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| 4. |
- Barausse, Enrico, et al.
(författare)
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Prospects for fundamental physics with LISA
- 2020
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Ingår i: General Relativity and Gravitation. - : SPRINGER/PLENUM PUBLISHERS. - 0001-7701 .- 1572-9532. ; 52:8
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this paper, which is of programmatic rather than quantitative nature, we aim to further delineate and sharpen the future potential of the LISA mission in the area of fundamental physics. Given the very broad range of topics that might be relevant to LISA,we present here a sample of what we view as particularly promising fundamental physics directions. We organize these directions through a "science-first" approach that allows us to classify how LISA data can inform theoretical physics in a variety of areas. For each of these theoretical physics classes, we identify the sources that are currently expected to provide the principal contribution to our knowledge, and the areas that need further development. The classification presented here should not be thought of as cast in stone, but rather as a fluid framework that is amenable to change with the flow of new insights in theoretical physics.
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| 7. |
- Aghanim, N., et al.
(författare)
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Planck 2018 results VI. Cosmological parameters
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 641
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Tidskriftsartikel (refereegranskat)abstract
- We present cosmological parameter results from the final full-mission Planck measurements of the cosmic microwave background (CMB) anisotropies, combining information from the temperature and polarization maps and the lensing reconstruction. Compared to the 2015 results, improved measurements of large-scale polarization allow the reionization optical depth to be measured with higher precision, leading to significant gains in the precision of other correlated parameters. Improved modelling of the small-scale polarization leads to more robust constraints on many parameters, with residual modelling uncertainties estimated to affect them only at the 0.5 sigma level. We find good consistency with the standard spatially-flat 6-parameter Lambda CDM cosmology having a power-law spectrum of adiabatic scalar perturbations (denoted base Lambda CDM in this paper), from polarization, temperature, and lensing, separately and in combination. A combined analysis gives dark matter density Omega (c)h(2)=0.120 +/- 0.001, baryon density Omega (b)h(2)=0.0224 +/- 0.0001, scalar spectral index n(s)=0.965 +/- 0.004, and optical depth tau =0.054 +/- 0.007 (in this abstract we quote 68% confidence regions on measured parameters and 95% on upper limits). The angular acoustic scale is measured to 0.03% precision, with 100 theta (*)=1.0411 +/- 0.0003. These results are only weakly dependent on the cosmological model and remain stable, with somewhat increased errors, in many commonly considered extensions. Assuming the base-Lambda CDM cosmology, the inferred (model-dependent) late-Universe parameters are: Hubble constant H-0=(67.4 +/- 0.5) km s(-1) Mpc(-1); matter density parameter Omega (m)=0.315 +/- 0.007; and matter fluctuation amplitude sigma (8)=0.811 +/- 0.006. We find no compelling evidence for extensions to the base-Lambda CDM model. Combining with baryon acoustic oscillation (BAO) measurements (and considering single-parameter extensions) we constrain the effective extra relativistic degrees of freedom to be N-eff=2.99 +/- 0.17, in agreement with the Standard Model prediction N-eff=3.046, and find that the neutrino mass is tightly constrained to Sigma m(nu)< 0.12 eV. The CMB spectra continue to prefer higher lensing amplitudes than predicted in base CDM at over 2 sigma, which pulls some parameters that affect the lensing amplitude away from the Lambda CDM model; however, this is not supported by the lensing reconstruction or (in models that also change the background geometry) BAO data. The joint constraint with BAO measurements on spatial curvature is consistent with a flat universe, Omega (K)=0.001 +/- 0.002. Also combining with Type Ia supernovae (SNe), the dark-energy equation of state parameter is measured to be w(0)=-1.03 +/- 0.03, consistent with a cosmological constant. We find no evidence for deviations from a purely power-law primordial spectrum, and combining with data from BAO, BICEP2, and Keck Array data, we place a limit on the tensor-to-scalar ratio r(0.002)< 0.06. Standard big-bang nucleosynthesis predictions for the helium and deuterium abundances for the base-CDM cosmology are in excellent agreement with observations. The Planck base-Lambda CDM results are in good agreement with BAO, SNe, and some galaxy lensing observations, but in slight tension with the Dark Energy Survey's combined-probe results including galaxy clustering (which prefers lower fluctuation amplitudes or matter density parameters), and in significant, 3.6 sigma, tension with local measurements of the Hubble constant (which prefer a higher value). Simple model extensions that can partially resolve these tensions are not favoured by the Planck data.
