| 1. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
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| 5. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 6. |
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| 7. |
- Brady, MC, et al.
(författare)
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Precision rehabilitation for aphasia by patient age, sex, aphasia severity, and time since stroke? A prespecified, systematic review-based, individual participant data, network, subgroup meta-analysis
- 2022
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Ingår i: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 17:10, s. 1067-1077
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Tidskriftsartikel (refereegranskat)abstract
- Stroke rehabilitation interventions are routinely personalized to address individuals’ needs, goals, and challenges based on evidence from aggregated randomized controlled trials (RCT) data and meta-syntheses. Individual participant data (IPD) meta-analyses may better inform the development of precision rehabilitation approaches, quantifying treatment responses while adjusting for confounders and reducing ecological bias. Aim: We explored associations between speech and language therapy (SLT) interventions frequency (days/week), intensity (h/week), and dosage (total SLT-hours) and language outcomes for different age, sex, aphasia severity, and chronicity subgroups by undertaking prespecified subgroup network meta-analyses of the RELEASE database. Methods: MEDLINE, EMBASE, and trial registrations were systematically searched (inception-Sept2015) for RCTs, including ⩾ 10 IPD on stroke-related aphasia. We extracted demographic, stroke, aphasia, SLT, and risk of bias data. Overall-language ability, auditory comprehension, and functional communication outcomes were standardized. A one-stage, random effects, network meta-analysis approach filtered IPD into a single optimal model, examining SLT regimen and language recovery from baseline to first post-intervention follow-up, adjusting for covariates identified a-priori. Data were dichotomized by age (⩽/> 65 years), aphasia severity (mild–moderate/ moderate–severe based on language outcomes’ median value), chronicity (⩽/> 3 months), and sex subgroups. We reported estimates of means and 95% confidence intervals. Where relative variance was high (> 50%), results were reported for completeness. Results: 959 IPD (25 RCTs) were analyzed. For working-age participants, greatest language gains from baseline occurred alongside moderate to high-intensity SLT (functional communication 3-to-4 h/week; overall-language and comprehension > 9 h/week); older participants’ greatest gains occurred alongside low-intensity SLT (⩽ 2 h/week) except for auditory comprehension (> 9 h/week). For both age-groups, SLT-frequency and dosage associated with best language gains were similar. Participants ⩽ 3 months post-onset demonstrated greatest overall-language gains for SLT at low intensity/moderate dosage (⩽ 2 SLT-h/week; 20-to-50 h); for those > 3 months, post-stroke greatest gains were associated with moderate-intensity/high-dosage SLT (3–4 SLT-h/week; ⩾ 50 hours). For moderate–severe participants, 4 SLT-days/week conferred the greatest language gains across outcomes, with auditory comprehension gains only observed for ⩾ 4 SLT-days/week; mild–moderate participants’ greatest functional communication gains were associated with similar frequency (⩾ 4 SLT-days/week) and greatest overall-language gains with higher frequency SLT (⩾ 6 days/weekly). Males’ greatest gains were associated with SLT of moderate (functional communication; 3-to-4 h/weekly) or high intensity (overall-language and auditory comprehension; (> 9 h/weekly) compared to females for whom the greatest gains were associated with lower-intensity SLT (< 2 SLT-h/weekly). Consistencies across subgroups were also evident; greatest overall-language gains were associated with 20-to-50 SLT-h in total; auditory comprehension gains were generally observed when SLT > 9 h over ⩾ 4 days/week. Conclusions: We observed a treatment response in most subgroups’ overall-language, auditory comprehension, and functional communication language gains. For some, the maximum treatment response varied in association with different SLT-frequency, intensity, and dosage. Where differences were observed, working-aged, chronic, mild–moderate, and male subgroups experienced their greatest language gains alongside high-frequency/intensity SLT. In contrast, older, moderate–severely impaired, and female subgroups within 3 months of aphasia onset made their greatest gains for lower-intensity SLT. The acceptability, clinical, and cost effectiveness of precision aphasia rehabilitation approaches based on age, sex, aphasia severity, and chronicity should be evaluated in future clinical RCTs.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Tiegs, Scott D., et al.
(författare)
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Global patterns and drivers of ecosystem functioning in rivers and riparian zones
- 2019
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Ingår i: Science Advances. - Washington : American Association of Advancement in Science. - 2375-2548. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth's biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented "next-generation biomonitoring" by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale.
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| 12. |
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| 13. |
- Aidas, Kestutis, et al.
