1. |
- Rydberg Sterner, Therese, et al.
(author)
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The Gothenburg H70 Birth cohort study 2014-16: design, methods and study population.
- 2019
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In: European journal of epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 34:2, s. 191-209
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Journal article (peer-reviewed)abstract
- To improve health care for older persons, we need to learn more about ageing, e.g. identify protective factors and early markers for diseases. The Gothenburg H70 Birth Cohort Studies (the H70 studies) are multidisciplinary epidemiological studies examining representative birth cohorts of older populations in Gothenburg, Sweden. So far, six birth cohorts of 70-year-olds have been examined over time, and examinations have been virtually identical between studies. This paper describes the study procedures for the baseline examination of the Birth cohort 1944, conducted in 2014-16. In this study, all men and women born 1944 on specific dates, and registered as residents in Gothenburg, were eligible for participation (n=1839). A total of 1203 (response rate 72.2%; 559 men and 644 women; mean age 70.5years) agreed to participate in the study. The study comprised sampling of blood and cerebrospinal fluid, psychiatric, cognitive, and physical health examinations, examinations of genetics and family history, use of medications, social factors, functional ability and disability, physical fitness and activity, body composition, lung function, audiological and ophthalmological examinations, diet, brain imaging, as well as a close informant interview, and qualitative studies. As in previous examinations, data collection serves as a basis for future longitudinal follow-up examinations. The research gained from the H70 studies has clinical relevance in relation to prevention, early diagnosis, clinical course, experience of illness, understanding pathogenesis and prognosis. Results will increase our understanding of ageing and inform service development, which may lead to enhanced quality of care for older persons.
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2. |
- Blomberg, Sara, et al.
(author)
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2D and 3D imaging of the gas phase close to an operating model catalyst by planar laser induced fluorescence
- 2016
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In: Journal of Physics: Condensed Matter. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 28:45
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Research review (peer-reviewed)abstract
- In recent years, efforts have been made in catalysis related surface science studies to explore the possibilities to perform experiments at conditions closer to those of a technical catalyst, in particular at increased pressures. Techniques such as high pressure scanning tunneling/atomic force microscopy (HPSTM/AFM), near ambient pressure x-ray photoemission spectroscopy (NAPXPS), surface x-ray diffraction (SXRD) and polarization-modulation infrared reflection absorption spectroscopy (PM-IRAS) at semi-realistic conditions have been used to study the surface structure of model catalysts under reaction conditions, combined with simultaneous mass spectrometry (MS). These studies have provided an increased understanding of the surface dynamics and the structure of the active phase of surfaces and nano particles as a reaction occurs, providing novel information on the structure/activity relationship. However, the surface structure detected during the reaction is sensitive to the composition of the gas phase close to the catalyst surface. Therefore, the catalytic activity of the sample itself will act as a gas-source or gas-sink, and will affect the surface structure, which in turn may complicate the assignment of the active phase. For this reason, we have applied planar laser induced fluorescence (PLIF) to the gas phase in the vicinity of an active model catalysts. Our measurements demonstrate that the gas composition differs significantly close to the catalyst and at the position of the MS, which indeed should have a profound effect on the surface structure. However, PLIF applied to catalytic reactions presents several beneficial properties in addition to investigate the effect of the catalyst on the effective gas composition close to the model catalyst. The high spatial and temporal resolution of PLIF provides a unique tool to visualize the on-set of catalytic reactions and to compare different model catalysts in the same reactive environment. The technique can be applied to a large number of molecules thanks to the technical development of lasers and detectors over the last decades, and is a complementary and visual alternative to traditional MS to be used in environments difficult to asses with MS. In this article we will review general considerations when performing PLIF experiments, our experimental set-up for PLIF and discuss relevant examples of PLIF applied to catalysis.
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3. |
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4. |
- Blomberg, Sara, et al.
(author)
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Combining synchrotron light with laser technology in catalysis research
- 2018
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In: Journal of Synchrotron Radiation. - 1600-5775 .- 0909-0495. ; 25:5, s. 1389-1394
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Journal article (peer-reviewed)abstract
- High-energy surface X-ray diffraction (HESXRD) provides surface structural information with high temporal resolution, facilitating the understanding of the surface dynamics and structure of the active phase of catalytic surfaces. The surface structure detected during the reaction is sensitive to the composition of the gas phase close to the catalyst surface, and the catalytic activity of the sample itself may affect the surface structure, which in turn may complicate the assignment of the active phase. For this reason, planar laser-induced fluorescence (PLIF) and HESXRD have been combined during the oxidation of CO over a Pd(100) crystal. PLIF complements the structural studies with an instantaneous two-dimensional image of the CO2 gas phase in the vicinity of the active model catalyst. Here the combined HESXRD and PLIF operandomeasurements of CO oxidation over Pd(100) are presented, allowing for an improved assignment of the correlation between sample structure and the CO2distribution above the sample surface with sub-second time resolution.
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5. |
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6. |
- Blomberg, Sara, et al.
(author)
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Real-Time Gas-Phase Imaging over a Pd(110) Catalyst during CO Oxidation by Means of Planar Laser-Induced Fluorescence.
- 2015
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In: ACS Catalysis. - : American Chemical Society (ACS). - 2155-5435. ; 5:4, s. 2028-2034
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Journal article (peer-reviewed)abstract
- The gas composition surrounding a catalytic sample has direct impact on its surface structure, which is essential when in situ investigations of model catalysts are performed. Herein a study of the gas phase close to a Pd(110) surface during CO oxidation under semirealistic conditions is presented. Images of the gas phase, provided by planar laser-induced fluorescence, clearly visualize the formation of a boundary layer with a significantly lower CO partial pressure close to the catalytically active surface, in comparison to the overall concentration as detected by mass spectrometry. The CO partial pressure variation within the boundary layer will have a profound effect on the catalysts' surface structure and function and needs to be taken into consideration for in situ model catalysis studies.
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7. |
- Blomberg, Sara, et al.
(author)
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Strain Dependent Light-off Temperature in Catalysis Revealed by Planar Laser-Induced Fluorescence
- 2017
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In: ACS Catalysis. - : American Chemical Society (ACS). - 2155-5435. ; 7:1, s. 110-114
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Journal article (peer-reviewed)abstract
- Understanding how specific atom sites on metal surfaces lower the energy barrier for chemical reactions is vital in catalysis. Studies on simplified model systems have shown that atoms arranged as steps on the surface play an important role in catalytic reactions, but a direct comparison of how the light-off temperature is affected by the atom orientation on the step has not yet been possible due to methodological constraints. Here we report in situ spatially resolved measurements of the CO2 production over a cylindrical-shaped Pd catalyst and show that the light-off temperature at different parts of the crystal depends on the step orientation of the two types of steps (named A and B). Our finding is supported by density functional theory calculations, revealing that the steps, in contrast to what has been previously reported in the literature, are not directly involved in the reaction onset but have the role of releasing stress.
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8. |
- Blomé, Mikael, et al.
(author)
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Course Supervision Challenges in PhD Education
- 2012
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In: 7:e Pedagogiska Inspirationskonferensen 2012. - 2003-3761 .- 2003-377X. ; 7
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Conference paper (peer-reviewed)abstract
- A large portion of the PhD education in Sweden is dedicated to courses. This made it interesting to explore potential course supervision challenges in the PhD programme. A multiple-case study was conducted to identify such challenges and explore how these are perceived by students and supervisors at the Faculty of Engineering of Lund University. By interviewing students and supervisors in five different research groups, insights were gained into how the main stakeholders reason about courses. The findings indicate that courses that are to be included in the education are characterized by a large degree of freedom tailored to individual student needs and preferences. However, the type, timing, availability, value, and convalidation of courses are challenges that limit this freedom.
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9. |
- Flodén, Jonas, 1974, et al.