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| 8. |
- Hussein, A. E., et al.
(författare)
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Laser-wakefield accelerators for high-resolution X-ray imaging of complex microstructures
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Laser-wakefield accelerators (LWFAs) are high acceleration-gradient plasma-based particle accelerators capable of producing ultra-relativistic electron beams. Within the strong focusing fields of the wakefield, accelerated electrons undergo betatron oscillations, emitting a bright pulse of X-rays with a micrometer-scale source size that may be used for imaging applications. Non-destructive X-ray phase contrast imaging and tomography of heterogeneous materials can provide insight into their processing, structure, and performance. To demonstrate the imaging capability of X-rays from an LWFA we have examined an irregular eutectic in the aluminum-silicon (Al-Si) system. The lamellar spacing of the Al-Si eutectic microstructure is on the order of a few micrometers, thus requiring high spatial resolution. We present comparisons between the sharpness and spatial resolution in phase contrast images of this eutectic alloy obtained via X-ray phase contrast imaging at the Swiss Light Source (SLS) synchrotron and X-ray projection microscopy via an LWFA source. An upper bound on the resolving power of 2.7 ± 0.3 μm of the LWFA source in this experiment was measured. These results indicate that betatron X-rays from laser wakefield acceleration can provide an alternative to conventional synchrotron sources for high resolution imaging of eutectics and, more broadly, complex microstructures.
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| 9. |
- Kettle, B., et al.
(författare)
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Single-Shot Multi-keV X-Ray Absorption Spectroscopy Using an Ultrashort Laser-Wakefield Accelerator Source
- 2019
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Ingår i: Physical Review Letters. - 0031-9007. ; 123:25
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Tidskriftsartikel (refereegranskat)abstract
- Single-shot absorption measurements have been performed using the multi-keV x rays generated by a laser-wakefield accelerator. A 200 TW laser was used to drive a laser-wakefield accelerator in a mode which produced broadband electron beams with a maximum energy above 1 GeV and a broad divergence of ≈15 mrad FWHM. Betatron oscillations of these electrons generated 1.2±0.2×106 photons/eV in the 5 keV region, with a signal-to-noise ratio of approximately 300 1. This was sufficient to allow high-resolution x-ray absorption near-edge structure measurements at the K edge of a titanium sample in a single shot. We demonstrate that this source is capable of single-shot, simultaneous measurements of both the electron and ion distributions in matter heated to eV temperatures by comparison with density functional theory simulations. The unique combination of a high-flux, large bandwidth, few femtosecond duration x-ray pulse synchronized to a high-power laser will enable key advances in the study of ultrafast energetic processes such as electron-ion equilibration.
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| 10. |
- Maitrallain, A., et al.
(författare)
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Parametric study of high-energy ring-shaped electron beams from a laser wakefield accelerator
- 2022
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Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Laser wakefield accelerators commonly produce on-axis, low-divergence, high-energy electron beams. However, a high charge, annular shaped beam can be trapped outside the bubble and accelerated to high energies. Here we present a parametric study on the production of low-energy-spread, ultra-relativistic electron ring beams in a two-stage gas cell. Ring-shaped beams with energies higher than 750 MeV are observed simultaneously with on axis, continuously injected electrons. Often multiple ring shaped beams with different energies are produced and parametric studies to control the generation and properties of these structures were conducted. Particle tracking and particle-in-cell simulations are used to determine properties of these beams and investigate how they are formed and trapped outside the bubble by the wake produced by on-axis injected electrons. These unusual femtosecond duration, high-charge, high-energy, ring electron beams may find use in beam driven plasma wakefield accelerators and radiation sources.