(författare)
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The Dalton quantum chemistry program system
- 2014
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Ingår i: WIREs Computational Molecular Science. - : Wiley. - 1759-0876 .- 1759-0884. ; 4:3, s. 269-284
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Tidskriftsartikel (refereegranskat)abstract
- Dalton is a powerful general-purpose program system for the study of molecular electronic structure at the Hartree-Fock, Kohn-Sham, multiconfigurational self-consistent-field, MOller-Plesset, configuration-interaction, and coupled-cluster levels of theory. Apart from the total energy, a wide variety of molecular properties may be calculated using these electronic-structure models. Molecular gradients and Hessians are available for geometry optimizations, molecular dynamics, and vibrational studies, whereas magnetic resonance and optical activity can be studied in a gauge-origin-invariant manner. Frequency-dependent molecular properties can be calculated using linear, quadratic, and cubic response theory. A large number of singlet and triplet perturbation operators are available for the study of one-, two-, and three-photon processes. Environmental effects may be included using various dielectric-medium and quantum-mechanics/molecular-mechanics models. Large molecules may be studied using linear-scaling and massively parallel algorithms. Dalton is distributed at no cost from for a number of UNIX platforms.
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| 14. |
- de La Vieuville, G., et al.
(författare)
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Faint end of the z similar to 3-7 luminosity function of Lyman-alpha emitters behind lensing clusters observed with MUSE
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 628
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Tidskriftsartikel (refereegranskat)abstract
- Contact. This paper presents the results obtained with the Multi-Unit Spectroscopic Explorer (MUSE) at the ESOVery Large Telescope on the faint end of the Lyman-alpha luminosity function (LF) based on deep observations of four lensing clusters. The goal of our project is to set strong constraints on the relative contribution of the Lyman-alpha emitter (LAE) population to cosmic reionization.Aims. The precise aim of the present study is to further constrain the abundance of LAEs by taking advantage of the magnification provided by lensing clusters to build a blindly selected sample of galaxies which is less biased than current blank field samples in redshift and luminosity. By construction, this sample of LAEs is complementary to those built from deep blank fields, whether observed by MUSE or by other facilities, and makes it possible to determine the shape of the LF at fainter levels, as well as its evolution with redshift.Methods. We selected a sample of 156 LAEs with redshifts between 2.9 <= z <= 6.7 and magnification-corrected luminosities in the range 39 less than or similar to log L-Ly alpha [erg s(-1)] less than or similar to 43. To properly take into account the individual differences in detection conditions between the LAEs when computing the LF, including lensing configurations, and spatial and spectral morphologies, the non-parametric 1/V-max method was adopted. The price to pay to benefit from magnification is a reduction of the effective volume of the survey, together with a more complex analysis procedure to properly determine the effective volume V-max for each galaxy. In this paper we present a complete procedure for the determination of the LF based on IFU detections in lensing clusters. This procedure, including some new methods for masking, effective volume integration and (individual) completeness determinations, has been fully automated when possible, and it can be easily generalized to the analysis of IFU observations in blank fields.Results. As a result of this analysis, the Lyman-alpha LF has been obtained in four different redshift bins: 2.9 < z < 6; 7, 2.9 < z < 4.0, 4 : 0 < z < 5.0; and 5 : 0 < z < 6.7 with constraints down to log L-Ly alpha = 40.5. From our data only, no significant evolution of LF mean slope can be found. When performing a Schechter analysis also including data from the literature to complete the present sample towards the brightest luminosities, a steep faint end slope was measured varying from alpha = -1.69(-0.08)(+0.08) to alpha = -1.87(-0 .12)(+0.12) between the lowest and the highest redshift bins.Conclusions. The contribution of the LAE population to the star formation rate density at z similar to 6 is less than or similar to 50% depending on the luminosity limit considered, which is of the same order as the Lyman-break galaxy (LBG) contribution. The evolution of the LAE contribution with redshift depends on the assumed escape fraction of Lyman-alpha photons, and appears to slightly increase with increasing redshift when this fraction is conservatively set to one. Depending on the intersection between the LAE/LBG populations, the contribution of the observed galaxies to the ionizing flux may suffice to keep the universe ionized at z similar to 6.
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| 15. |
- Verhamme, A., et al.