(author)
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Shipping in the EU emissions trading system: implications for mitigation, costs and modal split
- 2024
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In: Climate Policy. - Stockholm : IVL Svenska Miljöinstitutet. - 1752-7457 .- 1469-3062. ; 24:7, s. 969-987
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Journal article (peer-reviewed)abstract
- EU recently decided to include shipping, meaning all intra-European shipping and 50% of extra-European voyages, in the EU Emissions Trading System (ETS) beginning in 2024. This article provides an early assessment of the impacts of the EU ETS on the shipping sector’s potential reductions in greenhouse gas emissions for different types of ships. It further examines selected mitigation measures and the impact on modals split and costs. The study employs a mixed-methods approach combining quantitative estimates (based on data from the EU monitoring, reporting and verification system) with qualitative data and information from interviews with key actors and from previous literature. This approach aims to provide a comprehensive understanding of the impacts of the EU ETS. The inclusion of shipping in the EU ETS is expected to introduce significant incentives to reduce emissions. We estimate that switching to bio-methanol at an emissions allowance price of €90–100/tCO2 will be cost-effective for a minor share of shipping segments (representing about 0.5-5% of all ships), whereas at a price above €150/tCO2 it could be cost-effective for a considerable share (potentially 75%) of ships. In the short term, the costs incurred by the EU ETS will be passed on to transport customers as a surcharge. The increased cost may, unless properly addressed, drive carbon leakage. Meanwhile, a modal shift away from shipping may occur in the roll-on, roll-off (RoRo) and roll-on passenger (RoPax) segments due to direct competition with road and rail transport and the relative ease of shifting to other modes of transport.
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10. |
- Fällmar, David, et al.
(author)
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The extent of neuroradiological findings in COVID-19 shows correlation with blood biomarkers, Glasgow coma scale score and days in intensive care
- 2022
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In: Journal of neuroradiology. - : Elsevier. - 0150-9861 .- 1773-0406. ; 49:6, s. 421-427
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Journal article (peer-reviewed)abstract
- Background and purposeA wide range of neuroradiological findings has been reported in patients with coronavirus disease 2019 (COVID-19), ranging from subcortical white matter changes to infarcts, haemorrhages and focal contrast media enhancement. These have been descriptively but inconsistently reported and correlations with clinical findings and biomarkers have been difficult to extract from the literature. The purpose of this study was to quantify the extents of neuroradiological findings in a cohort of patients with COVID-19 and neurological symptoms, and to investigate correlations with clinical findings, duration of intensive care and biomarkers in blood.Material and methodsPatients with positive SARS-CoV-2 and at least one new-onset neurological symptom were included from April until July 2020. Nineteen patients were examined regarding clinical symptoms, biomarkers in blood and MRI of the brain. In order to quantify the MRI findings, a semi-quantitative neuroradiological severity scale was constructed a priori, and applied to the MR images by two specialists in neuroradiology.Results and conclusionsThe score from the severity scale correlated significantly with blood biomarkers of CNS injury (glial fibrillary acidic protein, total-tau, ubiquitin carboxyl-terminal hydrolase L1) and inflammation (C-reactive protein), Glasgow Coma Scale score, and the number of days spent in intensive care. The underlying radiological assessments had inter-rater agreements of 90.5%/86% (for assessments with 2/3 alternatives). Total intraclass correlation was 0.80.Previously reported neuroradiological findings in COVID-19 have been diverse and heterogenous. In this study, the extent of findings in MRI examination of the brain, quantified using a structured report, shows correlation with relevant biomarkers.
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11. |
- Garcia-Martinez, Fernando, et al.
(author)
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Catalytic oxidation of CO on a curved Pt(111) surface : simultaneous ignition at all facets through a transient CO-O complex.
- 2020
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In: Angewandte Chemie International Edition. - : John Wiley & Sons. - 1433-7851 .- 1521-3773. ; 59:45, s. 20037-20043
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Journal article (peer-reviewed)abstract
- The catalytic oxidation of carbon monoxide (CO) on transition metals, such as platinum (Pt), is commonly viewed as a sharp transition from the CO-inhibited surface to the active metal, covered with oxygen (O). However, we find that minor amounts of O are present in the CO-poisoned layer that explain why, surprisingly, CO desorbs at stepped and flat Pt crystal planes at once, regardless of the reaction conditions. Using near-ambient pressure X-ray photoemission and a curved Pt(111) crystal we probe the chemical composition at surfaces with variable step density during the CO oxidation reaction. The systematic analysis of carbon and oxygen core levels across the curved crystal reveals that, right before light-off, subsurface O builds up within (111) terraces. This is key to trigger the simultaneous ignition of the catalytic reaction at different Pt surfaces, as indicated by ab-initio theory: a CO-Pt-O complex is formed that equals the CO chemisorption energy at terraces and steps, leading to the abrupt desorption of poisoning CO from all crystal facets at the same temperature.
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12. |
- Hansson, Julia, et al.
(author)
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Impact of including maritime transport in the EU ETS
- 2022
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Reports (other academic/artistic)abstract
- The European Green Deal from the European Commission in 2019 set a high aim: that EU will become climate neutral by 2050. As a part of this, the European Commission proposed that the EU Emission Trading System (ETS), is extended to include the maritime sector. This report assesses different design features of shipping in ETS, analyse the impact on the shipping industry and the environment. The report investigates what impacts the inclusion of shipping may have on incentives for abatement, what types of emission reductions may follow, if the policy will lead to modal shifts or carbon leakage (meaning that vessels avoid EU ports in order to evade the policy) and what attitudes and expectations can be found among Swedish shipping lines and transport customers.
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13. |
- Karlsson, Jan-Olof, 1944, et al.
(author)
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Inhibition of Glycogen Synthase Kinase (GSK-3) Protects Against Oxidative Stress and Attenuates Apoptosis in Human Lens Epithelial Cells and the Mouse Lens in Organ Culure
- 2005
-
In: Invest. Ophthalmol. Vis. Sci.. ; 46:5, s. 3867-
-
Conference paper (peer-reviewed)abstract
- Purpose: GSK-3 may regulate Wnt signaling, gene expression, the cell cycle, cell differentiation and apoptosis. Inhibition of GSK-3 can be obtained via the structurally unrelated substances lithum or Kenpaullone. The lens and the lens epithelial cells are excellent models to study the role of this enzyme. Methods: Primary cultures of human lens epithelial cells (HLEC) or the mouse lens in organ culture were exposed to the GSK-3 inhibitors lithium (2 mM) or Kenpaullone (2 {micro}M) for times upp to 24h.The cells were, before or after treatment, placed in medium containing fluorogenic indicators of oxidative damage. DCFH-DA was used to assay peroxides, mitochondrial function was evaluated with Rhodamine 123 and JC-1, monochlorobimane was used to assay intracellular glutathione (GSH) levels, Proteolytic activities were assayed, on line, with cell-permeable fluorogenic substrates.Proteasome and calpain activities were assayed with LLVY-AMC, Cathepsin B with RR-AMC or FR-AMC. Metalloproteases were assayed with AAF-AMC. Caspase-3, 8 and 9 were assayed in cell extracts with DEVD-, IETD- or LEHD-AMC, respectively. Results: The mitochondrial membrane potential and the level of GSH increased by 10% after treatment of HLEC with Li or Kenpaullone for 24h. No change was observed for peroxide production. The basal (low) level of caspase-3 activity was decreased by at least 20%. No significant effects were found concerning caspase-8 or 9 activities. No effect was observed on the activity of calpain, the proteasome, metalloproteases and cathepsin D/E activity.The whole mouse lens in organ culture showed essentially the same elevated mitochondrial potential. The GSH increase was even more evident in the whole lens preparation. Conclusions: Inhibition of GSK-3 may protect against oxidative stress (and cataract) via prevention of MPT induction and attenuate apoptosis in HLEC.
