| 1. |
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| 2. |
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| 3. |
- Abe, K., et al.
(författare)
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J-PARC Neutrino Beamline Upgrade Technical Design Report
- 2019
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Rapport (refereegranskat)abstract
- In this document, technical details of the upgrade plan of the J-PARC neutrino beamline for the extension of the T2K experiment are described. T2K has proposed to accumulate data corresponding to 2×1022 protons-on-target in the next decade, aiming at an initial observation of CP violation with 3σ or higher significance in the case of maximal CP violation. Methods to increase the neutrino beam intensity, which are necessary to achieve the proposed data increase, are described.
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| 4. |
- Vogel, Jacob W., et al.
(författare)
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Four distinct trajectories of tau deposition identified in Alzheimer’s disease
- 2021
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 5. |
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| 6. |
- Edgecock, T. R., et al.
(författare)
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High intensity neutrino oscillation facilities in Europe
- 2013
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Ingår i: Physical Review Special Topics - Accelerators and Beams. - : American Physical Society. - 1098-4402. ; 16:2, s. 021002-
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Tidskriftsartikel (refereegranskat)abstract
- The EUROnu project has studied three possible options for future, high intensity neutrino oscillation facilities in Europe. The first is a Super Beam, in which the neutrinos come from the decay of pions created by bombarding targets with a 4 MW proton beam from the CERN High Power Superconducting Proton Linac. The far detector for this facility is the 500 kt MEMPHYS water Cherenkov, located in the Frejus tunnel. The second facility is the Neutrino Factory, in which the neutrinos come from the decay of mu(+) and mu(-) beams in a storage ring. The far detector in this case is a 100 kt magnetized iron neutrino detector at a baseline of 2000 km. The third option is a Beta Beam, in which the neutrinos come from the decay of beta emitting isotopes, in particular He-6 and Ne-18, also stored in a ring. The far detector is also the MEMPHYS detector in the Frejus tunnel. EUROnu has undertaken conceptual designs of these facilities and studied the performance of the detectors. Based on this, it has determined the physics reach of each facility, in particular for the measurement of CP violation in the lepton sector, and estimated the cost of construction. These have demonstrated that the best facility to build is the Neutrino Factory. However, if a powerful proton driver is constructed for another purpose or if the MEMPHYS detector is built for astroparticle physics, the Super Beam also becomes very attractive.
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| 7. |
- Underwood, J, et al.
(författare)
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Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment
- 2019
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Ingår i: Open forum infectious diseases. - : Oxford University Press (OUP). - 2328-8957. ; 6:6, s. ofz198-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts.MethodsDifferences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria.ResultsThe prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05).There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker.ConclusionDifferent methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach.
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| 8. |
- Zhou, XP, et al.
(författare)
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Non-coding variability at the APOE locus contributes to the Alzheimer's risk
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3310-
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.
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| 9. |
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| 10. |
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| 11. |
- Sanchez, Erlan, et al.
(författare)
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Association of plasma biomarkers with cognition, cognitive decline, and daily function across and within neurodegenerative diseases: Results from the Ontario Neurodegenerative Disease Research Initiative
- 2024
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Ingår i: Alzheimer's and Dementia. - 1552-5260 .- 1552-5279. ; 20:3, s. 1753-1770
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: We investigated whether novel plasma biomarkers are associated with cognition, cognitive decline, and functional independence in activities of daily living across and within neurodegenerative diseases. METHODS: Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (p-tau)181 and amyloid beta (Aβ)42/40 were measured using ultra-sensitive Simoa immunoassays in 44 healthy controls and 480 participants diagnosed with Alzheimer's disease/mild cognitive impairment (AD/MCI), Parkinson's disease (PD), frontotemporal dementia (FTD) spectrum disorders, or cerebrovascular disease (CVD). RESULTS: GFAP, NfL, and/or p-tau181 were elevated among all diseases compared to controls, and were broadly associated with worse baseline cognitive performance, greater cognitive decline, and/or lower functional independence. While GFAP, NfL, and p-tau181 were highly predictive across diseases, p-tau181 was more specific to the AD/MCI cohort. Sparse associations were found in the FTD and CVD cohorts and for Aβ42/40. DISCUSSION: GFAP, NfL, and p-tau181 are valuable predictors of cognition and function across common neurodegenerative diseases, and may be useful in specialized clinics and clinical trials.
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| 12. |
- Lieder, E O, et al.