(författare)
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Recovering the systemic redshift of galaxies from their Lyman alpha line profile
- 2018
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966 .- 1745-3925 .- 1745-3933. ; 478:1, s. L60-L65
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Tidskriftsartikel (refereegranskat)abstract
- The Lyman alpha (Ly alpha) line of Hydrogen is a prominent feature in the spectra of star-forming galaxies, usually redshifted by a few hundreds of km s(-1) compared to the systemic redshift. This large offset hampers follow-up surveys, galaxy pair statistics, and correlations with quasar absorption lines when only Ly alpha is available. We propose diagnostics that can be used to recover the systemic redshift directly from the properties of the Ly alpha line profile. We use spectroscopic observations of Ly alpha emitters for which a precise measurement of the systemic redshift is available. Our sample contains 13 sources detected between z approximate to 3 and z approximate to 6 as part of various multi-unit spectroscopic explorer guaranteed time observations. We also include a compilation of spectroscopic Ly alpha data from the literature spanning a wide redshift range (z approximate to 0-8). First, restricting our analysis to double-peaked Ly alpha spectra, we find a tight correlation between the velocity offset of the red peak with respect to the systemic redshift, V-peak(red), and the separation of the peaks. Secondly, we find a correlation between V-peak(red) and the full width at half-maximum of the Ly alpha line. Fitting formulas to estimate systemic redshifts of galaxies with an accuracy of <= 100 km s(-1), when only the Ly alpha emission line is available, are given for the two methods.
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| 16. |
- Godoy, B. I., et al.
(författare)
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A novel input design approach for systems with quantized output data
- 2014
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Ingår i: 2014 European Control Conference, ECC. - : IEEE. - 9783952426913 ; , s. 1049-1054
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Konferensbidrag (refereegranskat)abstract
- In this paper, we explore the problem of input design for systems with quantized measurements. For the input design problem, we calculate and optimize a function of the Fisher Information Matrix (FIM). The calculation of the FIM is greatly simplified by using known relationships of the derivative of the likelihood function, and the auxiliary function arising from the Expectation Maximization (EM) algorithm. To optimize the FIM, we design an experiment using a recently published method based on graph theory. A numerical example shows that the proposed experiment can be successfully used in quantized systems.
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| 17. |
- Maasri, Alain, et al.
(författare)
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A global agenda for advancing freshwater biodiversity research
- 2022
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 25:2, s. 255-263
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Tidskriftsartikel (refereegranskat)abstract
- Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation.
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| 18. |
- Valenzuela, Patricio Esteban, et al.
(författare)
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Particle-based Gaussian process optimization for input design in nonlinear dynamical models
- 2016
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Ingår i: 2016 IEEE 55th Conference on Decision and Control, CDC 2016. - New York : Institute of Electrical and Electronics Engineers (IEEE). - 9781509018376 ; , s. 2085-2090
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Konferensbidrag (refereegranskat)abstract
- We propose a novel approach to input design for identification of nonlinear state space models. The optimal input sequence is obtained by maximizing a scalar cost function of the Fisher information matrix. Since the Fisher information matrix is unavailable in closed form, it is estimated using particle methods. In addition, we make use of Gaussian process optimization to find the optimal input and to mitigate the problem of a large computational cost incurred by the particle method, as the method reduces the number of functional evaluations. Numerical examples are provided to illustrate the performance of the resulting algorithm.
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| 19. |
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| 20. |
- Ade, Peter, et al.
(författare)
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The Simons Observatory : science goals and forecasts
- 2019
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
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Tidskriftsartikel (refereegranskat)abstract
- The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
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| 21. |
- Akiyama, Kazunori, et al.
(författare)
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First Sagittarius A* Event Horizon Telescope Results. II. EHT and Multiwavelength Observations, Data Processing, and Calibration
- 2022
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
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Tidskriftsartikel (refereegranskat)abstract
- We present Event Horizon Telescope (EHT) 1.3 mm measurements of the radio source located at the position of the supermassive black hole Sagittarius A* (Sgr A*), collected during the 2017 April 5-11 campaign. The observations were carried out with eight facilities at six locations across the globe. Novel calibration methods are employed to account for Sgr A*'s flux variability. The majority of the 1.3 mm emission arises from horizon scales, where intrinsic structural source variability is detected on timescales of minutes to hours. The effects of interstellar scattering on the image and its variability are found to be subdominant to intrinsic source structure. The calibrated visibility amplitudes, particularly the locations of the visibility minima, are broadly consistent with a blurred ring with a diameter of similar to 50 mu as, as determined in later works in this series. Contemporaneous multiwavelength monitoring of Sgr A* was performed at 22, 43, and 86 GHz and at near-infrared and X-ray wavelengths. Several X-ray flares from Sgr A* are detected by Chandra, one at low significance jointly with Swift on 2017 April 7 and the other at higher significance jointly with NuSTAR on 2017 April 11. The brighter April 11 flare is not observed simultaneously by the EHT but is followed by a significant increase in millimeter flux variability immediately after the X-ray outburst, indicating a likely connection in the emission physics near the event horizon. We compare Sgr A*'s broadband flux during the EHT campaign to its historical spectral energy distribution and find that both the quiescent emission and flare emission are consistent with its long-term behavior.
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| 22. |
- Canova, Moara Almeida, et al.