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14. |
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15. |
- Lundgren, Edvin, et al.
(author)
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Novel in Situ Techniques for Studies of Model Catalysts
- 2017
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In: Accounts of Chemical Research. - : American Chemical Society (ACS). - 0001-4842 .- 1520-4898. ; 50:9, s. 2326-2333
-
Journal article (peer-reviewed)abstract
- ConspectusMotivated mainly by catalysis, gas-surface interaction between single crystal surfaces and molecules has been studied for decades. Most of these studies have been performed in well-controlled environments and have been instrumental for the present day understanding of catalysis, providing information on surface structures, adsorption sites, and adsorption and desorption energies relevant for catalysis. However, the approach has been criticized for being too far from a catalyst operating under industrial conditions at high temperatures and pressures. To this end, a significant amount of effort over the years has been used to develop methods to investigate catalysts at more realistic conditions under operating conditions. One result from this effort is a vivid and sometimes heated discussion concerning the active phase for the seemingly simple CO oxidation reaction over the Pt-group metals in the literature.In recent years, we have explored the possibilities to perform experiments at conditions closer to those of a technical catalyst, in particular at increased pressures and temperatures. In this contribution, results from catalytic CO oxidation over a Pd(100) single crystal surface using Near Ambient Pressure X-ray Photo emission Spectroscopy (NAPXPS), Planar Laser-Induced Fluorescence (PLIF), and High Energy Surface X-ray Diffraction (HESXRD) are presented, and the strengths and weaknesses of the experimental techniques are discussed. Armed with structural knowledge from ultrahigh vacuum experiments, the presence of adsorbed molecules and gas-phase induced surface structures can be identified and related to changes in the reactivity or to reaction induced gas-flow limitations. In particular, the application of PLIF to catalysis allows one to visualize how the catalyst itself changes the gas composition close to the model catalyst surface upon ignition, and relate this to the observed surface structures. The effect obscures a straightforward relation between the active phase and the activity, since in the case of CO oxidation, the gas-phase close to the model catalyst surface is shown to be significantly more oxidizing than far away from the catalyst. We show that surface structural knowledge from UHV experiments and the composition of the gas phase close to the catalyst surface are crucial to understand structure-function relationships at semirealistic conditions. In the particular case of Pd, we argue that the surface structure of the PdO(101) has a significant influence on the activity, due to the presence of Coordinatively Unsaturated Sites (CUS) Pd atoms, similar to undercoordinated Ru and Ir atoms found for RuO2(110) and IrO2(110), respectively.
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16. |
- Matera, S., et al.
(author)
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Evidence for the Active Phase of Heterogeneous Catalysts through In Situ Reaction Product Imaging and Multiscale Modeling
- 2015
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In: ACS Catalysis. - : American Chemical Society (ACS). - 2155-5435. ; 5:8, s. 4514-4518
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Journal article (peer-reviewed)abstract
- We use multiscale modeling to analyze laser-induced fluorescence (LIP) measurements of the CO oxidation reaction over Pd(100) at near-ambient reaction conditions. Integrating density functional theory-based kinetic Monte Carlo simulations of the active catalyst into fluid-dynamical simulations of the mass transport inside the reactor chamber, we calculate the reaction product concentration directly above the catalyst surface. Comparing corresponding data calculated for different surface models against the measured LIP signals, we can discriminate the one that predominantly actuates the experimentally measured catalytic activity. For the probed CO oxidation reaction conditions, the experimental activity is due to pristine Pd(100) possibly coexisting with other (oxidic) domains on the surface.
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17. |
- Mehar, Vikram, et al.
(author)
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Formation of Epitaxial PdO(100) During the Oxidation of Pd(100)
- 2023
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In: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 14:38, s. 8493-8499
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Journal article (other academic/artistic)abstract
- The catalytic oxidation of CO and CH4 can be strongly influenced by the structures of oxide phases that form on metallic catalysts during reaction. Here, we show that an epitaxial PdO(100) structure forms at temperatures above 600 K during the oxidation of Pd(100) by gaseous O atoms as well as exposure to O2-rich mixtures at millibar partial pressures. The oxidation of Pd(100) by gaseous O atoms preferentially generates an epitaxial, multilayer PdO(101) structure at 500 K, but initiating Pd(100) oxidation above 600 K causes an epitaxial PdO(100) structure to grow concurrently with PdO(101) and produces a thicker and rougher oxide. We present evidence that this change in the oxidation behavior is caused by a temperature-induced change in the stability of small PdO domains that initiate oxidation. Our discovery of the epitaxial PdO(100) structure may be significant for developing relationships among oxide structure, catalytic activity, and reaction conditions for applications of oxidation catalysis.
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18. |
- Nilsson, Johanna, 1993, et al.
(author)
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Cerebrospinal fluid biomarker panel for synaptic dysfunction in Alzheimer's disease
- 2021
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In: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. - : Wiley. - 2352-8729. ; 13:1
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Journal article (peer-reviewed)abstract
- Introduction Synaptic dysfunction and degeneration is one of the earliest events in Alzheimer's disease (AD) and the best correlate of cognitive decline. Thus, identification and validation of biomarkers reflecting synaptic degeneration to be used as prognostic biomarkers are greatly needed. Method Solid-phase extraction and parallel reaction monitoring mass spectrometry were used to quantify 17 synaptic proteins in CSF, in two cross-sectional studies including AD (n = 52) and controls (n = 37). Results Increased concentrations of beta-synuclein, gamma-synuclein, neurogranin, phosphatidylethanolamine-binding protein 1, and 14-3-3 proteins were observed in AD patients compared to controls, while neuronal pentraxin-2 and neuronal pentraxin receptor were decreased. Discussion We have established a method with a novel panel of synaptic proteins as biomarkers of synaptic dysfunction. The results indicate that several of the proteins included in the panel may serve as synaptic biomarkers for AD.
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19. |
- Nogenmyr, Karl-Johan, et al.
(author)
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Large Eddy Simulation and Experiments of Stratified Lean Premixed Methane/Air Turbulent Flames
- 2007
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In: Proceedings of the Combustion Institute. - : Elsevier BV. - 1540-7489. ; 31:1, s. 1467-1475
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Journal article (peer-reviewed)abstract
- This paper presents a joint large eddy simulation and laser diagnostic investigation of premixed turbulent low swirl flames. A lean premixed methane/air mixture, of the equivalence ratio 0.60-0.66, is injected from a 50 mm diameter low swirl burner to a low speed co-flowing air at room temperature and pressure. The level-set G-equation is employed to simulate the inner layer flame front. Flamelet chemistry is used to determine the flame properties in the reactive zones. Mixing and heat transfer in the post-flame zone down-stream are modeled using transport equations. In addition to large eddy simulation, simultaneous 2-D laser induced fluorescence of OH and 2-D particle image velocimetry are used to characterize the basic flame structure. Laser Doppler velocimetry is employed to further analyze the flow velocity along the central axis above the burner, and 2-D filtered Rayleigh scattering is used to measure the temperature field in the lower part of the flame. A bowl-shaped, highly wrinkled turbulent flame is stabilized at a position about one-half diameter above the burner. The flame consists of two distinct parts; around the burner axis, a premixed flame with uniform mixture fraction is stabilized in the low speed flow region induced by the inflow swirl; off the axis of the burner, a stratified lean premixed flame is found in the shear layer of the flow field. Flame holes (local extinction) owing to overly lean mixtures are observed in the off-axis lean stratified part of the flame. A unified level-set G-equation is developed to model the flame holes. The basic flow and flame structure from the model simulations are compared to the laser diagnostic measurements; the height of flame stabilization (lift-off height), the mean temperature profile, and the mean axial and radial velocity components together with rms velocity components are in fairly good agreement with measurement data. © 2006 The Combustion Institute. Published by Elsevier Inc. All rights reserved.