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| 11. |
- Spesyvtsev, R., et al.
(författare)
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Generation of electron high energy beams with a ring-like structure by a dual stage laser wakefield accelerator
- 2019
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Ingår i: Relativistic Plasma Waves and Particle Beams as Coherent and Incoherent Radiation Sources III. - : SPIE. - 9781510627383 ; 11036
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Konferensbidrag (refereegranskat)abstract
- The laser wake-field accelerator (LWFA) traditionally produces high brightness, quasi-monoenergetic electron beams with Gaussian-like spatial and angular distributions. In the present work we investigate the generation of ultra-relativistic beams with ring-like structures in the blowout regime of the LWFA using a dual stage accelerator. A density down-ramp triggers injection after the first stage and is used to produce ring-like electron spectra in the 300 - 600 MeV energy range. These well defined, annular beams are observed simultaneously with the on-axis, high energy electron beams, with a divergence of a few milliradians. The rings have quasi-monoenergetic energy spectra with an RMS spread estimated to be less than 5%. Particle-in-cell simulations confirm that off-axis injection provides the electrons with the initial transverse momentum necessary to undertake distinct betatron oscillations within the plasma bubble during their acceleration process.
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| 12. |
- Streeter, M. J.V., et al.
(författare)
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Characterization of laser wakefield acceleration efficiency with octave spanning near-IR spectrum measurements
- 2022
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Ingår i: Physical Review Accelerators and Beams. - 2469-9888. ; 25:10
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Tidskriftsartikel (refereegranskat)abstract
- We report on experimental measurements of energy transfer efficiencies in a GeV-class laser wakefield accelerator. Both the transfer of energy from the laser to the plasma wakefield and from the plasma to the accelerated electron beam was diagnosed by simultaneous measurement of the deceleration of laser photons and the acceleration of electrons as a function of plasma length. The extraction efficiency, which we define as the ratio of the energy gained by the electron beam to the energy lost by the self-guided laser mode, was maximized at 19±3% by tuning the plasma density and length. The additional information provided by the octave-spanning laser spectrum measurement allows for independent optimization of the plasma efficiency terms, which is required for the key goal of improving the overall efficiency of laser wakefield accelerators.
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| 14. |
- Akiba, K., et al.
(författare)
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The LHCb VELO Upgrade module construction
- 2024
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Ingår i: Journal of Instrumentation. - : Institute of Physics Publishing (IOPP). - 1748-0221. ; 19:6
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Tidskriftsartikel (refereegranskat)abstract
- The LHCb detector has undergone a major upgrade for LHC Run 3. This Upgrade I detector facilitates operation at higher luminosity and utilises full-detector information at the LHC collision rate, critically including the use of vertex information. A new vertex locator system, the VELO Upgrade, has been constructed. The core element of the new VELO are the double-sided pixelated hybrid silicon detector modules which operate in vacuum close to the LHC beam in a high radiation environment. The construction and quality assurance tests of these modules are described in this paper. The modules incorporate 200 mu m thick, n -on -p silicon sensors bump-bonded to 130 nm technology ASICs. These are attached with high precision to a silicon microchannel substrate that uses evaporative CO 2 cooling. The ASICs are controlled and read out with flexible printed circuits that are glued to the substrate and wire -bonded to the chips. The mechanical support of the module is given by a carbon fibre plate, two carbon fibre rods and an aluminium plate. The sensor attachment was achieved with an average precision of 21 mu m, more than 99.5% of all pixels are fully functional, and a thermal figure of merit of 3 Kcm 2 W - 1 was achieved. The production of the modules was successfully completed in 2021, with the final assembly and installation completed in time for data taking in 2022.
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| 15. |
- Brunner, Fabian J., et al.