(författare)
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Investigation of lifetimes in quadrupole bands of Gd-142
- 2008
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Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 35:2, s. 135-158
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Tidskriftsartikel (refereegranskat)abstract
- For a level scheme investigation of Gd-142 an experiment with the gamma -spectrometer EUROBALLIII has been carried out and lifetimes have been measured with EUROBALL IV using the Doppler-shift attenuation method. The high-spin states have been populated in these experiments by means of the(99)Ru(Ti-48, 2p3n) reaction at a beam energy of 240MeV and the Sn-114(S-32, 2p2n) reaction at 160MeV, respectively. Reduced E2 transition probabilities B(E2) were determined for 15 members of four quadrupole bands. For the interpretation of the positive-parity even-spin quadrupole bands, calculations in the cranked Nilsson-Strutinsky as well as interacting boson models have been performed. From the former calculations it was concluded that the high-spin states of the (+ , 0)(1) band in Gd-142 represent a triaxial nucleus rotating around the longest principal axis.
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| 13. |
- Masiteng, P. L., et al.
(författare)
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Close near-degeneracy in a pair of four-quasiparticle bands in Tl-194
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 83-88
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Tidskriftsartikel (refereegranskat)abstract
- A pair of rotational bands associated with the pi h(9/2) circle times nu i(13/2)(-1) configuration at lower spins and with the pi h(9/2) circle times nu i(13/2)(-3) configuration at higher spins is found in Tl-194. The two 4-quasiparticle bands show exceptionally close near-degeneracy in the excitation energies. Furthermore close similarity is also found in their alignments and B(M1)/B(E2) reduced transition probability ratios. Such close near-degeneracy probably indicates chiral geometry in the angular momentum space. (c) 2013 Elsevier B.V. All rights reserved.
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| 14. |
- Lieder, R. M., et al.
(författare)
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Investigations of the level scheme of Gd-144 and lifetimes in the quadrupole bands
- 2004
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 21:1, s. 37-55
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Tidskriftsartikel (refereegranskat)abstract
- For a level scheme investigation of Gd-144 an experiment with the gamma-spectrometer EUROBALL III has been carried out and lifetimes have been measured with the gamma-spectrometer GASP using the Doppler-shift attenuation method. The high-spin states have been populated in these experiments by means of the Mo-100(Ti-48,4n) reaction at 215 MeV and the Cd-114(S-36,6n) reaction at E = 182 MeV, respectively. The known quadrupole band has been modified and a new one has been established. Reduced E2 transition probabilities B(E2) were determined for seven members of these quadrupole bands. They show values between approximate to60 and 130 W.u. and this considerable enhancement gives evidence for a significant nuclear deformation. A (pih(11/2))(2) circle times (vh(11/2))(-2) configuration may be assigned to one of the quadrupole bands according to total Routhian surface calculations. The spin dependence of the B(E2) values has been explained by IBM calculations involving high-spin quasiparticle excitations.
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| 15. |
- Lieder, E. O., et al.
(författare)
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DSAM Lifetime Studies for Gd-Nd nuclei with EUROBALL and AFRODITE
- 2008
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Ingår i: Frontiers in Nuclear Structure, Astrophysics, and Reactions, FINUSTAR 2007. - : AIP. - 1551-7616 .- 0094-243X. - 9780735405325 ; 1012, s. 383-385
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Konferensbidrag (refereegranskat)abstract
- Lifetimes of high-spin states have been measured for 142Gd and 134Nd with EU-ROBALL IV and AFRODITE, respectively, using DSAM. From calculations in the cranked Nilsson-Strutinsky model it was concluded that at the high-spin states of the (+,0)1 band, 142Gd represents a triaxial nucleus rotating around the longest principal axis.
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| 16. |
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| 17. |
- Backes, Claudia, et al.
