| 1. |
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| 2. |
- Singh, B. P., et al.
(författare)
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Experimental access to Transition Distribution Amplitudes with the PANDA experiment at FAIR
- 2015
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Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 51:8
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Tidskriftsartikel (refereegranskat)abstract
- Baryon-to-meson Transition Distribution Amplitudes (TDAs) encoding valuable new information on hadron structure appear as building blocks in the collinear factorized description for several types of hard exclusive reactions. In this paper, we address the possibility of accessing nucleon-to-pion (pi N) TDAs from (p) over barp -> e(+)e(-)pi(0) reaction with the future PANDA detector at the FAIR facility. At high center-of-mass energy and high invariant mass squared of the lepton pair q(2), the amplitude of the signal channel (p) over barp -> e(+)e(-)pi(0) admits a QCD factorized description in terms of pi N TDAs and nucleon Distribution Amplitudes (DAs) in the forward aid backward kinematic regimes. Assuming the validity of this factorized description, we perform feasibility studies for measuring (p) over barp -> e(+)e(-)pi(0) with the PANDA detector. Detailed simulations on signal reconstruction efficiency as well as on rejection of the most severe background channel, i.e. (p) over barp -> pi(+)pi(-)pi(0) were performed for the center-of-mass energy squared s = 5 GeV2 and s = 10 GeV2, in the kinematic regions 3.0 < q(2) < 4.3 GeV2 and 5 < q(2) < 9 GeV2, respectively, with a neutral pion scattered in the forward or backward cone vertical bar cos theta(pi 0)vertical bar > 0.5 in the proton-antiproton center-of-mass frame. Results of the simulation show that the particle identification capabilities of the PANDA detector will allow to achieve a background rejection factor of 5 . 10(7) (1 . 10(7)) at low (high) q(2) for s = 5 GeV2, and of 1 . 10(8) (6 . 10(6)) at low (high) q(2) for s = 10 GeV2, while keeping the signal reconstruction efficiency at around 40%. At both energies, a clean lepton signal can be reconstructed with the expected statistics corresponding to 2 of integrated luminosity. The cross sections obtained from the simulations are used to show that a test of QCD collinear factorization can be done at the lowest order by measuring scaling laws and angular distributions. The future measurement of the signal channel cross section with PANDA will provide a new test of the perturbative QCD description of a novel class of hard exclusive reactions and will open the possibility of experimentally accessing pi N TDAs.
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| 3. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 4. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 5. |
- Ackermann, M., et al.
(författare)
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Fermi LAT observations of cosmic-ray electrons from 7 GeV to 1 TeV
- 2010
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Ingår i: PHYSICAL REVIEW D. - 1550-7998. ; 82:9, s. 092004-
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of our analysis of cosmic-ray electrons using about 8 x 10(6) electron candidates detected in the first 12 months on-orbit by the Fermi Large Area Telescope. This work extends our previously published cosmic-ray electron spectrum down to 7 GeV, giving a spectral range of approximately 2.5 decades up to 1 TeV. We describe in detail the analysis and its validation using beam-test and on-orbit data. In addition, we describe the spectrum measured via a subset of events selected for the best energy resolution as a cross-check on the measurement using the full event sample. Our electron spectrum can be described with a power law proportional to E-3.08+/-0.05 with no prominent spectral features within systematic uncertainties. Within the limits of our uncertainties, we can accommodate a slight spectral hardening at around 100 GeV and a slight softening above 500 GeV.
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| 6. |
- Barucca, G., et al.
(författare)
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Study of excited Ξ baryons with the P¯ ANDA detector
- 2021
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Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
-
Tidskriftsartikel (refereegranskat)abstract
- The study of baryon excitation spectra provides insight into the inner structure of baryons. So far, most of the world-wide efforts have been directed towards N∗ and Δ spectroscopy. Nevertheless, the study of the double and triple strange baryon spectrum provides independent information to the N∗ and Δ spectra. The future antiproton experiment P¯ANDA will provide direct access to final states containing a Ξ¯ Ξ pair, for which production cross sections up to μb are expected in p¯p reactions. With a luminosity of L= 10 31 cm- 2 s- 1 in the first phase of the experiment, the expected cross sections correspond to a production rate of ∼106events/day. With a nearly 4 π detector acceptance, P¯ANDA will thus be a hyperon factory. In this study, reactions of the type p¯p → Ξ¯ +Ξ∗ - as well as p¯p → Ξ¯ ∗ +Ξ- with various decay modes are investigated. For the exclusive reconstruction of the signal events a full decay tree fit is used, resulting in reconstruction efficiencies between 3 and 5%. This allows high statistics data to be collected within a few weeks of data taking.
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| 7. |
- Barucca, G., et al.
(författare)
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The potential of Λ and Ξ- studies with PANDA at FAIR
- 2021
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Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
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Tidskriftsartikel (refereegranskat)abstract
- The antiproton experiment PANDA at FAIR is designed to bring hadron physics to a new level in terms of scope, precision and accuracy. In this work, its unique capability for studies of hyperons is outlined. We discuss ground-state hyperons as diagnostic tools to study non-perturbative aspects of the strong interaction, and fundamental symmetries. New simulation studies have been carried out for two benchmark hyperon-antihyperon production channels: p¯ p→ Λ¯ Λ and p¯ p→ Ξ¯ +Ξ-. The results, presented in detail in this paper, show that hyperon-antihyperon pairs from these reactions can be exclusively reconstructed with high efficiency and very low background contamination. In addition, the polarisation and spin correlations have been studied, exploiting the weak, self-analysing decay of hyperons and antihyperons. Two independent approaches to the finite efficiency have been applied and evaluated: one standard multidimensional efficiency correction approach, and one efficiency independent approach. The applicability of the latter was thoroughly evaluated for all channels, beam momenta and observables. The standard method yields good results in all cases, and shows that spin observables can be studied with high precision and accuracy already in the first phase of data taking with PANDA.