(författare)
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Different ecosystem services, same (dis)satisfaction with compensation : A critical comparison between farmers' perception in Scotland and Brazil
- 2019
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Ingår i: Ecosystem Services. - : Elsevier BV. - 2212-0416 .- 2212-0416. ; 35, s. 164-172
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Tidskriftsartikel (refereegranskat)abstract
- Payments for Ecosystem Services (PES) schemes have increasingly expanded to consider ecosystem services (ESS). In Brazil, the Forest Code permits PES but does not specify the scheme operationalization. The way ESS should be quantified and valued has not yet been implemented country-wide, nor has the funding source for PES. Through interviews with farmers in Rio Claro-SP, Brazil, and in Cairngorms National Park in the highlands and lowlands of Scotland, UK, we compared farmers' perspectives concerning ESS and PES, focusing on the PES implementation in sugarcane landscape in Sao Paulo state. While Scottish farmers perceived more cultural services, Brazilian farmers focused on regulating services, which we attribute to socio-political and landscape differences. Despite these differences, farmers in both areas preferred opportunity cost approach for ESS valuation because this method captures efforts to maintain ESS. Thereby, the opportunity cost should be considered for valuation in PES schemes, but conversely, budgetary constraints make it impossible to satisfy farmers with PES in regions of high productivity in the southeast of Brazil. Lessons learned concerning the PES subsidies in Scotland indicates the importance of co-designing schemes with stakeholders, minimizing trade-offs between the environment. Therefore, the participants as ESS providers, beneficiaries and intermediaries in the public policies arena was recognized for co-optimize the trade-offs between costs and effectiveness in PES.
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| 23. |
- Claeyssens, A., et al.
(författare)
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Spectral variations of Lyman alpha emission within strongly lensed sources observed with MUSE
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 489:4, s. 5022-5029
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Tidskriftsartikel (refereegranskat)abstract
- We present an analysis of HI Lyman alpha emission in deep VLT/MUSE observations of two highly magnified and extended galaxies at z = 3.5 and 4.03, including a newly discovered, almost complete Einstein ring. While these Lyman a haloes are intrinsically similar to the ones typically seen in other MUSE deep fields, the benefits of gravitational lensing allow us to construct exceptionally detailed maps of Lyman alpha line properties at sub-kpc scales. By combining all multiple images, we are able to observe complex structures in the Lyman a emission and uncover small (similar to 120 km s(-1) in Lyman alpha peak shift), but significant at >4 sigma, systematic variations in the shape of the Lyman a line profile within each halo. Indeed, we observe a global trend for the line peak shift to become redder at large radii, together with a strong correlation between the peak wavelength and line width. This systematic intrahalo variation is markedly similar to the object-to-object variations obtained from the integrated properties of recent large samples. Regions of high surface brightness correspond to relatively small line shifts, which could indicate that Lyman alpha emission escapes preferentially from regions where the line profile has been less severely affected by scattering of Lyman alpha photons.
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| 24. |
- Coscieme, Luca, et al.
(författare)
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Multiple conceptualizations of nature are key to inclusivity and legitimacy in global environmental governance
- 2020
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Ingår i: Environmental Science and Policy. - : Elsevier BV. - 1462-9011 .- 1873-6416. ; 104, s. 36-42
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Tidskriftsartikel (refereegranskat)abstract
- Despite increasing scientific understanding of the global environmental crisis, we struggle to adopt the policies science suggests would be effective. One of the reasons for that is the lack of inclusive engagement and dialogue among a wide range of different actors. Furthermore, there is a lack of consideration of differences between languages, worldviews and cultures. In this paper, we propose that engagement across the science-policy interface can be strengthened by being mindful of the breadth and depth of the diverse human-nature relations found around the globe. By examining diverse conceptualizations of nature in more than 60 languages, we identify three clusters: inclusive conceptualizations where humans are viewed as an integral component of nature; non-inclusive conceptualizations where humans are separate from nature; and deifying conceptualizations where nature is understood and experienced within a spiritual dimension. Considering and respecting this rich repertoire of ways of describing, thinking about and relating to nature can help us communicate in ways that resonate across cultures and worldviews. This repertoire also provides a resource we can draw on when defining policies and sustainability scenarios for the future, offering opportunities for finding solutions to global environmental challenges.
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| 25. |
- Dagenais, Gilles R, et al.
(författare)
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Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): a prospective cohort study.
- 2020
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Ingår i: Lancet (London, England). - 1474-547X. ; 395:10226, s. 785-794
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Tidskriftsartikel (refereegranskat)abstract
- To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches.The PURE study is a prospective, population-based cohort study of individuals aged 35-70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years.This analysis assesses the incidence of events in 162534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years (IQR 8·5-10·9). During follow-up, 11307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs (vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs.Among adults aged 35-70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care.Full funding sources are listed at the end of the paper (see Acknowledgments).