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20. |
- Oliveira, Daniel V, et al.
(author)
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Active immunotherapy reduces NOTCH3 deposition in brain capillaries in a CADASIL mouse model.
- 2022
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In: EMBO molecular medicine. - : EMBO. - 1757-4684 .- 1757-4676. ; 15:2
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Journal article (peer-reviewed)abstract
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of familial small vessel disease; no preventive or curative therapy is available. CADASIL is caused by mutations in the NOTCH3 gene, resulting in a mutated NOTCH3 receptor, with aggregation of the NOTCH3 extracellular domain (ECD) around vascular smooth muscle cells. In this study, we have developed a novel active immunization therapy specifically targeting CADASIL-like aggregated NOTCH3 ECD. Immunizing CADASIL TgN3R182C150 mice with aggregates composed of CADASIL-R133C mutated and wild-type EGF1-5 repeats for a total of 4months resulted in a marked reduction (38-48%) in NOTCH3 deposition around brain capillaries, increased microglia activation and lowered serum levels of NOTCH3 ECD. Active immunization did not impact body weight, general behavior, the number and integrity of vascular smooth muscle cells in the retina, neuronal survival, or inflammation or the renal system, suggesting that the therapy is tolerable. This is the first therapeutic study reporting a successful reduction of NOTCH3 accumulation in a CADASIL mouse model supporting further development towards clinical application for the benefit of CADASIL patients.
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21. |
- Pannee, Josef, 1979, et al.
(author)
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The amyloid-beta degradation pattern in plasma A possible tool for clinical trials in Alzheimer's disease
- 2014
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In: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 573, s. 7-12
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Journal article (peer-reviewed)abstract
- Amyloid beta (A beta) is the main component of plaques, the central neuropathological hallmark in Alzheimer's disease (AD). A beta is derived from the amyloid precursor protein (APP) by beta- and gamma-secretase-mediated cleavages. A large number of A beta peptides are found in cerebrospinal fluid and these peptides are produced in specific metabolic pathways, which are important for diagnosis, in drug development and to explore disease pathogenesis. To investigate whether a similar pattern could be found also in blood samples, an immunoprecipitation (IP) based method for enrichment of A beta peptides from human plasma was developed. The peptides were analyzed using matrix-assisted-laser-desorption/ionization time-of-flight/time-of-flight mass spectrometry for A beta profiling and selected reaction monitoring (SRM) for MS quantification of A beta 1-38, A beta 1-40 and A beta 1-42 using tripe quadrupole MS. Sixteen N- or C-terminally truncated A beta peptides were reproducibly detected in human plasma, of which 11 were verified by tandem MS. In a pilot study including 9 AD patients and 10 controls, where A beta 1-38, A beta 1-40 and A beta 1-42 were quantified using SRM, no AD-associated change in plasma levels of the peptides were observed. Using MS-based measurement techniques, we show that several A beta peptides can be monitored in a single analysis and the developed methods have the potential to be used as a read out in clinical trials of drugs affecting APP processing or A beta homeostasis.
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22. |
- Petersen, Anne, 1962, et al.
(author)
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The Mechanism of Antioxidant Actions by NSAIDs/ASA in Cultured Human Lens Epithelial Cells
- 2005
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In: Invest. Ophthalmol. Vis. Sci.. ; 46:5, s. 3854-
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Conference paper (peer-reviewed)abstract
- Purpose: To study the possible mechanisms for protection against oxidative stress by indomethacin, diclofenac, celecoxib (NSAIDs) or acetylsalicylic acid (ASA) in cultured human lens epithelial cells (HLEC). Methods: Changes in peroxide levels in HLEC was measured after exposure to low concentrations (0, 0.005, 0.05 or 0,5 {micro}M) of indomethacin, diclofenac, celecoxib or acetylsalicylic acid for 24 hours. The cells were assayed at regular intervals during 24 h using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). Cultured HLEC were incubated with H2O2 (200 {micro}M) alone or in the presence of NSAIDs/ASA. The cells were then assayed for changes in GSH levels using monochlorobimane (MCB). Results: NSAIDs/ASA at concentrations previous described to be effective against oxidative stress in HLEC did not affect peroxide levels in cultured HLEC. The reducing capacity as measured as the GSH levels, were not significantly changed in oxidatively stressed HLEC. No toxic effects on GSH or peroxide levels were present. Conclusions: Indomethacin, diclofenac, celecoxib or acetylsalicylic acid does not exert their protective actions against oxidative stress via changed levels of endogenous peroxide or GSH.
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23. |
- Shahim, Pashtun, et al.
(author)
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Cerebrospinal Fluid Brain Injury Biomarkers in Children: A Multicenter Study
- 2013
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In: Pediatric Neurology. - : Elsevier BV. - 0887-8994 .- 1873-5150. ; 80
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Journal article (peer-reviewed)abstract
- BACKGROUND: Cerebrospinal fluid (CSF) biomarkers reflecting neuronal and astroglial injury, such as total tau (T-tau), glial flbrillary acidic protein (GFAP), and neurofilament light (NFL), have been extensively investigated in neurologic diseases in adults, but no large study has investigated these biomarkers in children. METHODS: This study presents a detailed evaluation of CFS T-tau, GFAP, NFL, and CSF:albumin ratio in a large cohort of pediatric patients. This is a retrospective multicenter study on pediatric patients aged <16 years (n = 607), where neuronal injury biomarkers T-tau, GFAP, NFL, and CSF albumin ratio were analyzed during 2000-2010 at the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Sweden. The patients were grouped into eight categories: epilepsy, infectious and inflammatory central nervous system disorders, progressive encephalopathy, static encephalopathy, tumors, movement disorders, miscellaneous disorders, and a control group. RESULTS: T-tau, GFAP, and NFL were increased in progressive encephalopathy (P < 0.001), epilepsy (P < 0.001), and infectious and inflammatory central nervous system disorders (P < 0.001) compared with controls. T-tau was the biomarker with the highest diagnostic accuracy with the area under the curve of 0.83 (95% confidence interval (CI), 0.77-0.90; P < 0.0001) for progressive encephalopathy followed by epilepsy 0.80 (95% CI, 0.75-0.87; P < 0.0001). The combination of all four biomarkers further improved the area under the curve for the progressive encephalopathy 0.87 (95% CI, 0.77-0.89; P < 0.0001), followed by epilepsy 0.81 (95% CI, 0.74-0.80; P = 0.030). The combination of the biomarkers also separated progressive from static encephalopathy 0.88 (95% CI, 0.83-0.93; P < 0.0001). CONCLUSIONS: CSF T-tau, GFAP, and NFL are differently altered across different neurologic diseases in children. Importantly, the biomarker pattern distinguishes between progressive and static neurologic disorders. (c) 2013 Elsevier Inc. All rights reserved.
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24. |
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25. |
- Ursberg, Johan, et al.
(author)
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Phacoemulsification practices: A comprehensive analysis of the surgical landscape in Sweden 2021-2022
- 2024
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In: ACTA OPHTHALMOLOGICA. - : John Wiley & Sons. - 1755-375X .- 1755-3768.