(författare)
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Production and processing of graphene and related materials
- 2020
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Ingår i: 2D Materials. - : IOP Publishing. - 2053-1583. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- We present an overview of the main techniques for production and processing of graphene and related materials (GRMs), as well as the key characterization procedures. We adopt a 'hands-on' approach, providing practical details and procedures as derived from literature as well as from the authors' experience, in order to enable the reader to reproduce the results. Section I is devoted to 'bottom up' approaches, whereby individual constituents are pieced together into more complex structures. We consider graphene nanoribbons (GNRs) produced either by solution processing or by on-surface synthesis in ultra high vacuum (UHV), as well carbon nanomembranes (CNM). Production of a variety of GNRs with tailored band gaps and edge shapes is now possible. CNMs can be tuned in terms of porosity, crystallinity and electronic behaviour. Section II covers 'top down' techniques. These rely on breaking down of a layered precursor, in the graphene case usually natural crystals like graphite or artificially synthesized materials, such as highly oriented pyrolythic graphite, monolayers or few layers (FL) flakes. The main focus of this section is on various exfoliation techniques in a liquid media, either intercalation or liquid phase exfoliation (LPE). The choice of precursor, exfoliation method, medium as well as the control of parameters such as time or temperature are crucial. A definite choice of parameters and conditions yields a particular material with specific properties that makes it more suitable for a targeted application. We cover protocols for the graphitic precursors to graphene oxide (GO). This is an important material for a range of applications in biomedicine, energy storage, nanocomposites, etc. Hummers' and modified Hummers' methods are used to make GO that subsequently can be reduced to obtain reduced graphene oxide (RGO) with a variety of strategies. GO flakes are also employed to prepare three-dimensional (3d) low density structures, such as sponges, foams, hydro- or aerogels. The assembly of flakes into 3d structures can provide improved mechanical properties. Aerogels with a highly open structure, with interconnected hierarchical pores, can enhance the accessibility to the whole surface area, as relevant for a number of applications, such as energy storage. The main recipes to yield graphite intercalation compounds (GICs) are also discussed. GICs are suitable precursors for covalent functionalization of graphene, but can also be used for the synthesis of uncharged graphene in solution. Degradation of the molecules intercalated in GICs can be triggered by high temperature treatment or microwave irradiation, creating a gas pressure surge in graphite and exfoliation. Electrochemical exfoliation by applying a voltage in an electrolyte to a graphite electrode can be tuned by varying precursors, electrolytes and potential. Graphite electrodes can be either negatively or positively intercalated to obtain GICs that are subsequently exfoliated. We also discuss the materials that can be amenable to exfoliation, by employing a theoretical data-mining approach. The exfoliation of LMs usually results in a heterogeneous dispersion of flakes with different lateral size and thickness. This is a critical bottleneck for applications, and hinders the full exploitation of GRMs produced by solution processing. The establishment of procedures to control the morphological properties of exfoliated GRMs, which also need to be industrially scalable, is one of the key needs. Section III deals with the processing of flakes. (Ultra)centrifugation techniques have thus far been the most investigated to sort GRMs following ultrasonication, shear mixing, ball milling, microfluidization, and wet-jet milling. It allows sorting by size and thickness. Inks formulated from GRM dispersions can be printed using a number of processes, from inkjet to screen printing. Each technique has specific rheological requirements, as well as geometrical constraints. The solvent choice is critical, not only for the GRM stability, but also in terms of optimizing printing on different substrates, such as glass, Si, plastic, paper, etc, all with different surface energies. Chemical modifications of such substrates is also a key step. Sections IV-VII are devoted to the growth of GRMs on various substrates and their processing after growth to place them on the surface of choice for specific applications. The substrate for graphene growth is a key determinant of the nature and quality of the resultant film. The lattice mismatch between graphene and substrate influences the resulting crystallinity. Growth on insulators, such as SiO2, typically results in films with small crystallites, whereas growth on the close-packed surfaces of metals yields highly crystalline films. Section IV outlines the growth of graphene on SiC substrates. This satisfies the requirements for electronic applications, with well-defined graphene-substrate interface, low trapped impurities and no need for transfer. It also allows graphene structures and devices to be measured directly on the growth substrate. The flatness of the substrate results in graphene with minimal strain and ripples on large areas, allowing spectroscopies and surface science to be performed. We also discuss the surface engineering by intercalation of the resulting graphene, its integration with Si-wafers and the production of nanostructures with the desired shape, with no need for patterning. Section V deals with chemical vapour deposition (CVD) onto various transition metals and on insulators. Growth on Ni results in graphitized polycrystalline films. While the thickness of these films can be optimized by controlling the deposition parameters, such as the type of hydrocarbon precursor and temperature, it is difficult to attain single layer graphene (SLG) across large areas, owing to the simultaneous nucleation/growth and solution/precipitation mechanisms. The differing characteristics of polycrystalline Ni films facilitate the growth of graphitic layers at different rates, resulting in regions with differing numbers of graphitic layers. High-quality films can be grown on Cu. Cu is available in a variety of shapes and forms, such as foils, bulks, foams, thin films on other materials and powders, making it attractive for industrial production of large area graphene films. The