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| 26. |
- Godoy, Patricio, et al.
(författare)
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Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME
- 2013
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 87:8, s. 1315-1530
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Forskningsöversikt (refereegranskat)abstract
- This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4 alpha, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4 alpha), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell-derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun.
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| 27. |
- Hernandez, Marcela, et al.
(författare)
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Isolation and characterization of a novel simazine-degrading bacterium from agricultural soil of central Chile, Pseudomonas sp MHP41
- 2008
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Ingår i: Fems Microbiology Letters. - : Oxford University Press (OUP). - 0378-1097 .- 1574-6968. ; 286:2, s. 184-190
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Tidskriftsartikel (refereegranskat)abstract
- s-Triazine herbicides are used extensively in South America in agriculture and forestry. In this study, a bacterium designated as strain MHP41, capable of degrading simazine and atrazine, was isolated from agricultural soil in the Quillota valley, central Chile. Strain MHP41 is able to grow in minimal medium, using simazine as the sole nitrogen source. In this medium, the bacterium exhibited a growth rate of μ=0.10 h−1, yielding a high biomass of 4.2 × 108 CFU mL−1. Resting cells of strain MHP41 degrade more than 80% of simazine within 60 min. The atzA, atzB, atzC, atzD, atzE and atzF genes encoding the enzymes of the simazine upper and lower pathways were detected in strain MHP41. The motile Gram-negative bacterium was identified as a Pseudomonas sp., based on the Biolog microplate system and comparative sequence analyses of the 16S rRNA gene. Amplified ribosomal DNA restriction analysis allowed the differentiation of strain MHP41 from Pseudomonas sp. ADP. The comparative 16S rRNA gene sequence analyses suggested that strain MHP41 is closely related to Pseudomonas nitroreducens and Pseudomonas multiresinovorans. This is the first s-triazine-degrading bacterium isolated in South America. Strain MHP41 is a potential biocatalyst for the remediation of s-triazine-contaminated environments.
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| 28. |
- Levin, Johannes, et al.
(författare)
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α-Synuclein seed amplification assay detects Lewy body co-pathology in autosomal dominant Alzheimer's disease late in the disease course and dependent on Lewy pathology burden
- 2024
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Ingår i: Alzheimer's and Dementia. - 1552-5260. ; 20:6, s. 4351-4365
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Amyloid beta and tau pathology are the hallmarks of sporadic Alzheimer's disease (AD) and autosomal dominant AD (ADAD). However, Lewy body pathology (LBP) is found in ≈ 50% of AD and ADAD brains. METHODS: Using an α-synuclein seed amplification assay (SAA) in cerebrospinal fluid (CSF) from asymptomatic (n = 26) and symptomatic (n = 27) ADAD mutation carriers, including 12 with known neuropathology, we investigated the timing of occurrence and prevalence of SAA positive reactivity in ADAD in vivo. RESULTS: No asymptomatic participant and only 11% (3/27) of the symptomatic patients tested SAA positive. Neuropathology revealed LBP in 10/12 cases, primarily affecting the amygdala or the olfactory areas. In the latter group, only the individual with diffuse LBP reaching the neocortex showed α-synuclein seeding activity in CSF in vivo. DISCUSSION: Results suggest that in ADAD LBP occurs later than AD pathology and often as amygdala- or olfactory-predominant LBP, for which CSF α-synuclein SAA has low sensitivity. Highlights: Cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC) detects misfolded α-synuclein in ≈ 10% of symptomatic autosomal dominant Alzheimer's disease (ADAD) patients. CSF RT-QuIC does not detect α-synuclein seeding activity in asymptomatic mutation carriers. Lewy body pathology (LBP) in ADAD mainly occurs as olfactory only or amygdala-predominant variants. LBP develops late in the disease course in ADAD. CSF α-synuclein RT-QuIC has low sensitivity for focal, low-burden LBP.
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| 29. |
- Lim, Michelle, et al.
(författare)
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Early-career experts essential for planetary sustainability
- 2017
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Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 29, s. 151-157
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Forskningsöversikt (refereegranskat)abstract
- Early-career experts can play a fundamental role in achieving planetary sustainability by bridging generational divides and developing novel solutions to complex problems. We argue that intergenerational partnerships and interdisciplinary collaboration among early-career experts will enable emerging sustainability leaders to contribute fully to a sustainable future. We review 16 international, interdisciplinary, and sustainability-focused early-career capacity building programs. We conclude that such programs are vital to developing sustainability leaders of the future and that decision-making for sustainability is likely to be best served by strong institutional cultures that promote intergenerational learning and involvement.