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Journal article (peer-reviewed)abstract
- PurposeThis cross-sectional survey study aimed to explore the phacoemulsification techniques among Swedish cataract surgeons, and investigate the association between technique preferences and surgical outcomes, particularly posterior capsular rupture (PCR).MethodsA survey questionnaire was responded by 170 cataract surgeons and data from 192 494 cases, linked to the surgeons, were analysed from the Swedish National Cataract Registry (SNCR) for 2021-2022. Surgeons' demographic characteristics, surgical techniques and complications were assessed. Associations between surgical technique preferences and outcomes were analysed with binary logistic regression.ResultsThe chopping technique (stop and chop or direct chop) was favoured by 64.6% of surgeons, followed by divide and conquer (32.4%), and tilt and tumble (7.6%). Surgeons' annual caseloads varied widely (range 11-2687). No significant correlation was found between technique preference and PCR rates, which was consistently 0.5%-0.6% in all groups, except for a trend suggesting reduced risk with tilt and tumble. Mentoring activity (35.0%) and public surgical setting (40.3%) was highest in the direct chop group. Notably, 75% of the surgeries were performed by surgeons with more than 10 years' experience. Confounding factors, such as high-volume surgeons having a low frequency of complications, have been accounted for in a logistic regression.ConclusionThis study provides insights into cataract surgery practices in Sweden and suggests that surgeons can choose their preferred approach without significantly affecting complication rates. This research also underscores the need for continued exploration of surgical practices and their impact on patient outcomes, particularly in the case of the tilt and tumble technique, which is less commonly employed.
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26. |
- Virhammar, Johan, et al.
(author)
-
Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid
- 2020
-
In: Neurology. - 0028-3878 .- 1526-632X. ; 95:10, s. 445-449
-
Journal article (peer-reviewed)abstract
- Here, we report a case of COVID-19–related acute necrotizing encephalopathy where SARS-CoV-2 RNA was found in CSF 19 days after symptom onset after testing negative twice. Although monocytes and protein levels in CSF were only marginally increased, and our patient never experienced a hyperinflammatory state, her neurologic function deteriorated into coma. MRI of the brain showed pathologic signal symmetrically in central thalami, subinsular regions, medial temporal lobes, and brain stem. Extremely high concentrations of the neuronal injury markers neurofilament light and tau, as well as an astrocytic activation marker, glial fibrillary acidic protein, were measured in CSF. Neuronal rescue proteins and other pathways were elevated in the in-depth proteomics analysis. The patient received IV immunoglobulins and plasma exchange. Her neurologic status improved, and she was extubated 4 weeks after symptom onset. This case report highlights the neurotropism of SARS-CoV-2 in selected patients and emphasizes the importance of repeated lumbar punctures and CSF analyses in patients with suspected COVID-19 and neurologic symptoms.
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27. |
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28. |
- Wallerius, Johan Gottschalk, 1709-1785
(author)
-
Dissertatio physico mineralogica, de vegetatione mineralium, qvam, suffragio ampliss. facult. philosoph. in regia academia Upsaliensi, præside, viro amplissimo atque celeberrimo d:n Joh. Gotschalk Wallerio, ... publico examini submittit, Wilh. Gust. Zetterberg, Sudermannus. In audit. Gustaviano ad d. XXVI. Maji. anni MDCCLXIII. Horis ante meridiem solitis.
- 1763
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Doctoral thesis (other academic/artistic)
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29. |
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30. |
- Wang, Hao, 1975, et al.
(author)
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Genome-scale metabolic network reconstruction of model animals as a platform for translational research
- 2021
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:30
-
Journal article (peer-reviewed)abstract
- Genome-scale metabolic models (GEMs) are used extensively for analysis of mechanisms underlying human diseases and metabolic malfunctions. However, the lack of comprehensive and high-quality GEMs for model organisms restricts translational utilization of omics data accumulating from the use of various disease models. Here we present a unified platform of GEMs that covers five major model animals, including Mouse1 (Mus musculus), Rat1 (Rattus norvegicus), Zebrafish1 (Danio rerio), Fruitfly1 (Drosophila melanogaster), and Worm1 (Caenorhabditis elegans). These GEMs represent the most comprehensive coverage of the metabolic network by considering both orthology-based pathways and species-specific reactions. All GEMs can be interactively queried via the accompanying web portal Metabolic Atlas. Specifically, through integrative analysis of Mouse1 with RNA-sequencing data from brain tissues of transgenic mice we identified a coordinated up-regulation of lysosomal GM2 ganglioside and peptide degradation pathways which appears to be a signature metabolic alteration in Alzheimer’s disease (AD) mouse models with a phenotype of amyloid precursor protein overexpression. This metabolic shift was further validated with proteomics data from transgenic mice and cerebrospinal fluid samples from human patients. The elevated lysosomal enzymes thus hold potential to be used as a biomarker for early diagnosis of AD. Taken together, we foresee that this evolving open-source platform will serve as an important resource to facilitate the development of systems medicines and translational biomedical applications.
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31. |
- Wejryd, Johan, 1978-
(author)
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On Consumed Democracy : The Expansion of Consumer Choice, Its Causal Effects on Political Engagement, and Its Implications for Democracy
- 2018
-
Doctoral thesis (other academic/artistic)abstract
- This is a thesis about expansions of consumer choice, their causal effects on political engagement, and the democratic implications that follow. For material and ideological reasons alike, consumer choices have expanded over the last decades and are likely to become even more present in citizens’ lives in the future. Scholars’ appraisal of this expansion of consumer choice ranges from, on the one hand, seeing it as a threat to active citizenship to, on the other hand, celebrating it as inherently democratic.The thesis accepts the assumed democratic potential of consumer choice as a means for conveying legitimate political preferences and affecting political outcomes. Yet the introduction shows that, from the perspective of normative democratic theory, citizens’ consumer choices are under most circumstances democratically inferior to civic engagement that addresses formal political decision-making. It is thus a pressing question whether there actually are elements in consumer choices that reduce citizens’ inclination to engage in conventional forms of political participation. This empirical question is addressed in the three essays.The essays tap the effects of consumer choices in different contexts, such as parents’ school choices for their children (Essay I), consumer choices that interact with citizens’ political motivations, i.e. “political consumption,” (Essay II), and consumer choices regarding plainly private consumer goods (Essay III). All the three essays account for causality and do so by means of experimental designs. In addition, the essays are similar in that their results point in the same direction: expansions of consumer choice reduce citizens’ willingness to conventional political participation.Given the democratic significance of conventional participation and the pervasiveness of consumer choice, the results are important both from a scholarly perspective and from a broader societal perspective. The results cast new light on a wide range of issues about the extension of consumer choices and their presence in citizens’ lives, including e.g. decisions about user choice in welfare services and advertising regulation. This thesis does by no means end the discussion about such policies, but demonstrates the significance of a certain outlook: issues about the extension of consumer choice are issues about democratic values.
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32. |
- Zetterberg, Johan, et al.
(author)
-
An in situ set up for the detection of CO(2) from catalytic CO oxidation by using planar laser-induced fluorescence.
- 2012
-
In: Review of Scientific Instruments. - : AIP Publishing. - 1089-7623 .- 0034-6748. ; 83:5
-
Journal article (peer-reviewed)abstract
- We report the first experiment carried out on an in situ setup, which allows for detection of CO(2) from catalytic CO oxidation close to a model catalyst under realistic reaction conditions by the means of planar laser-induced fluorescence (PLIF) in the mid-infrared spectral range. The onset of the catalytic reaction as a function of temperature was followed by PLIF in a steady state flow reactor. After taking into account the self-absorption of CO(2), a good agreement between the detected CO(2) fluorescence signal and the CO(2) mass spectrometry signal was shown. The observed difference to previously measured onset temperatures for the catalytic ignition is discussed and the potential impact of IR-PLIF as a detection technique in catalysis is outlined.
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33. |
- Zetterberg, Johan, et al.