push to use CVD graphene in applications has also triggered a research line for the direct growth on insulators. The quality of the resulting films is lower than possible to date on metals, but enough, in terms of transmittance and resistivity, for many applications as described in section V. Transfer technologies are the focus of section VI. CVD synthesis of graphene on metals and bottom up molecular approaches require SLG to be transferred to the final target substrates. To have technological impact, the advances in production of high-quality large-area CVD graphene must be commensurate with those on transfer and placement on the final substrates. This is a prerequisite for most applications, such as touch panels, anticorrosion coatings, transparent electrodes and gas sensors etc. New strategies have improved the transferred graphene quality, making CVD graphene a feasible option for CMOS foundries. Methods based on complete etching of the metal substrate in suitable etchants, typically iron chloride, ammonium persulfate, or hydrogen chloride although reliable, are time- and resource-consuming, with damage to graphene and production of metal and etchant residues. Electrochemical delamination in a low-concentration aqueous solution is an alternative. In this case metallic substrates can be reused. Dry transfer is less detrimental for the SLG quality, enabling a deterministic transfer. There is a large range of layered materials (LMs) beyond graphite. Only few of them have been already exfoliated and fully characterized. Section VII deals with the growth of some of these materials. Amongst them, h-BN, transition metal tri- and di-chalcogenides are of paramount importance. The growth of h-BN is at present considered essential for the development of graphene in (opto) electronic applications, as h-BN is ideal as capping layer or substrate. The interesting optical and electronic properties of TMDs also require the development of scalable methods for their production. Large scale growth using chemical/physical vapour deposition or thermal assisted conversion has been thus far limited to a small set, such as h-BN or some TMDs. Heterostructures could also be directly grown. Section VIII discusses advances in GRM functionalization. A broad range of organic molecules can be anchored to the sp(2) basal plane by reductive functionalization. Negatively charged graphene can be prepared in liquid phase (e.g. via intercalation chemistry or electrochemically) and can react with electrophiles. This can be achieved both in dispersion or on substrate. The functional groups of GO can be further derivatized. Graphene can also be noncovalently functionalized, in particular with polycyclic aromatic hydrocarbons that assemble on the sp(2) carbon network by pi-pi stacking. In the liquid phase, this can enhance the colloidal stability of SLG/FLG. Approaches to achieve noncovalent on-substrate functionalization are also discussed, which can chemically dope graphene. Research efforts to derivatize CNMs are also summarized, as well as novel routes to selectively address defect sites. In dispersion, edges are the most dominant defects and can be covalently modified. This enhances colloidal stability without modifying the graphene basal plane. Basal plane point defects can also be modified, passivated and healed in ultra-high vacuum. The decoration of graphene with metal nanoparticles (NPs) has also received considerable attention, as it allows to exploit synergistic effects between NPs and graphene. Decoration can be either achieved chemically or in the gas phase. All LMs,
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| 18. |
- Carlsson, B. G., et al.
(författare)
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Triaxial shape with rotation around the longest principal axis in Gd-142
- 2008
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 78:3
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Tidskriftsartikel (refereegranskat)abstract
- The cranking model is used to describe rotational bands. We investigate the approach of using diabatic configurations and minimizing the particle-number projected energy in a mesh of both lambda, Delta and deformation parameters. We use the method to interpret recent experimental data in Gd-142 and conclude that for the highest spin states observed (I approximate to 30), the nucleus is triaxial and builds spin by rotating around the classically unfavored longest axis.
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| 19. |
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| 20. |
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| 21. |
- Engstrom, A., et al.
(författare)
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Sodium-Glucose Cotransporter 2 Inhibitor Treatment and Risk of Atrial Fibrillation: Scandinavian Cohort Study
- 2023
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 46:2, s. 351-360
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To assess the association between use of sodium-glucose cotransporter 2 (SGLT2) inhibitors and the risk of new-onset atrial fibrillation (AF) in routine clinical practice. RESEARCH DESIGN AND METHODS We used nationwide registers in Denmark, Norway, and Sweden from 2013 to 2018 in order to include patients without a history of AF who were newly prescribed an SGLT2 inhibitor or an active comparator (glucagon-like peptide 1 [GLP-1] receptor agonist). We performed a cohort study to assess new-onset AF in intention-to-treat analyses using Cox regression, adjusted for baseline covariates with propensity score weighting. RESULTS We identified 79,343 new users of SGLT2 inhibitors (59.2% dapagliflozin, 40.0% empagliflozin, 0.8% canagliflozin, <0.1% ertugliflozin) and 57,613 new users of GLP-1 receptor agonists. Mean age of the study cohort was 61 years and 60% were men. The adjusted incidence rate of new-onset AF was 8.6 per 1,000 person-years for new users of SGLT2 inhibitors compared with 10.0 per 1,000 person-years for new users of GLP-1 receptor agonists. The adjusted hazard ratio (aHR) was 0.89 (95% CI 0.81-0.96), and the rate difference was 1.4 fewer events per 1,000 person-years (95% CI 0.6-2.1). Using an as-treated exposure definition, the aHR for new-onset AF was 0.87 (95% CI 0.76-0.99). No statistically significant heterogeneity of the aHRs was observed between subgroups of patients with and without a history of heart failure or major cardiovascular disease. CONCLUSIONS In this cohort study using nationwide data from three countries, use of SGLT2 inhibitors, compared with GLP-1 receptor agonists, was associated with a modestly reduced risk of new-onset AF.