(författare)
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Application of non-HDL cholesterol for population-based cardiovascular risk stratification : results from the Multinational Cardiovascular Risk Consortium
- 2019
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 394:10215, s. 2173-2183
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Tidskriftsartikel (refereegranskat)abstract
- Background: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment.Methods: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol.Findings: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7–59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0–20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0–1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6–2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0–1·3 to 2·3, 2·0–2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced.Interpretation: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician–patient communication about primary prevention strategies.
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| 19. |
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| 20. |
- Albert, F., et al.
(författare)
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Betatron x-ray radiation from laser-plasma accelerators driven by femtosecond and picosecond laser systems
- 2018
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Ingår i: Physics of Plasmas. - : AIP Publishing. - 1089-7674 .- 1070-664X. ; 25:5
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Tidskriftsartikel (refereegranskat)abstract
- A comparative experimental study of betatron x-ray radiation from laser wakefield acceleration in the blowout and self-modulated regimes is presented. Our experiments use picosecond duration laser pulses up to 150 J (self-modulated regime) and 60 fs duration laser pulses up to 10 J (blowout regime), for plasmas with electronic densities on the order of 1019cm-3. In the self-modulated regime, where betatron radiation has been very little studied compared to the blowout regime, electrons accelerated in the wake of the laser pulse are subject to both the longitudinal plasma and transverse laser electrical fields. As a result, their motion within the wake is relatively complex; consequently, the experimental and theoretical properties of the x-ray source based on self-modulation differ from the blowout regime of laser wakefield acceleration. In our experimental configuration, electrons accelerated up to about 250 MeV and betatron x-ray spectra with critical energies of about 10-20 keV and photon fluxes between 108and 1010photons/eV Sr are reported. Our experiments open the prospect of using betatron x-ray radiation for applications, and the source is competitive with current x-ray backlighting methods on multi-kilojoule laser systems.
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| 25. |
- Neumann, Johannes Tobias, et al.
(författare)
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Prognostic value of cardiovascular biomarkers in the population
- 2024
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 331:22, s. 1898-1909
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies.Objective: To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors.Design, Setting, and Participants: Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age. The median follow-up was 11.8 years.Exposure: Measurement of high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, B-type natriuretic peptide, or high-sensitivity C-reactive protein.Main Outcomes and Measures: The primary outcome was incident atherosclerotic cardiovascular disease, which included all fatal and nonfatal events. The secondary outcomes were all-cause mortality, heart failure, ischemic stroke, and myocardial infarction. Subdistribution hazard ratios (HRs) for the association of biomarkers and outcomes were calculated after adjustment for established risk factors. The additional predictive value of the biomarkers was assessed using the C statistic and reclassification analyses.Results: The analyses included 164054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17211 incident atherosclerotic cardiovascular disease events. All biomarkers were significantly associated with incident atherosclerotic cardiovascular disease (subdistribution HR per 1-SD change, 1.13 [95% CI, 1.11-1.16] for high-sensitivity cardiac troponin I; 1.18 [95% CI, 1.12-1.23] for high-sensitivity cardiac troponin T; 1.21 [95% CI, 1.18-1.24] for N-terminal pro-B-type natriuretic peptide; 1.14 [95% CI, 1.08-1.22] for B-type natriuretic peptide; and 1.14 [95% CI, 1.12-1.16] for high-sensitivity C-reactive protein) and all secondary outcomes. The addition of each single biomarker to a model that included established risk factors improved the C statistic. For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277). The combination of these biomarkers also improved reclassification compared with the conventional model. Improvements in risk prediction were most pronounced for the secondary outcomes of heart failure and all-cause mortality. The incremental value of biomarkers was greater in people aged 65 years or older vs younger people.Conclusions and Relevance: Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality..
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| 26. |
- Pedro, Joana Reis, et al.