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| 8. |
- Collaboration, The PANDA, et al.
(författare)
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Feasibility studies of time-like proton electromagnetic form factors at PANDA at FAIR
- 2016
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Ingår i: European Physical Journal A. - : Springer Publishing Company. - 1434-6001 .- 1434-601X. ; 52:10
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Tidskriftsartikel (refereegranskat)abstract
- Simulation results for future measurements of electromagnetic proton form factors at P ¯ ANDA (FAIR) within the PandaRoot software framework are reported. The statistical precision with which the proton form factors can be determined is estimated. The signal channel p¯ p→ e+e- is studied on the basis of two different but consistent procedures. The suppression of the main background channel, i.e.p¯ p→ π+π-, is studied. Furthermore, the background versus signal efficiency, statistical and systematical uncertainties on the extracted proton form factors are evaluated using two different procedures. The results are consistent with those of a previous simulation study using an older, simplified framework. However, a slightly better precision is achieved in the PandaRoot study in a large range of momentum transfer, assuming the nominal beam conditions and detector performance.
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| 9. |
- Singh, B., et al.
(författare)
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Study of doubly strange systems using stored antiprotons
- 2016
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Ingår i: Nuclear Physics A. - : Elsevier. - 0375-9474 .- 1873-1554. ; 954, s. 323-340
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Tidskriftsartikel (refereegranskat)abstract
- Bound nuclear systems with two units of strangeness are still poorly known despite their importance for many strong interaction phenomena. Stored antiprotons beams in the GeV range represent an unparalleled factory for various hyperon-antihyperon pairs. Their outstanding large production probability in antiproton collisions will open the floodgates for a series of new studies of systems which contain two or even more units of strangeness at the PANDA experiment at FAIR. For the first time, high resolution gamma-spectroscopy of doubly strange Lambda Lambda-hypernuclei will be performed, thus complementing measurements of ground state decays of Lambda Lambda-hypernuclei at J-PARC or possible decays of particle unstable hypernuclei in heavy ion reactions. High resolution spectroscopy of multistrange Xi(-) -atoms will be feasible and even the production of Omega(-) -atoms will be within reach. The latter might open the door to the vertical bar S vertical bar = 3 world in strangeness nuclear physics, by the study of the hadronic Omega(-) -nucleus interaction. For the first time it will be possible to study the behavior of Xi(+) in nuclear systems under well controlled conditions.
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| 10. |
- Aartsen, M. G., et al.
(författare)
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The IceCube Neutrino Observatory : instrumentation and online systems
- 2017
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Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The IceCube Neutrino Observatory is a cubic-kilometer-scale high-energy neutrino detector built into the ice at the South Pole. Construction of IceCube, the largest neutrino detector built to date, was completed in 2011 and enabled the discovery of high-energy astrophysical neutrinos. We describe here the design, production, and calibration of the IceCube digital optical module (DOM), the cable systems, computing hardware, and our methodology for drilling and deployment. We also describe the online triggering and data filtering systems that select candidate neutrino and cosmic ray events for analysis. Due to a rigorous pre-deployment protocol, 98.4% of the DOMs in the deep ice are operating and collecting data. IceCube routinely achieves a detector uptime of 99% by emphasizing software stability and monitoring. Detector operations have been stable since construction was completed, and the detector is expected to operate at least until the end of the next decade.
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| 11. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 12. |
- Erni, W., et al.
(författare)
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Technical design report for the PANDA (AntiProton Annihilations at Darmstadt) Straw Tube Tracker
- 2013
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Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 49:2
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Tidskriftsartikel (refereegranskat)abstract
- This document describes the technical layout and the expected performance of the Straw Tube Tracker (STT), the main tracking detector of the PANDA target spectrometer. The STT encloses a Micro-Vertex-Detector (MVD) for the inner tracking and is followed in beam direction by a set of GEM stations. The tasks of the STT are the measurement of the particle momentum from the reconstructed trajectory and the measurement of the specific energy loss for a particle identification. Dedicated simulations with full analysis studies of certain proton-antiproton reactions, identified as being benchmark tests for the whole PANDA scientific program, have been performed to test the STT layout and performance. The results are presented, and the time lines to construct the STT are described.
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| 13. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 14. |
- Sønderby, Ida E., et al.
(författare)
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1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
- 2021
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
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| 15. |
- van der Meer, Dennis, et al.
(författare)
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Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition
- 2020
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 77:4, s. 420-430
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
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| 16. |
- Sonderby, Ida E., et al.
(författare)
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Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
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Tidskriftsartikel (refereegranskat)abstract
- Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
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| 17. |
- Wessel, Jennifer, et al.
(författare)
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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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| 18. |
- Abbasi, R., et al.
(författare)
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Measurement of acoustic attenuation in South Pole ice
- 2011
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 34:6, s. 382-393
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Tidskriftsartikel (refereegranskat)abstract
- Using the South Pole Acoustic Test Setup (SPATS) and a retrievable transmitter deployed in holes drilled for the IceCube experiment, we have measured the attenuation of acoustic signals by South Pole ice at depths between 190 m and 500 m. Three data sets, using different acoustic sources, have been analyzed and give consistent results. The method with the smallest systematic uncertainties yields an amplitude attenuation coefficient alpha = 3.20 +/- 0.57 km(-1) between 10 and 30 kHz, considerably larger than previous theoretical estimates. Expressed as an attenuation length, the analyses give a consistent result for lambda equivalent to 1/alpha of similar to 300 m with 20% uncertainty. No significant depth or frequency dependence has been found.
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| 19. |
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| 20. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 21. |
- Varju, Katalin, et al.