(author)
-
Planar laser induced fluorescence applied to catalysis
- 2017
-
In: Springer Series in Chemical Physics. - Cham : Springer International Publishing. - 0172-6218. ; 114, s. 131-149
-
Book chapter (peer-reviewed)abstract
- In this chapter we describe Planar Laser Induced Fluorescence (PLIF) to investigate the reactants or products in the vicinity of a catalyst at semi-realistic conditions. PLIF provides a 2D view of the gas-phase distribution of a pre-chosen gas. Here we present PLIF results from CO2 and CO from the oxidation of CO into CO2 by Pd single crystals and by various powder catalysts as well as from NH3 from the oxidation of NH3 above a Ag/Al2O3 powder catalyst.We describe our experimental set-up in detail, and the laser instrumentation needed to enable detectable gas fluorescence from CO2, CO, and NH3, respectively. Further, intensity corrections of the PLIF signal due to scattering and temperature effects are described. In the case of the CO oxidation, the results directly show the creation of a CO2 boundary layer and thus a drastic change of the gas-phase composition close to the catalyst surface, illustrating the effect of gas diffusion and reaction speed, which in turn should affect the surface structure of the active catalyst. The 2D character of the PLIF images is used to investigate differences in catalyst activity by studying adjacent catalysts in the reaction cell during the reaction, and a solution to avoid spill-over effects between catalysts in the same reactor is presented. The results from PLIF images of CO of the same reaction show the corresponding depletion of the PLIF intensity above the catalyst, in accordance with observations from other techniques confirming the drastic difference between the gas composition close to the catalyst and at the inlet or outlet of the reactor. Finally we present NH3 PLIF results from above a Ag/Al2O3 powder catalyst while the NH3 is being oxidized in an oxidizing environment with the assistance of H2.
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34. |
- Zetterberg, Johan, et al.
(author)
-
Spatially and temporally resolved gas distributions around heterogeneous catalysts using infrared planar laser-induced fluorescence.
- 2015
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
-
Journal article (peer-reviewed)abstract
- Visualizing and measuring the gas distribution in close proximity to a working catalyst is crucial for understanding how the catalytic activity depends on the structure of the catalyst. However, existing methods are not able to fully determine the gas distribution during a catalytic process. Here we report on how the distribution of a gas during a catalytic reaction can be imaged in situ with high spatial (400 μm) and temporal (15 μs) resolution using infrared planar laser-induced fluorescence. The technique is demonstrated by monitoring, in real-time, the distribution of carbon dioxide during catalytic oxidation of carbon monoxide above powder catalysts. Furthermore, we demonstrate the versatility and potential of the technique in catalysis research by providing a proof-of-principle demonstration of how the activity of several catalysts can be measured simultaneously, either in the same reactor chamber, or in parallel, in different reactor tubes.
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35. |
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36. |
- Zhou, Jianfeng, et al.
(author)
-
Simultaneous Imaging of Gas Phase over and Surface Reflectance of a Pd(100) Single Crystal during CO Oxidation
- 2017
-
In: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 121:42, s. 23511-23519
-
Journal article (peer-reviewed)abstract
- A direct correlation between the reaction activity and the surface structure of a catalyst is generally needed to better understand the mechanisms behind the heterogeneous catalysis process. In this work, we employed planar laser-induced fluorescence (PLIF) to spatially resolve the CO2 distribution just above a Pd(100) surface, and simultaneously monitored the optical reflectance of the surface, during CO oxidation. We show that when the reaction is in the mass transfer limited regime, the inhomogeneity of the gas composition over the sample can lead to an inhomogeneity of the surface reflectance change arising from oxide formation and surface roughening. The combination of PLIF and surface reflectance also makes it possible to spatially resolve and simultaneously follow the dynamics of the gas phase and the surface on a subsecond time scale during self-sustained reaction oscillations of a Pd(100) surface, providing insights into the gas-surface interaction.
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37. |
- Zhou, Jianfeng, et al.
(author)
-
Visualization of gas distribution in a model AP-XPS reactor by PLIF : Co oxidation over a Pd(100) catalyst
- 2017
-
In: Catalysts. - : MDPI AG. - 2073-4344. ; 7:1
-
Journal article (peer-reviewed)abstract
- In situ knowledge of the gas phase around a catalyst is essential to make an accurate correlation between the catalytic activity and surface structure in operando studies. Although ambient pressure X-ray photoelectron spectroscopy (AP-XPS) can provide information on the gas phase as well as the surface structure of a working catalyst, the gas phase detected has not been spatially resolved to date, thus possibly making it ambiguous to interpret the AP-XPS spectra. In this work, planar laser-induced fluorescence (PLIF) is used to visualize the CO2 distribution in a model AP-XPS reactor, during CO oxidation over a Pd(100) catalyst. The results show that the gas composition in the vicinity of the sample measured by PLIF is significantly different from that measured by a conventional mass spectrometer connected to a nozzle positioned just above the sample. In addition, the gas distribution above the catalytic sample has a strong dependence on the gas flow and total chamber pressure. The technique presented has the potential to increase our knowledge of the gas phase in AP-XPS, as well as to optimize the design and operating conditions of in situ AP-XPS reactors for catalysis studies.
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38. |
- Abb, Marcel J.S., et al.
(author)
-
Thermal Stability of Single-Crystalline IrO2(110) Layers : Spectroscopic and Adsorption Studies
- 2020
-
In: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 124:28, s. 15324-15336
-
Journal article (peer-reviewed)abstract
- The interaction of ultrathin single-crystalline IrO2(110) films with the gas phase proceeds via the coordinatively unsaturated sites (cus), in particular Ircus, the undercoordinated oxygen species on-top O (Oot) that are coordinated to Ircus, and bridging O (Obr). With the combination of different experimental techniques, such as thermal desorption spectroscopy, scanning tunneling microscopy (STM), high-resolution core-level spectroscopy (HRCLS), infrared spectroscopy, and first-principles studies employing density functional theory calculations, we are able to elucidate surface properties of single-crystalline IrO2(110). We provide spectroscopic fingerprints of the active surface sites of IrO2(110). The freshly prepared IrO2(110) surface is virtually inactive toward gas-phase molecules. The IrO2(110) surface needs to be activated by annealing to 500-600 K under ultrahigh vacuum (UHV) conditions. In the activation step, Ircus sites are liberated from on-top oxygen (Oot) and monoatomic Ir metal islands are formed on the surface, leading to the formation of a bifunctional model catalyst. Vacant Ircus sites of IrO2(110) allow for strong interaction and accommodation of molecules from the gas phase. For instance, CO can adsorb atop on Ircus and water forms a strongly bound water layer on the activated IrO2(110) surface. Single-crystalline IrO2(110) is thermally not very stable although chemically stable. Chemical reduction of IrO2(110) by extensive CO exposure at 473 K is not observed, which is in contrast to the prototypical RuO2(110) system.
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39. |
- Abdelhak, Ahmed, et al.
(author)
-
Prognostic performance of blood neurofilament light chain protein in hospitalized COVID-19 patients without major central nervous system manifestations: an individual participant data meta-analysis.
- 2023
-
In: Journal of neurology. - : Springer. - 1432-1459 .- 0340-5354. ; 270:7, s. 3315-3328
-
Journal article (peer-reviewed)abstract
- To investigate the prognostic value of blood neurofilament light chain protein (NfL) levels in the acute phase of coronavirus disease 2019 (COVID-19).We conducted an individual participant data (IPD) meta-analysis after screening on MEDLINE and Scopus to May 23rd2022. We included studies with hospitalized adult COVID-19 patients without major COVID-19-associated central nervous system (CNS) manifestations and with a measurement of blood NfL in the acute phase as well as data regarding at least one clinical outcome including intensive care unit (ICU)admission, need of mechanical ventilation (MV) and death. We derived the age-adjusted measures NfL Z scores and conducted mixed-effects modelling to test associations between NfL Z scores and other variables, encompassing clinical outcomes. Summary receiver operating characteristic curves (SROCs) were used to calculate the area under the curve (AUC) for blood NfL.We identified 382 records, of which 7 studies were included with a total of 669 hospitalized COVID-19 cases (mean age 66.2±15.0years, 68.1% males). Median NfL Z score at admission was elevated compared to the age-corrected reference population (2.37, IQR: 1.13-3.06, referring to 99th percentile in healthy controls). NfL Z scores were significantly associated with disease duration and severity. Higher NfL Z scores were associated with ahigher likelihood of ICU admission, need ofMV, and death. SROCs revealed AUCs of 0.74, 0.80 and 0.71 for mortality, need ofMV and ICU admission, respectively.Blood NfL levels were elevated in the acute phase of COVID-19 patients without major CNS manifestations and associated with clinical severity and poor outcome. The marker might ameliorate the performance of prognostic multivariable algorithms in COVID-19.