(författare)
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Transient gain of function of cannabinoid CB1 receptors in the control of frontocortical glucose consumption in a rat model of Type-1 diabetes
- 2020
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Ingår i: Brain Research Bulletin. - : Elsevier BV. - 0361-9230. ; 161, s. 106-115
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Tidskriftsartikel (refereegranskat)abstract
- Here we aimed to unify some previous controversial reports on changes in both cannabinoid CB1 receptor (CB1R) expression and glucose metabolism in the forebrain of rodent models of diabetes. We determined how glucose metabolism and its modulation by CB1R ligands evolve in the frontal cortex of young adult male Wistar rats, in the first 8 weeks of streptozotocin-induced type-1 diabetes (T1D). We report that frontocortical CB1R protein density was biphasically altered in the first month of T1D, which was accompanied with a reduction of resting glucose uptake ex vivo in acute frontocortical slices that was normalized after eight weeks in T1D. This early reduction of glucose uptake in slices was also restored by ex vivo treatment with both the non-selective CB1R agonists, WIN55212−2 (500 nM) and the CB1R-selective agonist, ACEA (3 μM) while it was exacerbated by the CB1R-selective antagonist, O-2050 (500 nM). These results suggest a gain-of-function for the cerebrocortical CB1Rs in the control of glucose uptake in diabetes. Although insulin and IGF-1 receptor protein densities remained unaffected, phosphorylated GSKα and GSKβ levels showed different profiles 2 and 8 weeks after T1D induction in the frontal cortex. Altogether, the biphasic response in frontocortical CB1R density within a month after T1D induction resolves previous controversial reports on forebrain CB1R levels in T1D rodent models. Furthermore, this study also hints that cannabinoids may be useful to alleviate impaired glucoregulation in the diabetic cortex.
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| 27. |
- Prudencio, Mercedes, et al.
(författare)
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Toward allele-specific targeting therapy and pharmacodynamic marker for spinocerebellar ataxia type 3
- 2020
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 12:566
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Tidskriftsartikel (refereegranskat)abstract
- Spinocerebellar ataxia type 3 (SCA3), caused by a CAG repeat expansion in the ataxin-3 gene (ATXN3), is characterized by neuronal polyglutamine (polyQ) ATXN3 protein aggregates. Although there is no cure for SCA3, gene-silencing approaches to reduce toxic polyQ ATXN3 showed promise in preclinical models. However, a major limitation in translating putative treatments for this rare disease to the clinic is the lack of pharmacodynamic markers for use in clinical trials. Here, we developed an immunoassay that readily detects polyQ ATXN3 proteins in human biological fluids and discriminates patients with SCA3 from healthy controls and individuals with other ataxias. We show that polyQ ATXN3 serves as a marker of target engagement in human fibroblasts, which may bode well for its use in clinical trials. Last, we identified a single-nucleotide polymorphism that strongly associates with the expanded allele, thus providing an exciting drug target to abrogate detrimental events initiated by mutant ATXN3. Gene-silencing strategies for several repeat diseases are well under way, and our results are expected to improve clinical trial preparedness for SCA3 therapies.
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| 28. |
- Ribeiro, Tiago, et al.
(författare)
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Cytotoxicity of portoamides in human cancer cells and analysis of the molecular mechanisms of action
- 2017
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- Portoamides are cyclic peptides produced and released by the cyanobacterial strain Phormidium sp. presumably to interfere with other organisms in their ecosystems (" allelopathy"). Portoamides were previously demonstrated to have an antiproliferative effect on human lung carcinoma cells, but the underlying mechanism of this activity has not been described. In the present work, the effects of portoamides on proliferation were examined in eight human cancer cell lines and two non-carcinogenic cell lines, and major differences in sensitivities were observed. To generate hypotheses with regard to molecular mechanisms of action, quantitative proteomics using 2D gel electrophoresis and MALDI-TOF/ TOF were performed on the colon carcinoma cell line HT-29. The expression of proteins involved in energy metabolism (mitochondrial respiratory chain and pentose phosphate pathway) was found to be affected. The hypothesis of altered energy metabolism was tested in further experiments. Exposure to portoamides resulted in reduced cellular ATP content, likely due to decreased mitochondrial energy production. Mitochondrial hyperpolarization and reduced mitochondrial reductive capacity was observed in treated cells. Furthermore, alterations in the expression of peroxiredoxins (PRDX4, PRDX6) and components of proteasome subunits (PSB4, PSA6) were observed in portoamide-treated cells, but these alterations were not associated with detectable increases in oxidative stress. We conclude that the cytotoxic activity of portoamides is associated with disturbance of energy metabolism, and alterations in mitochondrial structure and function.