(författare)
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Experimental studies of attosecond pulse trains
- 2005
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Ingår i: Laser Physics. - 1054-660X. ; 15:6, s. 888-898
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Tidskriftsartikel (refereegranskat)abstract
- We present experimental measurements of attosecond pulse trains. The characterization of the pulses uses a spectral interferometry technique that is implemented with a Mach-Zehnder interferometer. This allows us to manipulate independently the pump and probe pulses for a wide range of applications. By letting the attosecond pulses pass through metallic films, we can in particular compensate for the intrinsic chirp of the attosecond pulses corresponding to the plateau spectral region, thus getting pulses as short as 170 attoseconds-only 1.2 optical cycles at the central frequency. The measurement technique is also applicable for determination of the group delay of thin XUV-transparent films and relative delay in the photoionization process. Our experimental method is applied to attosecond pulse trains created by 35- and 9-fs laser pulses, and the shortest train observed consists of three or four pulses.
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| 22. |
- Bonagas, Nadilly, et al.
(författare)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 23. |
- Duffy, J. E., et al.
(författare)
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Biodiversity mediates top-down control in eelgrass ecosystems: a global comparative-experimental approach
- 2015
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 18:7, s. 696-705
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Tidskriftsartikel (refereegranskat)abstract
- Nutrient pollution and reduced grazing each can stimulate algal blooms as shown by numerous experiments. But because experiments rarely incorporate natural variation in environmental factors and biodiversity, conditions determining the relative strength of bottom-up and top-down forcing remain unresolved. We factorially added nutrients and reduced grazing at 15 sites across the range of the marine foundation species eelgrass (Zostera marina) to quantify how top-down and bottom-up control interact with natural gradients in biodiversity and environmental forcing. Experiments confirmed modest top-down control of algae, whereas fertilisation had no general effect. Unexpectedly, grazer and algal biomass were better predicted by cross-site variation in grazer and eelgrass diversity than by global environmental gradients. Moreover, these large-scale patterns corresponded strikingly with prior small-scale experiments. Our results link global and local evidence that biodiversity and top-down control strongly influence functioning of threatened seagrass ecosystems, and suggest that biodiversity is comparably important to global change stressors.
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| 24. |
- Gustafsson, Per E, 1981-, et al.
(författare)
-
Cortisol levels and psychosocial factors in preadolescent children
- 2006
-
Ingår i: Stress and Health. - : Wiley. - 1532-3005 .- 1532-2998. ; 22:1, s. 3-9
-
Tidskriftsartikel (refereegranskat)abstract
- Regarding the relationship between psychosocial factors and health, one model of explanation states that psychosocial stress constitutes a principal mediator connecting psychosocial factors to health outcome, affecting the body through psychobiological mechanisms. This relationship has scarcely been studied in children. In the present study the relation between diurnal cortisol secretion and psychosocial factors [socio-economic status (SES), immigrant status and impact of psychiatric symptoms] was investigated in a normal population of 6-12 year old children (n = 273). Salivary cortisol levels were measured in the early morning, late morning and in the evening during three consecutive days. Parents answered demographic questionnaires and teachers answered psychiatric questionnaires concerning the children. Children exposed to one or more of the factors of psychosocial load (n = 117) had significantly higher morning (p < 0.001) and evening (p = 0.029) cortisol levels as well as total daily cortisol secretion [measured by the area under the curve (AUC), p = 0.003] compared to the group of children with none of the factors (n = 156). Different psychosocial stressors seemed to influence different parts of the diurnal cortisol curve. In conclusion, this study indicates that even children exposed to a moderate degree of psychosocial load differ in their cortisol levels compared to non-exposed children.
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| 25. |
- Gustafsson, Per E., 1981-, et al.
(författare)
-
Diurnal cortisol levels and cortisol response in youths with obsessive-compulsive disorder
- 2008
-
Ingår i: Neuropsychobiology. - : S. Karger AG. - 0302-282X .- 1423-0224. ; 57:1-2, s. 14-21
-
Tidskriftsartikel (refereegranskat)abstract
- <i>Background/Aims:</i> Recent results indicate a role of the hypothalamic-pituitary-adrenal (HPA) axis in the pathophysiology of obsessive-compulsive disorder (OCD). Although childhood onset is common, the HPA axis has scarcely been studied in young OCD subjects. Therefore, the present study aimed at examining basal and response levels of salivary cortisol in a sample of young OCD subjects. <i>Methods:</i> Twenty-three children and adolescents with DSM-IV OCD were compared to a reference group of school children (n = 240–336). The basal cortisol rhythm was measured through saliva samples 3 times/day. The cortisol response to a psychological stressor (exposure therapy in the OCD group and a fire alarm in the reference group) was also examined. <i>Results:</i> Compared to the reference group, OCD subjects displayed higher early-morning cortisol values (p = 0.005) with no difference between the late-morning and evening values. The cortisol levels in the OCD group diminished in response to the psychological stressor, compared to a positive response in the reference group (p < 0.001). No relation was found between cortisol and clinical parameters. <i>Conclusion:</i> These results support the idea that HPA hyperactivity, commonly found in adult OCD patients, is also present at an earlier stage of development, with specificity for the early-morning peak.
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| 26. |
- Gustafsson, Per E, et al.
(författare)
-
Diurnal cortisol levels, psychiatric symptoms and sense of coherence in abused adolescents.
- 2010
-
Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 64:1, s. 27-31
-
Tidskriftsartikel (refereegranskat)abstract
- Background. The role of the hypothalamic-pituitary-adrenal (HPA) axis in psychiatric disorders following trauma is poorly studied and most studies have been done on adults. Aims. To investigate the association of mental well-being and diurnal cortisol in abused adolescents. Methods. The present cross-sectional study examined diurnal salivary cortisol (measured three times a day during three days) in relation to psychiatric symptoms (Trauma Symptoms Checklist for Children) and the salutogenic construct “sense of coherence”, in 15 adolescents exposed to childhood abuse. Results. Significant correlations were found between symptoms and sense of coherence versus early and late morning cortisol concentrations. The correlations were most consistent for internalizing and externalizing symptoms, and somewhat less for post-traumatic symptoms and sense of coherence. In contrast, evening cortisol did not correlate with any of the psychological measures. Conclusion. These results extend previous research findings by pointing towards a relation between symptoms and higher morning cortisol and accentuated diurnal cortisol variation in abused adolescent as opposed to lower basal cortisol and a flattening of the cortisol rhythm repeatedly observed in traumatized adults. Clinical implications. The pathophysiology of the impact of trauma on youth, including the impact on biological stress systems, are important for an understanding of the consequences of trauma and may serve as a basis for the development of new treatment options.