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| 22. |
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| 23. |
- Maccubbin, D., et al.
(författare)
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Lipid-modifying efficacy and tolerability of extended-release niacin/laropiprant in patients with primary hypercholesterolaemia or mixed dyslipidaemia
- 2008
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Ingår i: International journal of clinical practice (Esher). - : Hindawi Limited. - 1368-5031 .- 1742-1241. ; 62:12, s. 1959-1970
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Tidskriftsartikel (refereegranskat)abstract
- Background: Improving lipids beyond low-density lipoprotein cholesterol (LDL-C) lowering with statin monotherapy may further reduce cardiovascular risk. Niacin has complementary lipid-modifying efficacy to statins and cardiovascular benefit, but is underutilised because of flushing, mediated primarily by prostaglandin D2 (PGD2). Laropiprant (LRPT), a PGD 2 receptor (DP1) antagonist that reduces niacin-induced flushing has been combined with extended-release niacin (ERN) into a fixed-dose tablet. Methods and results: Dyslipidaemic patients were randomised to ERN/LRPT 1 g (n = 800), ERN 1 g (n = 543) or placebo (n = 270) for 4 weeks. Doses were doubled (2 tablets/day, i.e. 2 g for active treatments) for 20 weeks. ERN/LRPT 2 g produced significant changes vs. placebo in LDL-C (-18.4%), high-density lipoprotein cholesterol (HDL-C, 20.0%), LDL-C:HDL-C (-31.2%), non-HDL-C (-19.8%), triglycerides (TG, -25.8%), apolipoprotein (Apo) B (-18.8%), Apo A-I (6.9%), total cholesterol (TC, -8.5%), TC:HDL-C (-23.1%) and lipoprotein(a) (-20.8%) across weeks 12-24. ERN/LRPT produced significantly less flushing than ERN during initiation (week 1) and maintenance (weeks 2-24) for all prespecified flushing end-points (incidence, intensity and discontinuation because of flushing). Except for flushing, ERN/LRPT had a safety/tolerability profile comparable with ERN. Conclusion: Extended-release niacin/LRPT 2 g produced significant, durable improvements in multiple lipid/lipoprotein parameters. The improved tolerability of ERN/LRPT supports a simplified 1 g?2 g dosing regimen of niacin, a therapy proven to reduce cardiovascular risk. © 2008 Merck & Co.
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| 24. |
- Olli, Kalle, et al.
(författare)
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The fate of production in the central Arctic ocean - top-down regulation by zooplankton expatriates?
- 2007
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Ingår i: Progress in Oceanography. - : Elsevier BV. - 0079-6611 .- 1873-4472. ; 72:1, s. 84-113
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Forskningsöversikt (refereegranskat)abstract
- We estimated primary and bacterial production, mineral nutrients, suspended chlorophyll a (Chl), particulate organic carbon (POC) and nitrogen (PON), abundance of planktonic organisms, mesozooplankton fecal pellet production, and the vertical flux of organic particles of the central Arctic Ocean (Amundsen basin, 89 88° N) during a 3 week quasi-Lagrangian ice drift experiment at the peak of the productive season (August 2001). A visual estimate of ≈15% ice-free surface, plus numerous melt ponds on ice sheets, supported a planktonic particulate primary production of 50 150 mg C m‑2 d‑1 (mean 93 mg C m‑2 d‑1, n = 7), mostly confined to the upper 10 m of the nutrient replete water column. The surface mixed layer was separated from the rest of the water column by a strong halocline at 20 m depth. Phototrophic biomass was low, generally 0.03 0.3 mg Chl m‑3 in the upper 20 m and <0.02 mg Chl m‑3 below, dominated by various flagellates, dinoflagellates and diatoms. Bacterial abundance (typically 3.7 5.3 × 105, mean 4.1 × 105 cells ml‑1 in the upper 20 m and 1.3 3.7 × 105, mean 1.9 × 105 cells ml‑1 below) and Chl concentrations were closely correlated (r = 0.75). Mineral nutrients (3 μmol NO3 l‑1, 0.45 μmol PO4 l‑1, 4 5 μmol SiO4 l‑1) were probably not limiting the primary production in the upper layer. Suspended POC concentration was ˜30 105 (mean 53) mg C m‑3 and PON ˜5.4 14.9 (mean 8.2) mg N m‑3 with no clear vertical trend. The vertical flux of POC in the upper 30 100 m water column was ˜37 92 (mean 55) mg C m‑2 d‑1 without clear decrease with depth, and was quite similar at the six investigated stations. The mesozooplankton biomass (≈2 g DW m‑2, mostly in the upper 50 m water column) was dominated by adult females of the large calanoid copepods Calanus hyperboreus and Calanus glacialis (≈1.6 g DW m‑2). The grazing of these copepods (estimated via fecal pellet production rates) was ≈15 mg C m‑2 d‑1, being on the order of 3% and 20% of the expected food-saturated ingestion rates of C. hyperboreus and C. glacialis, respectively. The stage structure of these copepods, dominated by adult females, and their unsatisfied grazing capacity during peak productive period suggest allochthonous origin of these species from productive shelf areas, supported by their long life span and the prevailing surface currents in the Arctic Ocean. We propose that the grazing capacity of the expatriated mesozooplankton population would match the potential seasonal increase of primary production in the future decreased ice perspective, diminishing the likelihood of algal blooms.
