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1.
  • Barragan, O., et al. (författare)
  • The young HD 73583 (TOI-560) planetary system: two 10-M-circle plus mini-Neptunes transiting a 500-Myr-old, bright, and active K dwarf
  • 2022
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 514:2, s. 1606-1627
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the discovery and characterization of two transiting planets observed by TESS in the light curves of the young and bright (V = 9.67) star HD73583 (TOI-560). We perform an intensive spectroscopic and photometric space- and ground-based follow-up in order to confirm and characterize the system. We found that HD73583 is a young (similar to 500 Myr) active star with a rotational period of 12.08 +/- 0.11 d, and a mass and radius of 0.73 +/- 0.02 M-circle dot and 0.65 +/- 0.02 R-circle dot, respectively. HD 73583 b (P-b = 6.3980420(-0.0000062)(+0.0000067 )d) has a mass and radius of 10.2(-3.1)(+3.4) M-circle plus and 2.79 +/- 0.10 R-circle plus, respectively, which gives a density of 2.58(-0.81)(+0.95) g cm(-3). HD 73583 c (P-c = 18.87974(-0.00074)(+0.00086) d) has a mass and radius of 9.7(-1.7)(+1.8) M-circle plus and 2.39(-0.09)(+0.10) R-circle plus, respectively, which translates to a density of 3.88(-0.80)(+0.91) g cm(-3). Both planets are consistent with worlds made of a solid core surrounded by a volatile envelope. Because of their youth and host star brightness, they both are excellent candidates to perform transmission spectroscopy studies. We expect ongoing atmospheric mass-loss for both planets caused by stellar irradiation. We estimate that the detection of evaporating signatures on H and He would be challenging, but doable with present and future instruments.
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2.
  • Kuhle, J., et al. (författare)
  • Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study
  • 2015
  • Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 21:8, s. 1013-1024
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and objective: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. Methods: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. Results: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. Conclusions: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.
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  • Allaria, E., et al. (författare)
  • Highly coherent and stable pulses from the FERMI seeded free-electron laser in the extreme ultraviolet
  • 2012
  • Ingår i: Nature Photonics. - 1749-4885. ; 6:10, s. 699-704
  • Tidskriftsartikel (refereegranskat)abstract
    • Free-electron lasers (FELs) are promising devices for generating light with laser-like properties in the extreme ultraviolet and X-ray spectral regions. Recently, FELs based on the self-amplified spontaneous emission (SASE) mechanism have allowed major breakthroughs in diffraction and spectroscopy applications, despite the relatively large shot-to-shot intensity and photon-energy fluctuations and the limited longitudinal coherence inherent in the SASE mechanism. Here, we report results on the initial performance of the FERMI seeded FEL, based on the high-gain harmonic generation configuration, in which an external laser is used to initiate the emission process. Emission from the FERMI FEL-1 source occurs in the form of pulses carrying energy of several tens of microjoules per pulse and tunable throughout the 65 to 20 nm wavelength range, with unprecedented shot-to-shot wavelength stability, low-intensity fluctuations, close to transform-limited bandwidth, transverse and longitudinal coherence and full control of polarization.
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6.
  • Georgieva, Iskra, 1987, et al. (författare)
  • Hot planets around cool stars - two short-period mini-Neptunes transiting the late K-dwarf TOI-1260
  • 2021
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 505:4, s. 4684-4701
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the discovery and characterization of two sub-Neptunes in close orbits, as well as a tentative outer planet of a similar size, orbiting TOI-1260 - a low metallicity K6V dwarf star. Photometry from Transiting Exoplanet Survey Satellite(TESS) yields radii of R-b = 2.33 +/- 0.10 and R-c = 2.82 +/- 0.15 R-circle plus, and periods of 3.13 and 7.49 d for TOI-1260b and TOI-1260c, respectively. We combined the TESS data with a series of ground-based follow-up observations to characterize the planetary system. From HARPS-N high-precision radial velocities we obtain M-b = and M-c = M-circle plus. The star is moderately active with a complex activity pattern, which necessitated the use of Gaussian process regression for both the light-curve detrending and the radial velocity modelling, in the latter case guided by suitable activity indicators. We successfully disentangle the stellar-induced signal from the planetary signals, underlining the importance and usefulness of the Gaussian process approach. We test the system's stability against atmospheric photoevaporation and find that the TOI-1260 planets are classic examples of the structure and composition ambiguity typical for the 2-3 R-circle plus range.
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7.
  • Hoyer, S., et al. (författare)
  • TOI-220b: a warm sub-Neptune discovered by TESS
  • 2021
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 505:3, s. 3361-3379
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper, we report the discovery of TOI-220b, a new sub-Neptune detected by the Transiting Exoplanet Survey Satellite (TESS) and confirmed by radial velocity follow-up observations with the HARPS spectrograph. Based on the combined analysis of TESS transit photometry and high precision radial velocity measurements, we estimate a planetary mass of 13.8 +/- 1.0M(circle plus) and radius of 3.03 +/- 0.15R(circle plus), implying a bulk density of 2.73 +/- 0.47. TOI-220b orbits a relative bright (V=10.4) and old (10.1 +/- 1.4Gyr) K dwarf star with a period of similar to 10.69d. Thus, TOI-220b is a new warm sub-Neptune with very precise mass and radius determinations. A Bayesian analysis of the TOI-220b internal structure indicates that due to the strong irradiation it receives, the low density of this planet could be explained with a steam atmosphere in radiative-convective equilibrium and a supercritical water layer on top of a differentiated interior made of a silicate mantle and a small iron core.
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8.