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| 27. |
- Gustafsson, Per E, et al.
(författare)
-
Does quantity have a quality all its own? Cumulative adversity and up- and down-regulation of circadian salivary cortisol levels in healthy children.
- 2010
-
Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 35:9, s. 1410-1415
-
Tidskriftsartikel (refereegranskat)abstract
- Findings have been divergent regarding the direction of basal cortisol dysregulations resulting from stressor exposure, and seem to differ between young people and adults. Accumulated stress exposure has been suggested to be a risk factor for the development of hypocortisolism. This cross-sectional study aims to examine the impact of cumulative adversity, i.e., the number of adversities, on diurnal salivary cortisol levels, including the cortisol awakening response (CAR), in children without psychiatric disorder. The sample consisted of 130 children (mean age 12.8 years), representing one in each twin pair included in the population-based Child and Adolescent Twin Study in Sweden (CATSS). Information about socioeconomic disadvantage, negative life events and potentially traumatic life events were collected by telephone interview and questionnaires, with parents as informants. Salivary cortisol sampling was performed in the home during two school days: at awakening, +30 min post-awakening, and at bedtime. Results showed that the number of adversities was related to the CAR, diurnal decline and +30 min post-awakening cortisol levels. Children with a moderate amount of cumulative adversity displayed high cortisol measures, while those with a high amount (3 or more) of adversities instead showed levels similar to the non-exposed group, yielding an inverse U-pattern of the association between cortisol and adversity. These results indicate that the accumulation of adversity might be an explanation of patterns of basal cortisol up-regulation in children and that those most severely exposed can exhibit an early stage of down-regulation, an issue which should be further examined in longitudinal studies.
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| 28. |
- Gustafsson, Per E, et al.
(författare)
-
Effects of an outdoor education intervention on the mental health of schoolchildren
- 2012
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Ingår i: Journal of Adventure Education and Outdoor Learning. - : Routledge. - 1472-9679 .- 1754-0402. ; 12:1, s. 63-79
-
Tidskriftsartikel (refereegranskat)abstract
- This study aimed at examining the effects of an outdoor educational intervention on the mental health of schoolchildren. Two elementary schools participated (N = 230); one experimental school where the intervention was implemented, and the other a reference school. Demographic questions and the Strengths and Difficulties Questionnaire were completed by the parents. An outdoor educational intervention was implemented at the experimental school, and the data collection was repeated after one year. The results point towards a small but non-significant improvement in mental health at the experimental school while adjusting for demographics. However, this effect was significantly moderated by gender: boys generally fared better than girls at the intervention school, relative to the reference school. The results indicate that it may be important to address gender issues when educational programmes are implemented in schools.
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| 29. |
- Gustafsson, Per E, 1981-
(författare)
-
Psychosocial Stress, Mental Health and Salivary Cortisol in Children and Adolescents
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Stressful experiences and conditions in childhood influence the health and well-being of the growing individual, and can also confer a long-lasting impact into adult life. Delineating the social, mental and biological aspects of stress in children and adolescents is therefore of great concern for human beings. Despite these notions, much knowledge is lacking regarding stress in childhood.This thesis aimed at examining diverse aspects of stress in children and adolescents: associations between social conditions, traumatic life events, mental health, and salivary cortisol as a measure of the activity of a major physiological stress system. Cross-sectional samples included two non-clinical samples of school-aged children (N=240-336) and adolescents (N =400), and two clinical samples of children with obsessive-compulsive disorder (OCD) (N =23) and adolescents who had experienced childhood abuse (N =15). Main measures were salivary cortisol sampled three times a day, and questionnaires to teachers, parents and children with questions about each child’s mental health, traumatic life events and about the socioeconomic situation of the parents.The main findings include observation of 1) higher cortisol levels in children with a moderate level of psychosocial burden (low socioeconomic status, immigrant family, social impairment of mental health problems), 2) higher cortisol levels in children with OCD who also displayed a tendency to decreasing cortisol in the face of an acute stressor, and 3) cortisol was positively related to mental health problems in abused adolescents. Furthermore, the deleterious effect of 4) traumatic events involving a social dimension, interpersonal traumas, and 5) cumulative traumatic events, polytraumatization, on the mental health of children and adolescents was indicated.The findings are discussed with respect to the complex interactions between social, mental and biological aspects of children and adolescents. The consequences of adverse experiences in childhood may represent pathways to future health problems. Consideration of the social circumstances in childhood might in the future guide public health policies and the identification of target groups for preventive interventions as well as leading to improvements in treatment for children exposed to severe stress.
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| 30. |
- Gustafsson, Per E., 1981-, et al.
(författare)
-
Sociocultural Disadvantage, Traumatic Life Events, and Psychiatric Symptoms in Preadolescent Children
- 2009
-
Ingår i: American Journal of Orthopsychiatry. - : American Psychological Association (APA). - 0002-9432 .- 1939-0025. ; 79:3, s. 387-397
-
Tidskriftsartikel (refereegranskat)abstract
- Previous research has demonstrated impact of psychosocial adversity on the mental health of children. This cross-sectional study examined the differential relationships between life-time exposure to interpersonal and non-interpersonal traumatic life events as well as sociocultural factors (family social class and immigrant family), and the level of externalizing versus internalizing symptoms. Participants included 258 children aged 6 to 12 years from two Swedish elementary schools. Information was obtained from their parents by means of questionnaires (a demographic form including information about parental occupation and country of origin, the Strengths and Difficulties Questionnaire and the Life Incidence of Traumatic Events checklist). While controlling for gender, age and the other symptom dimension, the sociocultural factors were associated to internalizing but not to externalizing symptoms. In contrast, traumatic life events and especially interpersonal traumas related to externalizing symptoms but not to internalizing symptoms. These findings provide some support for specificity of psychosocial adversities and for the importance of interpersonal traumas, in the impact on child mental health.