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| 25. |
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| 26. |
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| 27. |
- Franken, T., et al.
(författare)
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Multi-objective optimization of water injection in spark-ignition engines using the stochastic reactor model with tabulated chemistry
- 2019
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Ingår i: International Journal of Engine Research. - : SAGE Publications. - 1468-0874 .- 2041-3149. ; 20:10, s. 1089-1100
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Tidskriftsartikel (refereegranskat)abstract
- Water injection is investigated for turbocharged spark-ignition engines to reduce knock probability and enable higher engine efficiency. The novel approach of this work is the development of a simulation-based optimization process combining the advantages of detailed chemistry, the stochastic reactor model and genetic optimization to assess water injection. The fast running quasi-dimensional stochastic reactor model with tabulated chemistry accounts for water effects on laminar flame speed and combustion chemistry. The stochastic reactor model is coupled with the Non-dominated Sorting Genetic Algorithm to find an optimum set of operating conditions for high engine efficiency. Subsequently, the feasibility of the simulation-based optimization process is tested for a three-dimensional computational fluid dynamic numerical test case. The newly proposed optimization method predicts a trade-off between fuel efficiency and low knock probability, which highlights the present target conflict for spark-ignition engine development. Overall, the optimization shows that water injection is beneficial to decrease fuel consumption and knock probability at the same time. The application of the fast running quasi-dimensional stochastic reactor model allows to run large optimization problems with low computational costs. The incorporation with the Non-dominated Sorting Genetic Algorithm shows a well-performing multi-objective optimization and an optimized set of engine operating parameters with water injection and high compression ratio is found.
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| 28. |
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| 29. |
- Ludvigsson, Jonas F., 1969-, et al.
(författare)
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Periconception glycaemic control in women with type 1 diabetes and risk of major birth defects: population based cohort study in Sweden
- 2018
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833 .- 0959-8138. ; 362
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To examine the association between maternal type 1 diabetes and the risk of major birth defects according to levels of glycated haemoglobin (HbA1C) within three months before or after estimated conception. Population based historical cohort study using nationwide health registers. 2458 singleton liveborn infants of mothers with type 1 diabetes and a glycated haemoglobin measurement within three months before or after estimated conception and 1 159 865 infants of mothers without diabetes. Major cardiac and non-cardiac birth defects according to glycated haemoglobin levels. 122 cases of major cardiac defects were observed among 2458 infants of mothers with type 1 diabetes. Compared with 15 cases of major cardiac defects per 1000 infants of mothers without diabetes, the rates among infants of mothers with type 1 diabetes were 33 per 1000 for a glycated haemoglobin level of <6.5% (adjusted risk ratio 2.17, 95% confidence interval 1.37 to 3.42), 49 per 1000 for 6.5% to <7.8% (3.17, 2.45 to 4.11), 44 per 1000 for 7.8% to <9.1% (2.79, 1.90 to 4.12), and 101 per 1000 for >= 9.1% (6.23, 4.32 to 9.00). The corresponding adjusted risk differences were 17 (5 to 36), 32 (21 to 46), 26 (13 to 46), and 77 (49 to 118) cases of major cardiac defects per 1000 infants, respectively. 50 cases of major non-cardiac defects were observed among infants of mothers with type 1 diabetes. Compared with 18 cases of major non-cardiac defects per 1000 infants of mothers without diabetes, the rates among infants of mothers with type 1 diabetes were 22 per 1000 for a glycated haemoglobin level of <6.5% (adjusted risk ratio 1.18, 0.68 to 2.07), 19 per 1000 for 6.5% to <7.8% (1.01, 0.66 to 1.54), 17 per 1000 for 7.8% to <9.1% (0.89, 0.46 to 1.69), and 32 per 1000 for >= 9.1%(1.68, 0.85 to 3.33). Among liveborn infants of mothers with type 1 diabetes, increasingly worse glycaemic control in the three months before or after estimated conception was associated with a progressively increased risk of major cardiac defects. Even with glycated haemoglobin within target levels recommended by guidelines (<6.5%), the risk of major cardiac defects was increased more than twofold. The risk of major non-cardiac defects was not statistically significantly increased at any of the four glycated haemoglobin levels examined; the study had limited statistical power for this outcome and was based on live births only.