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40. |
- Akel, Sarah, et al.
(author)
-
Neurofilament light, glial fibrillary acidic protein, and tau in a regional epilepsy cohort: High plasma levels are rare but related to seizures
- 2023
-
In: Epilepsia. - 0013-9580. ; 64:10, s. 2690-2700
-
Journal article (peer-reviewed)abstract
- Objective: Higher levels of biochemical blood markers of brain injury have been described immediately after tonic-clonic seizures and in drug-resistant epilepsy, but the levels of such markers in epilepsy in general have not been well characterized. We analyzed neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and tau in a regional hospital-based epilepsy cohort and investigated what proportion of patients have levels suggesting brain injury, and whether certain epilepsy features are associated with high levels.Methods: Biomarker levels were measured in 204 patients with an epilepsy diagnosis participating in a prospective regional biobank study, with age and sex distribution correlating closely to that of all patients seen for epilepsy in the health care region. Absolute biomarker levels were assessed between two patient groups: patients reporting seizures within the 2 months preceding inclusion and patients who did not have seizures for more than 1 year. We also assessed the proportion of patients with above-normal levels of NfL.Results: NfL and GFAP, but not tau, increased with age. Twenty-seven patients had abnormally high levels of NfL. Factors associated with such levels were recent seizures (p = .010) and epileptogenic lesion on radiology (p = .001). Levels of NfL (p = .006) and GFAP (p = .032) were significantly higher in young patients (<65 years) with seizures & LE;2 months before inclusion compared to those who reported no seizures for >1 year. NfL and GFAP correlated weakly with the number of days since last seizure (NfL: r(s) = -.228, p = .007; GFAP: r(s) = -.167, p = .048) in young patients. NfL also correlated weakly with seizure frequency in the last 2 months (r(s) = .162, p = .047).Significance: Most patients with epilepsy do not have biochemical evidence of brain injury. The association with seizures merits further study; future studies should aim for longitudinal sampling and examine whether individual variations in NfL or GFAP levels could reflect seizure activity.
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41. |
- Alawode, Deborah O T, et al.
(author)
-
Transitioning from cerebrospinal fluid to blood tests to facilitate diagnosis and disease monitoring in Alzheimer's disease.
- 2021
-
In: Journal of internal medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 290:3, s. 583-601
-
Journal article (peer-reviewed)abstract
- Alzheimer's disease (AD) is increasingly prevalent worldwide, and disease-modifying treatments may soon be at hand; hence now, more than ever, there is a need to develop techniques that allow earlier and more secure diagnosis. Current biomarker-based guidelines for AD diagnosis, which have replaced the historical symptom-based guidelines, rely heavily on neuroimaging and cerebrospinal fluid (CSF) sampling. Whilst these have greatly improved the diagnostic accuracy of AD pathophysiology, they are less practical for application in primary care, population-based and epidemiological settings, or where resources are limited. In contrast, blood is a more accessible and cost-effective source of biomarkers in AD. In this review paper, using the recently proposed amyloid, tau and neurodegeneration [AT(N)] criteria as a framework towards a biological definition of AD, we discuss recent advances in biofluid-based biomarkers, with a particular emphasis on those with potential to be translated into blood-based biomarkers. We provide an overview of the research conducted both in CSF and in blood to draw conclusions on biomarkers that show promise. Given the evidence collated in this review, plasma neurofilament light chain (N), and phosphorylated tau (p-tau; T) show particular potential for translation into clinical practice. However, p-tau requires more comparisons to be conducted between its various epitopes before conclusions can be made as to which one most robustly differentiates AD from non-AD dementias. Plasma amyloid beta (A) would prove invaluable as an early screening modality, but it requires very precise tests and robust pre-analytical protocols.
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42. |
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43. |
- Ali, Muhammad, et al.
(author)
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Leveraging large multi-center cohorts of Alzheimer disease endophenotypes to understand the role of Klotho heterozygosity on disease risk.
- 2022
-
In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:5
-
Journal article (peer-reviewed)abstract
- Two genetic variants in strong linkage disequilibrium (rs9536314 and rs9527025) in the Klotho (KL) gene, encoding a transmembrane protein, implicated in longevity and associated with brain resilience during normal aging, were recently shown to be associated with Alzheimer disease (AD) risk in cognitively normal participants who are APOE ε4 carriers. Specifically, the participants heterozygous for this variant (KL-SVHET+) showed lower risk of developing AD. Furthermore, a neuroprotective effect of KL-VSHET+ has been suggested against amyloid burden for cognitively normal participants, potentially mediated via the regulation of redox pathways. However, inconsistent associations and a smaller sample size of existing studies pose significant hurdles in drawing definitive conclusions. Here, we performed a well-powered association analysis between KL-VSHET+ and five different AD endophenotypes; brain amyloidosis measured by positron emission tomography (PET) scans (n = 5,541) or cerebrospinal fluid Aβ42 levels (CSF; n = 5,093), as well as biomarkers associated with tau pathology: the CSF Tau (n = 5,127), phosphorylated Tau (pTau181; n = 4,778) and inflammation: CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2; n = 2,123) levels. Our results found nominally significant associations of KL-VSHET+ status with biomarkers for brain amyloidosis (e.g., CSF Aβ positivity; odds ratio [OR] = 0.67 [95% CI, 0.55-0.78], β = 0.72, p = 0.007) and tau pathology (e.g., biomarker positivity for CSF Tau; OR = 0.39 [95% CI, 0.19-0.77], β = -0.94, p = 0.007, and pTau; OR = 0.50 [95% CI, 0.27-0.96], β = -0.68, p = 0.04) in cognitively normal participants, 60-80 years old, who are APOE e4-carriers. Our work supports previous findings, suggesting that the KL-VSHET+ on an APOE ε4 genotype background may modulate Aβ and tau pathology, thereby lowering the intensity of neurodegeneration and incidence of cognitive decline in older controls susceptible to AD.
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44. |
- Alwahabi, ZT, et al.
(author)
-
Infrared polarization spectroscopy of CO2 at atmospheric pressure
- 2004
-
In: Optics Communications. - : Elsevier BV. - 0030-4018. ; 233:4-6, s. 373-381
-
Journal article (peer-reviewed)abstract
- Polarisation spectroscopy (PS) was used to probe CO2 gas concentration in a CO2/N-2 binary mixture at atmospheric pressure and ambient temperature. The CO2 molecules were probed by a direct laser excitation to an overtone and combination vibrational state. The tuneable narrow linewidth infrared laser radiation at 2 mum was obtained by Raman shifting of the output from a single-longitudinal-mode pulsed alexandrite laser-system to the second Stokes component in a H, gas cell. Infrared polarisation spectroscopy (IRPS) and time-resolved infrared laser-induced fluorescence (IRLIF) spectra were collected. A linear dependence of the IRPS signal on the CO2 mole fraction has been found. This indicates that the IRPS signal is only weakly affected by the molecular collisions and that the inter- and intra- molecular energy transfer processes do not strongly influence the molecular alignment at the time scale of the measurements. Thus IRPS holds great potential for quantitative instantaneous gas concentration diagnostics in general. This is especially important for molecules which do not posses an accessible optical transition such as CO, CO2 and N2O. In addition, an accurate experimental method to measure the extinction ratio of the IR polarisers employed in this study has been developed and applied. With its obvious merits as simplicity, easy alignment and high accuracy, the method can be generalized to all spectral regions, different polarisers and high extinction ratios.
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45. |
- Alwahabi, Z. T., et al.