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| 31. |
- Gustafsson, Per, et al.
(författare)
-
Heritability of cortisol regulation in children.
- 2011
-
Ingår i: Twin research and human genetics : the official journal of the International Society for Twin Studies. - : Australian Academic Press. - 1832-4274 .- 1839-2628. ; 14:6, s. 553-61
-
Tidskriftsartikel (refereegranskat)abstract
- The normal development of cortisol regulation during childhood is thought to be influenced by a complex interplay between environmental and genetic factors.
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| 32. |
- Lindgren, Johan, et al.
(författare)
-
Soft-tissue evidence for homeothermy and crypsis in a Jurassic ichthyosaur
- 2018
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 564:7736
-
Tidskriftsartikel (refereegranskat)abstract
- Ichthyosaurs are extinct marine reptiles that display a notable external similarity to modern toothed whales. Here we show that this resemblance is more than skin deep. We apply a multidisciplinary experimental approach to characterize the cellular and molecular composition of integumental tissues in an exceptionally preserved specimen of the Early Jurassic ichthyosaur Stenopterygius. Our analyses recovered still-flexible remnants of the original scaleless skin, which comprises morphologically distinct epidermal and dermal layers. These are underlain by insulating blubber that would have augmented streamlining, buoyancy and homeothermy. Additionally, we identify endogenous proteinaceous and lipid constituents, together with keratinocytes and branched melanophores that contain eumelanin pigment. Distributional variation of melanophores across the body suggests countershading, possibly enhanced by physiological adjustments of colour to enable photoprotection, concealment and/or thermoregulation. Convergence of ichthyosaurs with extant marine amniotes thus extends to the ultrastructural and molecular levels, reflecting the omnipresent constraints of their shared adaptation to pelagic life.
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| 33. |
- Thunqvist, P., et al.
(författare)
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Lung Function at 8 and 16 Years After Moderate-to-Late Preterm Birth: A Prospective Cohort Study
- 2016
-
Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 137:4
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE: Knowledge regarding lung function after moderately preterm birth is limited. We therefore investigated lung function at early school age and adolescence among children born moderately preterm. METHODS: Data were used from the Swedish prospective birth cohort BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology study; N = 4089), with a 4.8% prevalence of moderate to late preterm birth defined as a gestational age of 32 to 36 weeks. Participants underwent spirometry at ages 8 and 16 years, and impulse oscillometry additionally at age 16 years. In total, 2621 children (149 preterm and 2472 term) provided lung function data. RESULTS: At age 8 years, adjusted forced expiratory volume in 1 second was lower in preterm female subjects (-64 mL [95% confidence interval (CI): -118 to -10]) compared with term female subjects but not in preterm male subjects. At age 16 years, both genders in the preterm group demonstrated lower forced expiratory volume in 1 second (female subjects: -116 mL [95% CI: -212 to -20]; male subjects: -177 mL [95% CI: -329 to -25]) compared with the term group. For the preterm group, impulse oscillometry demonstrated higher adjusted resistance at 5 Hz (female subjects: 31.3 Pa.L-1.s(-1) [95% CI: 6.3 to 56.3]; male subjects: 34.9 Pa.L-1.s(-1) [95% CI: 12.0 to 57.7]) and frequency dependence of resistance (resistance at 5 and 20 Hz) for male subjects (20.9 Pa.L-1.s(-1) [95% CI: 9.8 to 31.9]) compared with the term group. CONCLUSIONS: Measures of airway function assessed in adolescence were reduced in children born moderate to late preterm, and no catch-up in lung function between ages 8 and 16 years was observed.
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| 34. |
- Allansson, Elin, et al.
(författare)
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Overweight and obese children have lower cortisol levels than normal weight children
- 2014
-
Ingår i: Acta Paediatrica. - : Wiley-Blackwell. - 0803-5253 .- 1651-2227. ; 103:3, s. 295-299
-
Tidskriftsartikel (refereegranskat)abstract
- AIM: The stress hormone cortisol is vital to survival, and a disturbed circadian rhythm can be deleterious to health. However, little is known about cortisol levels in healthy children. The aim of this study was to examine cortisol levels in relation to body mass index (BMI), age and sex. METHODS: Salivary samples were collected in early morning, late morning and evening, on four consecutive days, from 342 children aged 6-12years using Salivette((R)) tubes. Samples were analysed using a commercial enzyme immunoassay (EIA). School nurses measured the children's height and weight, and these measurements were used to calculate their BMI. RESULTS: The children displayed a circadian rhythm in cortisol secretion, with morning zeniths and evening nadirs. Average cortisol levels in early morning, late morning and evening were significantly lower in overweight and obese children than in their normal weight counterparts. Cortisol levels did not vary significantly with age or sex. CONCLUSION: Our findings may suggest cortisol suppression in overweight and obese children. We found no evidence that sex or age influences cortisol levels. These findings highlight the need for further research on the relationship between stress and obesity in children.
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| 35. |
- Andre, M., et al.