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- Noh, Y, et al.
(författare)
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Prenatal and Infant Exposure to Acid-Suppressive Medications and Risk of Allergic Diseases in Children
- 2023
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Ingår i: JAMA pediatrics. - : American Medical Association (AMA). - 2168-6211 .- 2168-6203. ; 177:3, s. 267-277
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Tidskriftsartikel (refereegranskat)abstract
- Existing observational data have indicated positive associations of acid-suppressive medication (ASM) use in prenatal and early life with allergic diseases in children; however, no study to date has accounted for confounding by indication or within-familial factors.ObjectiveTo evaluate the association of prenatal or infant exposure to ASMs with risk of allergic diseases in children.Design, Setting, and ParticipantsThis nationwide, cohort study included data from South Korea’s National Health Insurance Service mother-child–linked database from January 1, 2007, to December 31, 2020. Participants included mother-child pairs of neonates born from April 1, 2008, to December 31, 2019.ExposuresPrenatal and infant exposure to ASMs (histamine 2 receptor antagonists [H2RAs] and proton pump inhibitors [PPIs]).Main Outcomes and MeasuresComposite and individual outcomes of allergic diseases (asthma, allergic rhinitis, atopic dermatitis, and food allergy) in children (followed up to 13 years of age) were assessed. The ASM-exposed individuals were compared with unexposed individuals in propensity score (PS)–matched and sibling-matched analyses to control for various potential confounders and within-familial factors. Hazard ratios (HRs) with 95% CIs were estimated using Cox proportional hazards regression models.ResultsThe study included 4 149 257 mother-child pairs. Prenatal exposure analyses included 808 067 PS-matched pairs (763 755 received H2RAs, 36 529 received PPIs) among women with a mean (SD) age of 31.8 (4.2) years. The PS-matched HR was 1.01 (95% CI, 1.01-1.02) for allergic diseases overall (asthma: HR, 1.02 [95% CI, 1.01-1.03]; allergic rhinitis: HR, 1.02 [95% CI, 1.01-1.02]; atopic dermatitis: HR, 1.02 [95% CI, 1.01-1.02]; food allergy: HR, 1.03 [95% CI, 0.98-1.07]); in sibling-matched analyses, the HRs were similar to those of PS-matched analyses but were not significant (allergic diseases: HR, 1.01; 95% CI, 0.997-1.01). Infant exposure analyses included 84 263 PS-matched pairs (74 188 received H2RAs, 7496 received PPIs). The PS-matched HR was 1.06 (95% CI, 1.05-1.07) for allergic diseases overall (asthma: HR, 1.16 [95% CI, 1.14-1.18]; allergic rhinitis: HR, 1.02 [95% CI, 1.01-1.03]; atopic dermatitis: HR, 1.05 [95% CI, 1.02-1.08]; food allergy: HR, 1.28 [95% CI, 1.10-1.49]); asthma risk (HR, 1.13; 95% CI, 1.09-1.17) remained significantly higher among children exposed to ASMs during infancy in sibling-matched analyses. The findings were similar for H2RAs and PPIs analyzed separately and were robust across all sensitivity analyses.Conclusions and RelevanceThe findings of this cohort study suggest that there is no association between prenatal exposure to ASMs and allergic diseases in offspring. However, infant exposure to ASMs was associated with a higher risk of developing asthma, although the magnitude was more modest than previously reported. Clinicians should carefully weigh the benefits of prescribing ASMs to children, accompanied by subsequent close monitoring for any clinically relevant safety signals.
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- Ueda, P., et al.