(author)
-
High resolution polarization spectroscopy and laser induced fluorescence of CO2 around 2 mu m
- 2007
-
In: European Physical Journal D. Atomic, Molecular, Optical and Plasma Physics. - : Springer Science and Business Media LLC. - 1434-6060. ; 42:1, s. 41-47
-
Journal article (peer-reviewed)abstract
- High resolution Infrared Polarisation Spectroscopy (IRPS) and Infrared Laser Induced Fluorescence (IRLIF) techniques were used to probe CO2/N-2 binary gas mixture at atmospheric pressure and ambient temperature. The probed CO2 molecules were prepared by laser excitation to an overtone and combination ro-vibrational state (12(0)1, J = 15) of CO2, centred at 4988.6612 cm(-1). IRPS and IRLIF line profiles were recorded for several CO2/N-2 binary mixtures. The observed IRLIF line shapes have the expected Lorentzian form while the observed IRPS line shapes are narrower by a factor of two than those recorded with the IRLIF and appear to have a Lorentzian-cubed profile. The recorded line profiles provide measurements of the pressure-broadening coefficient directly at atmospheric pressure. The Full-Width-Half-Maxima (FWHM) pressure broadening coefficients are measured, based on IRLIF, to be 0.2174 0.0092 cm(-1) atm(-1) and 0.1327 +/- 0.0077 cm(-1) atm(-1) for self- and N-2 collision broadening, respectively. The broadening coefficients obtained based on IRPS were measured to be similar to 8% larger than those obtained with IRLIF.
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46. |
- Alwahabi, Z. T., et al.
(author)
-
Measurements of collisional broadening coefficients by infrared polarization spectroscopy
- 2007
-
In: Applied Spectroscopy. - : SAGE Publications. - 1943-3530 .- 0003-7028. ; 61:4, s. 424-427
-
Journal article (peer-reviewed)abstract
- We present measurements of collisional broadening coefficients, obtained at atmospheric pressure, by polarization spectroscopy. Using tunable single mode laser radiation at similar to 2 pro, high-resolution infrared polarization spectra were recorded for CO2-Ar and CO2-He binary mixtures. The recorded polarization spectra were fitted with a Lorentzian cubed function form to obtain the broadening coefficients. The full-width at half-maxima (FWHM) collisional broadening rates of CO2 by Ar and He, for the R14 (12(0)1 <- 00(0)0) line, have been determined to be 0.161 +/- 0.018 cm(-1) atm(-1) and 0.1823 +/- 0.0032 cm(-1) atm(-1), respectively.
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47. |
- Alwahabi, Z. T., et al.
(author)
-
Vibrational relaxation of CO2 (12(0)1) by argon
- 2009
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In: Chemical Physics. - : Elsevier BV. - 0301-0104. ; 359:1-3, s. 71-76
-
Journal article (peer-reviewed)abstract
- We present experimental measurements of the vibrational relaxation of CO2 (12(0)1) by argon, at ambient temperature (295 +/- 2 K). The CO2 molecules were directly excited to the (12(0)1, J = 14) ro-vibrational state by a tunable laser radiation at similar to 2 mu m. Time-resolved infrared fluorescence technique was used to study the collisional relaxation process. The bimolecular deactivation rate constant of CO2 (12(0)1) by argon was found to be (825 +/- 43 Torr(-1) s(-1)) while the self-deactivation by CO2 (00(0)0) was determined to be (3357 +/- 135 Torr(-1) s(-1)). The radiative life-time of the vibrational combination band (12(0)1), tau[CO2 (12(0)1)], was found to be (5.55 +/- 0.27) mu s. Modern angular momentum theory was used to explain values of the deactivation rate measured. It is concluded that the presence of the (08(0)0) state acts like an angular momentum sink leading to a fast deactivation rate of the CO2 (12(0)1) by argon. (C) 2009 Elsevier B.V. All rights reserved.
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48. |
- Amirijoo, Mehdi, et al.
(author)
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On Self-Optimization of the Random Access Procedure in 3G Long Term Evolution
- 2009
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In: Proceedings of the 11th IFIP/IEEE International Symposium on Integrated Network Management. - : IEEE. - 9781424439232 - 9781424439249
-
Conference paper (peer-reviewed)abstract
- Operationally efficient radio networks typically feature a high degree of self-organization. This means less planning efforts and manual intervention, and a potential for better radio resource utilization when network elements adapts its operation to the observed local conditions. The focus in this paper is selfoptimization of the random access channel (RACH) in the 3G Long Term Evolution (LTE). A comprehensive tutorial about the RACH procedure is provided to span the complexity of the selfoptimization. Moreover, the paper addresses RACH key performance metrics and appropriate modeling of the various steps and components of the procedure. Finally, some coupling between parameters and key performance metrics as well as selfoptimization examples are presented together with a feasibility discussion. The main ambition with this workshop paper is to present and define a relevant set of self-optimization problems, rather than to provide a complete solution.
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49. |
- Amirijoo, Mehdi, et al.
(author)
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Towards Random Access Channel Self-Tuning in LTE
- 2009
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In: Proceedings of the 69th IEEE Vehicular Technology Conference. - 9781424425174 ; , s. 1-5
-
Conference paper (peer-reviewed)abstract
- Future radio access networks are expected to show a high degree of self-organization. This paper addresses self-tuning of the random access channel (RACH) in the 3G Long Term Evolution (LTE). The feasibility of self-tuning is investigated by means of simulation, where the coupling between several parameters and the performance of RACH is provided. The conclusion of the simulations is that RACH self-tuning is indeed possible given that UE assisted measurements are available for the self-tuning mechanism.
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50. |
- Andersson, Peder, et al.
(author)
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Predicting neurological outcome after out-of-hospital cardiac arrest with cumulative information; development and internal validation of an artificial neural network algorithm
- 2021
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In: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 25:1
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Journal article (peer-reviewed)abstract
- BackgroundPrognostication of neurological outcome in patients who remain comatose after cardiac arrest resuscitation is complex. Clinical variables, as well as biomarkers of brain injury, cardiac injury, and systemic inflammation, all yield some prognostic value. We hypothesised that cumulative information obtained during the first three days of intensive care could produce a reliable model for predicting neurological outcome following out-of-hospital cardiac arrest (OHCA) using artificial neural network (ANN) with and without biomarkers.MethodsWe performed a post hoc analysis of 932 patients from the Target Temperature Management trial. We focused on comatose patients at 24, 48, and 72 h post-cardiac arrest and excluded patients who were awake or deceased at these time points. 80% of the patients were allocated for model development (training set) and 20% for internal validation (test set). To investigate the prognostic potential of different levels of biomarkers (clinically available and research-grade), patients' background information, and intensive care observation and treatment, we created three models for each time point: (1) clinical variables, (2) adding clinically accessible biomarkers, e.g., neuron-specific enolase (NSE) and (3) adding research-grade biomarkers, e.g., neurofilament light (NFL). Patient outcome was the dichotomised Cerebral Performance Category (CPC) at six months; a good outcome was defined as CPC 1-2 whilst a poor outcome was defined as CPC 3-5. The area under the receiver operating characteristic curve (AUROC) was calculated for all test sets.ResultsAUROC remained below 90% when using only clinical variables throughout the first three days in the ICU. Adding clinically accessible biomarkers such as NSE, AUROC increased from 82 to 94% (p<0.01). The prognostic accuracy remained excellent from day 1 to day 3 with an AUROC at approximately 95% when adding research-grade biomarkers. The models which included NSE after 72 h and NFL on any of the three days had a low risk of false-positive predictions while retaining a low number of false-negative predictions.ConclusionsIn this exploratory study, ANNs provided good to excellent prognostic accuracy in predicting neurological outcome in comatose patients post OHCA. The models which included NSE after 72 h and NFL on all days showed promising prognostic performance.
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