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| 30. |
- Lin, Amy Erica, et al.
(författare)
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Clonal Hematopoiesis of Indeterminate Potential With Loss of Tet2 Enhances Risk for Atrial Fibrillation Through Nlrp3 Inflammasome Activation
- 2024
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Ingår i: Circulation. - 0009-7322. ; 149:18, s. 1419-1434
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP), a common age-associated phenomenon, associates with increased risk of both hematological malignancy and cardiovascular disease. Although CHIP is known to increase the risk of myocardial infarction and heart failure, the influence of CHIP in cardiac arrhythmias, such as atrial fibrillation (AF), is less explored. METHODS: CHIP prevalence was determined in the UK Biobank, and incident AF analysis was stratified by CHIP status and clone size using Cox proportional hazard models. Lethally irradiated mice were transplanted with hematopoietic-specific loss of Tet2, hematopoietic-specific loss of Tet2 and Nlrp3, or wild-type control and fed a Western diet, compounded with or without NLRP3 (NLR [NACHT, LRR {leucine rich repeat}] family pyrin domain containing protein 3) inhibitor, NP3-361, for 6 to 9 weeks. Mice underwent in vivo invasive electrophysiology studies and ex vivo optical mapping. Cardiomyocytes from Ldlr−/− mice with hematopoietic-specific loss of Tet2 or wild-type control and fed a Western diet were isolated to evaluate calcium signaling dynamics and analysis. Cocultures of pluripotent stem cell-derived atrial cardiomyocytes were incubated with Tet2deficient bone marrow-derived macrophages, wild-type control, or cytokines IL-1β (interleukin 1β) or IL-6 (interleukin 6). RESULTS: Analysis of the UK Biobank showed individuals with CHIP, in particular TET2 CHIP, have increased incident AF. Hematopoietic-specific inactivation of Tet2 increases AF propensity in atherogenic and nonatherogenic mouse models and is associated with increased Nlrp3 expression and CaMKII (Ca2+/calmodulin-dependent protein kinase II) activation, with AF susceptibility prevented by inactivation of Nlrp3. Cardiomyocytes isolated from Ldlr−/− mice with hematopoietic inactivation of Tet2 and fed a Western diet have impaired calcium release from the sarcoplasmic reticulum into the cytosol, contributing to atrial arrhythmogenesis. Abnormal sarcoplasmic reticulum calcium release was recapitulated in cocultures of cardiomyocytes with the addition of Tet2-deficient macrophages or cytokines IL-1β or IL-6. CONCLUSIONS: We identified a modest association between CHIP, particularly TET2 CHIP, and incident AF in the UK Biobank population. In a mouse model of AF resulting from hematopoietic-specific inactivation of Tet2, we propose altered calcium handling as an arrhythmogenic mechanism, dependent on Nlrp3 inflammasome activation. Our data are in keeping with previous studies of CHIP in cardiovascular disease, and further studies into the therapeutic potential of NLRP3 inhibition for individuals with TET2 CHIP may be warranted.
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| 31. |
- Metra, Marco, et al.
(författare)
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y Effects of Serelaxin in Patients with Acute Heart Failure
- 2019
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 381:8, s. 716-726
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSerelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. MethodsIn this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 mu g per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days.ResultsA total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups.ConclusionsIn this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.) In a randomized trial, 6545 patients with acute heart failure were assigned to either serelaxin or placebo in addition to standard care. There were no significant differences between the two groups in the incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days.
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| 32. |
- Migueles, Jairo H., et al.
(författare)
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Step-Based Metrics and Overall Physical Activity in Children With Overweight or Obesity: Cross-Sectional Study
- 2020
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Ingår i: JMIR mhealth and uhealth. - : JMIR PUBLICATIONS, INC. - 2291-5222. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Best-practice early interventions to increase physical activity (PA) in children with overweight and obesity should be both feasible and evidence based. Walking is a basic human movement pattern that is practical, cost-effective, and does not require complex movement skills. However, there is still a need to investigate how much walking-as a proportion of total PA level-is performed by children who are overweight and obese in order to determine its utility as a public health strategy. Objective: This study aimed to (1) investigate the proportion of overall PA indicators that are explained by step-based metrics and (2) study step accumulation patterns relative to achievement of public health recommendations in children who are overweight and obese. Methods: A total of 105 overweight and obese children (mean 10.1 years of age [SD 1.1]; 43 girls) wore hip-worn accelerometers for 7 days. PA volumes were derived using the daily average of counts per 15 seconds, categorized using standard cut points for light-moderate-vigorous PA (LMVPA) and moderate-to-vigorous PA (MVPA). Derived step-based metrics included volume (steps/day), time in cadence bands, and peak 1-minute, 30-minute, and 60-minute cadences. Results: Steps per day explained 66%, 40%, and 74% of variance for counts per 15 seconds, LMVPA, and MVPA, respectively. The variance explained was increased up to 80%, 92%, and 77% by including specific cadence bands and peak cadences. Children meeting the World Health Organization recommendation of 60 minutes per day of MVPA spent less time at zero cadence and more time in cadence bands representing sporadic movement to brisk walking (ie, 20-119 steps/min) than their less-active peers. Conclusions: Step-based metrics, including steps per day and various cadence-based metrics, seem to capture a large proportion of PA for children who are overweight and obese. Given the availability of pedometers, step-based metrics could be useful in discriminating between those children who do or do not achieve MVPA recommendations.