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| 29. |
- Vos, Stephanie J. B., et al.
(författare)
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Prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage
- 2015
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Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 138:5, s. 1327-1338
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Tidskriftsartikel (refereegranskat)abstract
- Three sets of research criteria are available for diagnosis of Alzheimer's disease in subjects with mild cognitive impairment: the International Working Group-1, International Working Group-2, and National Institute of Aging-Alzheimer Association criteria. We compared the prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage according to these criteria. Subjects with mild cognitive impairment (n = 1607), 766 of whom had both amyloid and neuronal injury markers, were recruited from 13 cohorts. We used cognitive test performance and available biomarkers to classify subjects as prodromal Alzheimer's disease according to International Working Group-1 and International Working Group-2 criteria and in the high Alzheimer's disease likelihood group, conflicting biomarker groups (isolated amyloid pathology or suspected non-Alzheimer pathophysiology), and low Alzheimer's disease likelihood group according to the National Institute of Ageing-Alzheimer Association criteria. Outcome measures were the proportion of subjects with Alzheimer's disease at the mild cognitive impairment stage and progression to Alzheimer's disease-type dementia. We performed survival analyses using Cox proportional hazards models. According to the International Working Group-1 criteria, 850 (53%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 50% compared to 21% for subjects without prodromal Alzheimer's disease. According to the International Working Group-2 criteria, 308 (40%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 61% compared to 22% for subjects without prodromal Alzheimer's disease. According to the National Institute of Ageing-Alzheimer Association criteria, 353 (46%) subjects were in the high Alzheimer's disease likelihood group, 49 (6%) in the isolated amyloid pathology group, 220 (29%) in the suspected non-Alzheimer pathophysiology group, and 144 (19%) in the low Alzheimer's disease likelihood group. The 3-year progression rate to Alzheimer's disease-type dementia was 59% in the high Alzheimer's disease likelihood group, 22% in the isolated amyloid pathology group, 24% in the suspected non-Alzheimer pathophysiology group, and 5% in the low Alzheimer's disease likelihood group. Our findings support the use of the proposed research criteria to identify Alzheimer's disease at the mild cognitive impairment stage. In clinical settings, the use of both amyloid and neuronal injury markers as proposed by the National Institute of Ageing-Alzheimer Association criteria offers the most accurate prognosis. For clinical trials, selection of subjects in the National Institute of Ageing-Alzheimer Association high Alzheimer's disease likelihood group or the International Working Group-2 prodromal Alzheimer's disease group could be considered.
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| 30. |
- Willeit, Peter, et al.
(författare)
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Natriuretic peptides and integrated risk assessment for cardiovascular disease : an individual-participant-data meta-analysis
- 2016
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Ingår i: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 4:10, s. 840-849
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Tidskriftsartikel (refereegranskat)abstract
- Background: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. Methods: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7.5%, and >= 7.5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure. Findings: We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1.76 (95% CI 1.56-1.98) for the combination of coronary heart disease and stroke and 2.00 (1.77-2.26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0.012 (0.010-0.014) and a net reclassification improvement of 0.027 (0.019-0.036) for the combination of coronary heart disease and stroke and a C-index increase of 0.019 (0.016-0.022) and a net reclassification improvement of 0.028 (0.019-0.038) for the combination of coronary heart disease, stroke, and heart failure. Interpretation: In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention.
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