(författare)
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Multi-spacecraft observations of broadband waves near the lower hybrid frequency at the Earthward edge of the magnetopause
- 2001
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Ingår i: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 19:12-okt, s. 1471-1481
-
Tidskriftsartikel (refereegranskat)abstract
- Broadband waves around the lower hybrid frequency (around 10 Hz) near the magnetopause are studied, using the four Cluster satellites. These waves are common at the Earthward edge of the boundary layer, consistent with earlier observations, and can have amplitudes at least up to 5 mV/m. These waves are similar on all four Cluster satellites, i.e. they are likely to be distributed over large areas of the boundary. The strongest electric fields occur during a few seconds, i.e. over distances of a few hundred km in the frame of the moving magnetopause, a scale length comparable to the ion gyroradius. The strongest magnetic oscillations in the same frequency range are typically found in the boundary layer, and across the magnetopause. During an event studied in detail, the magnetopause velocity is consistent with a large-scale depression wave, i.e. an inward bulge of magnetosheath plasma, moving tailward along the nominal magnetopause boundary. Preliminary investigations indicate that a rather flat front side of the large-scale wave is associated with a rather static small-scale electric field, while a more turbulent backside of the large-scale wave is associated with small-scale time varying electric field wave packets.
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| 36. |
- Bargholtz, Chr., et al.
(författare)
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Measurement of the eta -> pi(+)pi(-)e(+)e(-) decay branching ratio
- 2007
-
Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 644:5-6, s. 299-303
-
Tidskriftsartikel (refereegranskat)abstract
- The reaction pd -> He-3 eta at threshold was used to provide a clean source of eta mesons for decay studies with the WASA detector at CELSIUS. The branching ratio of the decay eta -> pi(+)pi(-)e(+)e(-) is measured to be (4.3 +/- 1.3 +/- 0.4) x 10(-4).
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| 37. |
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| 38. |
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| 39. |
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| 40. |
- Hallberg, J, et al.
(författare)
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Asthma phenotypes and lung function up to 16years of age-the BAMSE cohort.
- 2015
-
Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 70:6, s. 667-673
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Tidskriftsartikel (refereegranskat)abstract
- Asthma is a disease affecting many locations throughout the airway. Most studies have used spirometry as the primary assessment of airway obstruction, a method that may be less sensitive in regard to peripheral airway obstruction. The aim of this study was to elucidate the associations between asthma phenotypes based on age of onset and duration of symptoms, and (i) spirometry and (ii) small airway involvement measured by impulse oscillometry (IOS) in adolescence.
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| 41. |
- Ihre, E, et al.
(författare)
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Early rise in exhaled nitric oxide and mast cell activation in repeated low-dose allergen challenge
- 2006
-
Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 27:6, s. 1152-9
-
Tidskriftsartikel (refereegranskat)abstract
- Repeated low-dose allergen inhalation challenge mimics natural allergen exposure, providing a model for early mechanisms in the triggering of asthma. The current authors performed a controlled study to evaluate the time course of changes in exhaled nitric oxide fraction (F(e,NO)) and urinary biomarkers of airway inflammation. Eight subjects with mild allergic asthma completed two 7-day repeated low-dose challenge periods, with diluent and allergen, respectively. Subjects were symptom free at inclusion and were investigated when not exposed to specific allergen. Pulmonary function and symptoms were followed, and F(e,NO) and urinary mediators were correlated to changes in airway responsiveness to histamine and adenosine. Despite no change in pulmonary function (forced expiratory volume in one second mean+/-sem fall 0.3+/-0.7 versus 0.6+/-1.0%, for diluent and allergen, respectively) and no asthma symptoms, repeated allergen exposure, in contrast to diluent, caused significant increases in histamine responsiveness (2.3 doubling doses), an early and gradual increase in F(e,NO) (up to a doubling from baseline) and a small increase in the mast cell marker 9alpha11beta-prostaglandin F(2) after adenosine challenge. In conclusion, serial measurements of exhaled nitric oxide fraction have the potential to provide a very sensitive strategy for early detection of emerging airway inflammation and subsequent changes in airway hyperresponsiveness to histamine.
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| 42. |
- Kuliński, Karol, et al.
(författare)
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Biogeochemical functioning of the Baltic Sea
- 2022
-
Ingår i: Earth System Dynamics. - : Copernicus GmbH. - 2190-4979 .- 2190-4987. ; 13, s. 633-685
-
Forskningsöversikt (refereegranskat)abstract
- Location, specific topography, and hydrographic setting together with climate change and strong anthropogenic pressure are the main factors shaping the biogeochemical functioning and thus also the ecological status of the Baltic Sea. The recent decades have brought significant changes in the Baltic Sea. First, the rising nutrient loads from land in the second half of the 20th century led to eutrophication and spreading of hypoxic and anoxic areas, for which permanent stratification of the water column and limited ventilation of deep-water layers made favourable conditions. Since the 1980s the nutrient loads to the Baltic Sea have been continuously decreasing. This, however, has so far not resulted in significant improvements in oxygen availability in the deep regions, which has revealed a slow response time of the system to the reduction of the land-derived nutrient loads. Responsible for that is the low burial efficiency of phosphorus at anoxic conditions and its remobilization from sediments when conditions change from oxic to anoxic. This results in a stoichiometric excess of phosphorus available for organic-matter production, which promotes the growth of N2-fixing cyanobacteria and in turn supports eutrophication. This assessment reviews the available and published knowledge on the biogeochemical functioning of the Baltic Sea. In its content, the paper covers the aspects related to changes in carbon, nitrogen, and phosphorus (C, N, and P) external loads, their transformations in the coastal zone, changes in organic-matter production (eutrophication) and remineralization (oxygen availability), and the role of sediments in burial and turnover of C, N, and P. In addition to that, this paper focuses also on changes in the marine CO2 system, the structure and functioning of the microbial community, and the role of contaminants for biogeochemical processes. This comprehensive assessment allowed also for identifying knowledge gaps and future research needs in the field of marine biogeochemistry in the Baltic Sea. Copyright:
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| 43. |
- Nilsson, Anna, et al.