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| 33. |
- Mintzer, Scott, et al.
(författare)
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Effects of adjunctive eslicarbazepine acetate on serum lipids in patients with partial-onset seizures: Impact of concomitant statins and enzyme-inducing antiepileptic drugs.
- 2018
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Ingår i: Epilepsy research. - : Elsevier BV. - 1872-6844 .- 0920-1211. ; 141, s. 83-89
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the effects of eslicarbazepine acetate (ESL) on lipid metabolism and to determine whether reduced statin exposure during ESL therapy has clinical consequences.We conducted a post-hoc analysis of pooled data for serum lipids (laboratory values) from three phase III, multicenter, randomized, double-blind, placebo-controlled trials of adjunctive ESL therapy (400, 800, or 1200mg once daily) in patients with treatment-refractory partial-onset seizures. Changes from baseline in serum lipid levels were analyzed according to use of statins and/or enzyme-inducing antiepileptic drugs (EIAEDs) during the baseline period.In total, 426 and 1021 placebo- and ESL-treated patients, respectively, were included in the analysis. With regard to the changes from baseline in serum concentrations, there were statistically significant differences between the placebo and ESL 1200mg QD groups, for both total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), but the effect sizes were small (+4.1mg/dL and +1.8mg/dL, respectively). A small but significant difference in low-density lipoprotein cholesterol (LDL-C; -5.0mg/dL) was observed between the ESL 400mg QD group and the placebo group. In patients not taking a concomitant EIAED, there were no changes with ESL 400mg QD, but modest and statistically significant increases in cholesterol fractions (TC, LDL-C and HDL-C) with ESL 800mg QD (<6mg/dL) and ESL 1200mg QD (<10mg/dL). ESL had no consistent effect on lipids in patients taking a concomitant EIAED. In patients taking statins during baseline, there were no clinically relevant changes in serum lipids during use of ESL, although the subgroups were small.These results suggest that ESL does not appear to have clinically significant effects on serum lipids, nor does the pharmacokinetic interaction between ESL and statins have an impact on serum lipid concentrations.
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| 34. |
- Ortega, Francisco B., et al.
(författare)
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Effects of an Exercise Program on Brain Health Outcomes for Children With Overweight or Obesity The ActiveBrains Randomized Clinical Trial
- 2022
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Ingår i: JAMA Network Open. - : American Medical Association. - 2574-3805. ; 5:8
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Pediatric overweight and obesity are highly prevalent across the world, with implications for poorer cognitive and brain health. Exercise might potentially attenuate these adverse consequences. OBJECTIVES To investigate the effects of an exercise program on brain health indicators, including intelligence, executive function, academic performance, and brain outcomes, among children with overweight or obesity and to explore potential mediators and moderators of the main effects of exercise. DESIGN, SETTING, AND PARTICIPANTS All preexercise and postexercise data for this 20-week randomized clinical trial of 109 children aged 8 to 11 years with overweight or obesity were collected from November 21, 2014, to June 30, 2016, with neuroimaging data processing and analyses conducted between June 1, 2017, and December 20, 2021. All 109 children were included in the intention-to-treat analyses; 90 children (82.6%) completed the postexercise evaluation and attended 70% or more of the recommended exercise sessions and were included in per-protocol analyses. INTERVENTIONS All participants received lifestyle recommendations. The control group continued their usual routines, whereas the exercise group attended a minimum of 3 supervised 90-minute sessions per week in an out-of-school setting. MAIN OUTCOMES AND MEASURES Intelligence, executive function (cognitive flexibility, inhibition, and working memory), and academic performance were assessed with standardized tests, and hippocampal volume was measured with magnetic resonance imaging. RESULTS The 109 participants included 45 girls (41.3%); participants had a mean (SD) body mass index of 26.8 (3.6) and a mean (SD) age of 10.0 (1.1) years at baseline. In per-protocol analyses, the exercise intervention improved crystallized intelligence, with the exercise group improving from before exercise to after exercise (mean z score, 0.62 [95% CI, 0.44-0.80]) compared with the control group (mean z score, -0.10 [95% CI, -0.28 to 0.09]; difference between groups, 0.72 SDs [95% CI, 0.46-0.97]; P < .001). Total intelligence also improved significantly more in the exercise group (mean z score, 0.69 [95% CI, 0.48-0.89]) than in the control group (mean z score, 0.07 [95% CI, -0.14 to 0.28]; difference between groups, 0.62 SDs [95% CI, 0.31-0.91]; P < .001). Exercise also positively affected a composite score of cognitive flexibility (mean z score: exercise group, 0.25 [95% CI, 0.05-0.44]; control group, -0.17 [95% CI, -0.39 to 0.04]; difference between groups, 0.42 SDs [95% CI, 0.13-0.71]; P = .005). These main effects were consistent in intention-to-treat analyses and after multiple-testing correction. There was a positive, small-magnitude effect of exercise on total academic performance (mean z score: exercise group, 0.31 [95% CI, 0.18-0.44]; control group, 0.10 [95% CI, -0.04 to 0.24]; difference between groups, 0.21 SDs [95% CI, 0.01-0.40]; P = .03), which was partially mediated by cognitive flexibility. Inhibition, working memory, hippocampal volume, and other brain magnetic resonance imaging outcomes studied were not affected by the exercise program. The intervention increased cardiorespiratory fitness performance as indicated by longer treadmill time to exhaustion (mean z score: exercise group, 0.54 [95% CI, 0.27-0.82]; control group, 0.13 [95% CI, -0.16 to 0.41]; difference between groups, 0.42 SDs [95% CI, 0.01-0.82]; P = .04), and these changes in fitness mediated some of the effects (small percentage of mediation [approximately 10%-20%]). The effects of exercise were overall consistent across the moderators tested, except for larger improvements in intelligence among boys compared with girls. CONCLUSIONS AND RELEVANCE In this randomized clinical trial, exercise positively affected intelligence and cognitive flexibility during development among children with overweight or obesity. However, the structural and functional brain changes responsible for these improvements were not identified.
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| 35. |
- Valenzuela, Patricio E., et al.
(författare)
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A graph/particle-based method for experiment design in nonlinear systems
- 2014
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Ingår i: IFAC Proceedings Volumes. - : Elsevier BV. - 1474-6670.
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Konferensbidrag (refereegranskat)abstract
- We present an extended method for experiment design in nonlinear state space models. The proposed input design method optimizes a scalar cost function of the information matrix, by computing the optimal stationary probability mass function (pmf) from which an input sequence is sampled. The feasible set of the stationary pmf is a polytope, allowing it to be expressed as a convex combination of its extreme points. The extreme points in the feasible set of pmf's can be computed using graph theory. Therefore, the final information matrix can be approximated as a convex combination of the information matrices associated with each extreme point. For nonlinear systems, the information matrices for each extreme point can be computed by using particle methods. Numerical examples show that the proposed technique can be successfully employed for experiment design in nonlinear systems.
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| 36. |
- Valenzuela, Patricio E., et al.
(författare)
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On model order priors for Bayesian identification of SISO linear systems
- 2019
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Ingår i: International Journal of Control. - : Taylor & Francis. - 0020-7179 .- 1366-5820. ; 92:7, s. 1645-1661
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Tidskriftsartikel (refereegranskat)abstract
- A method for the identification of single input single output linear systems is presented. The method employs a Bayesian approach to compute the posterior distribution of the model parameters given the data-set. Since this distribution is often unavailable in closed form, a Metropolis Hastings algorithm is implemented to draw samples from it. To implement the sampler, the inclusion of prior information regarding the model order of the identified system is discussed. As one of the main contributions of this work, a prior over the Hankel singular values of the model is imposed. Numerical examples illustrate the method.
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| 37. |
- Valenzuela, Patricio E., et al.
(författare)
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On robust input design for nonlinear dynamical models
- 2017
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Ingår i: Automatica. - : Elsevier. - 0005-1098 .- 1873-2836. ; 77, s. 268-278
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Tidskriftsartikel (refereegranskat)abstract
- We present a method for robust input design for nonlinear state-space models. The method optimizes a scalar cost function of the Fisher information matrix over a set of marginal distributions of stationary processes. By using elements from graph theory we characterize such a set. Since the true system is unknown, the resulting optimization problem takes the uncertainty on the true value of the parameters into account. In addition, the required estimates of the information matrix are computed using particle methods, and the resulting problem is convex in the decision variables. Numerical examples illustrate the proposed technique by identifying models using the expectation–maximization algorithm.
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