(författare)
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Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study
- 2018
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Ingår i: BMJ (Clinical research ed.). - : BMJ. - 1756-1833 .- 0959-8138. ; 363
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the association between the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and seven serious adverse events of current concern. DESIGN: Register based cohort study. SETTING: Sweden and Denmark from July 2013 to December 2016. PARTICIPANTS: A propensity score matched cohort of 17213 new users of SGLT2 inhibitors (dapagliflozin, 61%; empagliflozin, 38%; canagliflozin, 1%) and 17213 new users of the active comparator, glucagon-like peptide 1 (GLP1) receptor agonists. MAIN OUTCOME MEASURES: The primary outcomes were lower limb amputation, bone fracture, diabetic ketoacidosis, acute kidney injury, serious urinary tract infection, venous thromboembolism, and acute pancreatitis, as identified from hospital records. Hazard ratios and 95% confidence intervals were estimated by using Cox proportional hazards models. RESULTS: Use of SGLT2 inhibitors, as compared with GLP1 receptor agonists, was associated with an increased risk of lower limb amputation (incidence rate 2.7 v 1.1 events per 1000 person years, hazard ratio 2.32, 95% confidence interval 1.37 to 3.91) and diabetic ketoacidosis (1.3 v 0.6, 2.14, 1.01 to 4.52) but not with bone fracture (15.4 v 13.9, 1.11, 0.93 to 1.33), acute kidney injury (2.3 v 3.2, 0.69, 0.45 to 1.05), serious urinary tract infection (5.4 v 6.0, 0.89, 0.67 to 1.19), venous thromboembolism (4.2 v 4.1, 0.99, 0.71 to 1.38) or acute pancreatitis (1.3 v 1.2, 1.16, 0.64 to 2.12). CONCLUSIONS: In this analysis of nationwide registers from two countries, use of SGLT2 inhibitors, as compared with GLP1 receptor agonists, was associated with an increased risk of lower limb amputation and diabetic ketoacidosis, but not with other serious adverse events of current concern. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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| 39. |
- Ueda, P., et al.
(författare)
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The comparative cardiovascular and renal effectiveness of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists: A Scandinavian cohort study
- 2022
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Ingår i: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 24:3, s. 473-485
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Tidskriftsartikel (refereegranskat)abstract
- Aim To assess the comparative cardiovascular and renal effectiveness of sodium-glucose co-transporter-2 (SGLT2) inhibitors versus glucagon-like peptide-1 (GLP-1) receptor agonists in routine clinical practice. Materials and Methods A cohort study of nationwide registers from Sweden, Denmark, and Norway, including 87 525 new users of SGLT2 inhibitors and 63 921 new users of GLP-1 receptor agonists, was conducted using data from 2013-2018. Co-primary outcomes, analysed using an intention-to-treat exposure definition, were major adverse cardiovascular events (MACE; myocardial infarction, stroke, and cardiovascular death), heart failure (hospitalization or death because of heart failure), and serious renal events (renal replacement therapy, hospitalization for renal events, and death from renal causes). Results Use of SGLT2 inhibitors versus GLP-1 receptor agonists was associated with a higher risk of MACE (adjusted incidence rate: 15.2 vs. 14.4 events per 1000 person-years; HR 1.07 [95% CI 1.01-1.15]), a similar risk of heart failure (6.0 vs. 6.0 events per 1000 person-years; HR 1.02 [0.92-1.12]), and a lower risk of serious renal events (2.9 vs. 4.0 events per 1000 person-years; HR 0.76 [0.66-0.87]). In as-treated analyses, the HR (95% CI) was 1.11 (1.00-1.24) for MACE, 0.88 (0.74-1.04) for heart failure, and 0.60 (0.47-0.77) for serious renal events. In secondary outcome analyses, use of SGLT2 inhibitors versus GLP-1 receptor agonists was not associated with statistically significant differences for the risk of myocardial infarction (HR 1.09 [95% CI 1.00-1.19]), cardiovascular death (HR 0.97 [95% CI 0.84-1.12]), death from renal causes (HR 0.75 [95% CI 0.41-1.35]), or any cause death (HR 1.01 [95% CI 0.94-1.09]), while the risk of stroke was higher (HR 1.14 [95% CI 1.03-1.26]), and the risk of renal replacement therapy (HR 0.74 [95% CI 0.56-0.97]) and hospitalization for renal events (HR 0.75 [95% CI 0.65-0.88]) were lower among users of SGLT2 inhibitors. Conclusions Use of SGLT2 inhibitors versus GLP-1 receptor agonists was associated with a similar risk of heart failure and a lower risk of serious renal events, while use of GLP-1 receptor agonists versus SGLT2 inhibitors was associated with a slightly lower risk of MACE. In as-treated analyses, the associations with MACE and serious renal events increased in magnitude, and the HR for heart failure tended towards a protective association for SGLT2 inhibitors.
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