(författare)
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In Situ Mass Spectrometry Imaging and Ex Vivo Characterization of Renal Crystalline Deposits Induced in Multiple Preclinical Drug Toxicology Studies
- 2012
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10, s. e47353-
-
Tidskriftsartikel (refereegranskat)abstract
- Drug toxicity observed in animal studies during drug development accounts for the discontinuation of many drug candidates, with the kidney being a major site of tissue damage. Extensive investigations are often required to reveal the mechanisms underlying such toxicological events and in the case of crystalline deposits the chemical composition can be problematic to determine. In the present study, we have used mass spectrometry imaging combined with a set of advanced analytical techniques to characterize such crystalline deposits in situ. Two potential microsomal prostaglandin E synthase 1 inhibitors, with similar chemical structure, were administered to rats over a seven day period. This resulted in kidney damage with marked tubular degeneration/regeneration and crystal deposits within the tissue that was detected by histopathology. Results from direct tissue section analysis by matrix-assisted laser desorption ionization mass spectrometry imaging were combined with data obtained following manual crystal dissection analyzed by liquid chromatography mass spectrometry and nuclear magnetic resonance spectroscopy. The chemical composition of the crystal deposits was successfully identified as a common metabolite, bisulphonamide, of the two drug candidates. In addition, an un-targeted analysis revealed molecular changes in the kidney that were specifically associated with the area of the tissue defined as pathologically damaged. In the presented study, we show the usefulness of combining mass spectrometry imaging with an array of powerful analytical tools to solve complex toxicological problems occurring during drug development.
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| 44. |
- Nyholm, Tufve, et al.
(författare)
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A national approach for automated collection of standardized and population-based radiation therapy data in Sweden
- 2016
-
Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 119:2, s. 344-350
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To develop an infrastructure for structured and automated collection of interoperable radiation therapy (RT) data into a national clinical quality registry. Materials and methods: The present study was initiated in 2012 with the participation of seven of the 15 hospital departments delivering RT in Sweden. A national RT nomenclature and a database for structured unified storage of RT data at each site (Medical Information Quality Archive, MIQA) have been developed. Aggregated data from the MIQA databases are sent to a national RT registry located on the same IT platform (INCA) as the national clinical cancer registries. Results: The suggested naming convention has to date been integrated into the clinical workflow at 12 of 15 sites, and MIQA is installed at six of these. Involvement of the remaining 3/15 RT departments is ongoing, and they are expected to be part of the infrastructure by 2016. RT data collection from ARIA (R), Mosaiq (R), Eclipse (TM), and Oncentra (R) is supported. Manual curation of RT-structure information is needed for approximately 10% of target volumes, but rarely for normal tissue structures, demonstrating a good compliance to the RT nomenclature. Aggregated dose/volume descriptors are calculated based on the information in MIQA and sent to INCA using a dedicated service (MIQA2INCA). Correct linkage of data for each patient to the clinical cancer registries on the INCA platform is assured by the unique Swedish personal identity number. Conclusions: An infrastructure for structured and automated prospective collection of syntactically inter operable RT data into a national clinical quality registry for RT data is under implementation. Future developments include adapting MIQA to other treatment modalities (e.g. proton therapy and brachytherapy) and finding strategies to harmonize structure delineations. How the RT registry should comply with domain-specific ontologies such as the Radiation Oncology Ontology (ROO) is under discussion.
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| 45. |
- Schultz, E. S., et al.
(författare)
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Early life determinants of lung function change from childhood to adolescence
- 2018
-
Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 139, s. 48-54
-
Tidskriftsartikel (refereegranskat)abstract
- Rationale: Little is known about how perinatal and childhood factors influence lung function change between childhood and adolescence. Objectives: To investigate possible early life predictors of change in FEV1 between age 8 and 16 years. In addition, to investigate possible predictors of having persistently low lung function (FEV1 < 25th percentiles both at age 8 and 16) up to adolescence. Methods: The BAMSE birth cohort study collected data throughout childhood on environmental factors, individual characteristics, and spirometric measures at 8 and 16 years (n = 1425). Associations between early life predictors (n = 31) and FEV1 increase between 8 and 16 years were assessed with linear regression. Predictors of having persistently low lung function were examined. Results: Few factors were consistently associated with altered lung function growth, although low birth weight, asthma heredity (paternal), secondhand smoke in infancy, and season of birth had a significant impact (p-value <= 0.01). The majority of subjects stayed however within the same category of lung function between ages 8 and 16 years (in total 821/1425 = 58%). Predictors associated with having persistently low lung function were gestational age, secondhand smoke (at 2 and 8 years of age), and factors related to lower respiratory tract infections in infancy. Conclusions: In summary, rather few exposures in childhood were identified to have a significant impact on lung function growth between childhood and adolescence. Our data support previous study findings indicating that lung function development is influenced by factors before birth and in infancy, including second hand tobacco smoke.
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| 46. |
- Thacher, J. D., et al.
(författare)
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Tobacco smoke exposure in early life and adolescence in relation to lung function
- 2018
-
Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 51:6
-
Tidskriftsartikel (refereegranskat)abstract
- Maternal smoking during pregnancy is associated with impaired lung function among young children, but less is known about long-term effects and the impact of adolescents' own smoking. We investigated the influence of maternal smoking during pregnancy, secondhand smoke exposure and adolescent smoking on lung function at age 16 years. The BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology) birth cohort collected information on participants' tobacco smoke exposure through repeated questionnaires, and measured saliva cotinine concentrations at age 16 years. Participants performed spirometry and impulse oscillometry (IOS) at age 16 years (n=2295). Exposure to maternal smoking during pregnancy was associated with reduced forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio of -1.1% (95% CI -2.0 to -0.2%). IOS demonstrated greater resistance at 5-20 Hz (R5-20) in participants exposed to maternal smoking during pregnancy. Adolescents who smoked had reduced FEV1/FVC ratios of -0.9% (95% CI -1.8 to -0.1%) and increased resistance of 6.5 Pa.L-1.s (95% CI 0.7 to 12.2 Pa.L-1.s) in R5-20. Comparable associations for FEV1/FVC ratio were observed for cotinine concentrations, using. 12 ng.mL(-1) as a cut-off for adolescent smoking. Maternal smoking during pregnancy was associated with lower FEV1/FVC ratios and increased airway resistance. In addition, adolescent smoking appears to be associated with reduced FEV1/FVC ratios and increased peripheral airway resistance.
