latency differences. To evaluate the functional relevance of the amino acid exchanges at positions S474R and H548P, we generated transgenic mice carrying the longer-latency allele (Inpp4b(474R/548P)) in the C57BL/6J background. Inpp4b(474R/548P) mice exhibited significantly longer cortical MEP latencies (4.5 +/- 0.22 ms versus 3.7 +/- 0.13 ms; P = 1.04 x 10(-9)), indicating that INPP4B regulates nerve conduction velocity. An association of an INPP4B polymorphism (rs13102150) with MS was observed in German and Spanish MS cohorts (3676 controls and 911 cases) (P = 8.8 x 10(-3)).
  •  
48.
  •  
49.
  • Micheli, A, et al. (författare)
  • Cancer prevalence in European registry areas
  • 2002
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 13:6, s. 840-865
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Information on cancer prevalence is of major importance for health planning and resource allocation. However, systematic information on cancer prevalence is largely unavailable. MATERIALS AND METHODS: Thirty-eight population-based cancer registries from 17 European countries, participating in EUROPREVAL, provided data on almost 3 million cancer patients diagnosed from 1970 to 1992. Standardised data collection and validation procedures were used and the whole data set was analysed using proven methodology. The prevalence of stomach, colon, rectum, lung, breast, cervix uteri, corpus uteri and prostate cancer, as well as of melanoma of skin, Hodgkin's disease, leukaemia and all malignant neoplasms combined, were estimated for the end of 1992. RESULTS: There were large differences between countries in the prevalence of all cancers combined; estimates ranged from 1170 per 100000 in the Polish cancer registration areas to 3050 per 100000 in southern Sweden. For most cancers, the Swedish, Swiss, German and Italian areas had high prevalence, and the Polish, Estonian, Slovakian and Slovenian areas had low prevalence. Of the total prevalent cases, 61% were women and 57% were 65 years of age or older. Cases diagnosed within 2 years of the reference date formed 22% of all prevalent cases. Breast cancer accounted for 34% of all prevalent cancers in females and colorectal cancer for 15% in males. Prevalence tended to be high where cancer incidence was high, but the prevalence was highest in countries where survival was also high. Prevalence was low where general mortality was high (correlation between general mortality and the prevalence of all cancers = -0.64) and high where gross domestic product was high (correlation = +0.79). Thus, the richer areas of Europe had higher prevalence, suggesting that prevalence will increase with economic development. CONCLUSIONS: EUROPREVAL is the largest project on prevalence conducted to date. It has provided complete and accurate estimates of cancer prevalence in Europe, constituting essential information for cancer management. The expected increases in prevalence with economic development will require more resources; allocation to primary prevention should therefore be prioritised.
  •  
50.
  • Möller, Claes, 1950-, et al. (författare)
  • Late otoneurological findings due to industrial solvent exposure
  • 2000
  • Ingår i: Transactions of the XXth Regular Meeting of the Bárány Society, Würzburg, 11-12 September 1998, ICS 1201. - Amsterdam : Elsevier. - 9780444500120 ; , s. 487-493
  • Konferensbidrag (refereegranskat)
  •  
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