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| 47. |
- Agvald, Per, et al.
(författare)
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Increased expired NO and roles of CO2 and endogenous NO after venous gas embolism in rabbits
- 2006
-
Ingår i: European Journal of Applied Physiology. - Heidelberg, Germany : Springer Berlin/Heidelberg. - 1439-6319 .- 1439-6327. ; 97:2, s. 210-215
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Tidskriftsartikel (refereegranskat)abstract
- Venous gas embolism (VGE) is a feared complication in diving, aviation, surgery and trauma. We hypothesized that air emboli in the lung circulation might change expired nitric oxide (FeNO). A single intravenous infusion of air was given (100 mul kg(-1)) to three groups of anaesthetized mechanically ventilated rabbits: (A) one with intact NO production, (B) one with intact NO production and where end-tidal CO(2) was controlled, and (C) one with endogenous NO synthesis blockade (L: -NAME, 30 mg kg(-1)). Air infusions resulted in increased FeNO of the control group from 20 (4) [mean (SD)] ppb to a peak value of 39 (4) ppb within 5 min (P < 0.05), and FeNO was still significantly elevated [27 (2) ppb] after 20 min (P < 0.05). Parallel to the NO increase there were significant decreases in end-tidal CO(2 )(ETCO(2)) and mean arterial pressure and an increase in insufflation pressure. In group B, when CO(2) was supplemented after air infusion, NO was suppressed (P = 0.033), but was still significantly elevated compared with pre-infusion control (P < 0.05). In group C, all animals died within 40 min of air infusion whereas all animals in the other groups were still alive at this time point. We conclude that venous air embolization increases FeNO, and that a part of this effect is due to the concomitant decrease in ETCO(2). Furthermore, an intact NO production may be critical for the tolerance to VGE. Finally, FeNO might have a potential in the diagnosis and monitoring of pulmonary gas embolism.
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| 48. |
- Alling, Vanja, et al.
(författare)
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Non-conservative behavior of dissolved organic carbon across the Laptev and East Siberian Seas
- 2010
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Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 24, s. GB4033-
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Tidskriftsartikel (refereegranskat)abstract
- Climate change is expected to have a strong effect on the Eastern Siberian Arctic Shelf (ESAS) region, which includes 40% of the Arctic shelves and comprises the Laptev and East Siberian seas. The largest organic carbon pool, the dissolved organic carbon (DOC), may change significantly due to changes in both riverine inputs and transformation rates; however, the present DOC inventories and transformation patterns are poorly understood. Using samples from the International Siberian Shelf Study 2008, this study examines for the first time DOC removal in Arctic shelf waters with residence times that range from months to years. Removals of up to 10%–20% were found in the Lena River estuary, consistent with earlier studies in this area, where surface waters were shown to have a residence time of approximately 2 months. In contrast, the DOC concentrations showed a strong nonconservative pattern in areas with freshwater residence times of several years. The average losses of DOC were estimated to be 30%–50% during mixing along the shelf, corresponding to a first-order removal rate constant of 0.3 yr−1. These data provide the first observational evidence for losses of DOC in the Arctic shelf seas, and the calculated DOC deficit reflects DOC losses that are higher than recent model estimates for the region. Overall, a large proportion of riverine DOC is removed from the surface waters across the Arctic shelves. Such significant losses must be included in models of the carbon cycle for the Arctic Ocean, especially since the breakdown of terrestrial DOC to CO2 in Arctic shelf seas may constitute a positive feedback mechanism for Arctic climate warming. These data also provide a baseline for considering the effects of future changes in carbon fluxes, as the vast northern carbon-rich permafrost areas draining into the Arctic are affected by global warming.
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| 49. |
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| 50. |
- Amroussia, Nada, et al.
(författare)
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Do inequalities add up? : Intersectional inequalities in smoking by sexual orientation and education among U.S. adults
- 2020
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Ingår i: Preventive Medicine Reports. - : Elsevier. - 2211-3355. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Inequalities in smoking by socio-economic status (SES) are well-known. A growing body of literature has demonstrated additional inequalities in smoking by sexual orientation. This study used an intersectional lens to examine smoking at the intersection of sexual orientation and education.Methods: Data come from 28,362 adult participants in Wave 2 (2014–2015) of the Population Assessment of Tobacco and Health (PATH) Study. We used educational level (less than high school education (HS); HS or more) and sexual orientation (heterosexual; sexual minority) to form four intersectional positions.We estimated prevalence differences in smoking corresponding to joint, referent, and excess intersectional inequalities using weighted linear binomial regression models. Results were stratified by gender and adjusted for ethnicity and age.Results: The adjusted joint inequality represented 7.6% points (p.p.) (95% CI: 2.5, 12.8) difference in smoking between the doubly advantaged (heterosexual with HS or more) and doubly disadvantaged (sexual minority with less than HS) positions. Joint inequality was decomposed into referent SES inequality (12.5 p.p. (95% CI: 10.5, 14.4)); referent sexual orientation inequality (9.7 p.p. (95% CI: 6.8, 12.6)); and a substantial negative excess intersectional inequality (−14.6 p.p. (95% CI: −20.8, −8.3)), attributed to an unexpectedly low prevalence of smoking among doubly disadvantaged persons. Similar overall patterns were found in the stratified analyses.Conclusions: We found that “doubly-disadvantaged” group of low-educated sexual minority adults did not have the greatest burden of smoking; whereas, low-educated heterosexual adults had the highest smoking prevalence. Our findings support tailoring cessation interventions to disadvantaged groups’ different needs.
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