  • Mallorquin, M., et al. (författare)
  • TOI-1801 b: A temperate mini-Neptune around a young M0.5 dwarf
  • 2023
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 680
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the discovery, mass, and radius determination of TOI-1801 b, a temperate mini-Neptune around a young M dwarf. TOI-1801 b was observed in TESS sectors 22 and 49, and the alert that this was a TESS planet candidate with a period of 21.3 days went out in April 2020. However, ground-based follow-up observations, including seeing-limited photometry in and outside transit together with precise radial velocity (RV) measurements with CARMENES and HIRES revealed that the true period of the planet is 10.6 days. These observations also allowed us to retrieve a mass of 5.74 +/- 1.46 M-circle plus, which together with a radius of 2.08 +/- 0.12 R-circle plus, means that TOI-1801 b is most probably composed of water and rock, with an upper limit of 2% by mass of H-2 in its atmosphere. The stellar rotation period of 16 days is readily detectable in our RV time series and in the ground-based photometry. We derived a likely age of 600-800 Myr for the parent star TOI-1801, which means that TOI-1801 b is the least massive young mini-Neptune with precise mass and radius determinations. Our results suggest that if TOI-1801 b had a larger atmosphere in the past, it must have been removed by some evolutionary mechanism on timescales shorter than 1 Gyr.
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  • Turtelboom,, et al. (författare)
  • The TESS-Keck Survey. XI. Mass Measurements for Four Transiting Sub-Neptunes Orbiting K Dwarf TOI-1246
  • 2022
  • Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 163:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Multiplanet systems are valuable arenas for investigating exoplanet architectures and comparing planetary siblings. TOI-1246 is one such system, with a moderately bright K dwarf (V = 11.6, K = 9.9) and four transiting sub-Neptunes identified by TESS with orbital periods of 4.31, 5.90, 18.66, and 37.92 days. We collected 130 radial velocity observations with Keck/HIRES and TNG/HARPS-N to measure planet masses. We refit the 14 sectors of TESS photometry to refine planet radii (2.97 +/- 0.06 R (circle plus), 2.47 +/- 0.08 R (circle plus), 3.46 +/- 0.09 R (circle plus), and 3.72 +/- 0.16 R (circle plus)) and confirm the four planets. We find that TOI-1246 e is substantially more massive than the three inner planets (8.1 +/- 1.1 M (circle plus), 8.8 +/- 1.2 M (circle plus), 5.3 +/- 1.7 M (circle plus), and 14.8 +/- 2.3 M (circle plus)). The two outer planets, TOI-1246 d and TOI-1246 e, lie near to the 2:1 resonance (P (e)/P ( d ) = 2.03) and exhibit transit-timing variations. TOI-1246 is one of the brightest four-planet systems, making it amenable for continued observations. It is one of only five systems with measured masses and radii for all four transiting planets. The planet densities range from 0.70 +/- 0.24 to 3.21 +/- 0.44 g cm(-3), implying a range of bulk and atmospheric compositions. We also report a fifth planet candidate found in the RV data with a minimum mass of 25.6 +/- 3.6 M (circle plus). This planet candidate is exterior to TOI-1246 e, with a candidate period of 93.8 days, and we discuss the implications if it is confirmed to be planetary in nature.
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10.
  • Tuson, A., et al. (författare)
  • TESS and CHEOPS discover two warm sub-Neptunes transiting the bright K-dwarf HD 15906
  • 2023
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 523:2, s. 3090-3118
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the discovery of two warm sub-Neptunes transiting the bright (G = 9.5 mag) K-dwarf HD 15906 (TOI 461, TIC 4646810). This star was observed by the Transiting Exoplanet Survey Satellite (TESS) in sectors 4 and 31, revealing two small transiting planets. The inner planet, HD 15906 b, was detected with an unambiguous period but the outer planet, HD 15906 c, showed only two transits separated by ∼ 734 d, leading to 36 possible values of its period. We performed follow-up observations with the CHaracterising ExOPlanet Satellite (CHEOPS) to confirm the true period of HD 15906 c and improve the radius precision of the two planets. From TESS, CHEOPS, and additional ground-based photometry, we find that HD 15906 b has a radius of 2.24 ± 0.08 R and a period of 10.924709 ± 0.000032 d, whilst HD 15906 c has a radius of 2.93+−000607 R and a period of 21.583298+−00000055000052 d. Assuming zero bond albedo and full day-night heat redistribution, the inner and outer planet have equilibrium temperatures of 668 ± 13 K and 532 ± 10 K, respectively. The HD 15906 system has become one of only six multiplanet systems with two warm (700 K) sub-Neptune sized planets transiting a bright star (G ≤ 10 mag). It is an excellent target for detailed characterization studies to constrain the composition of sub-Neptune planets and test theories of planet formation and evolution.
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11.
  • Chaturvedi, P., et al. (författare)
  • TOI-1468: A system of two transiting planets, a super-Earth and a mini-Neptune, on opposite sides of the radius valley
  • 2022
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 666
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the discovery and characterization of two small transiting planets orbiting the bright M3.0V star TOI-1468 (LSPM J0106+1913), whose transit signals were detected in the photometric time series in three sectors of the TESS mission. We confirm the planetary nature of both of them using precise radial velocity measurements from the CARMENES and MAROON-X spectrographs, and supplement them with ground-based transit photometry. A joint analysis of all these data reveals that the shorter-period planet, TOI-1468 b (P-b = 1.88 d), has a planetary mass of M-b = 3.21 +/- 0.24M(circle plus) and a radius of R-b = 1.280(-0.039)(+0.038) R-circle plus, resulting in a density of rho(b) = 8.39(-0.92)(+1.05) g cm(-3), which is consistent with a mostly rocky composition. For the outer planet, TOI-1468 c (P-c = 15.53 d), we derive a mass of M-c = 6.64(-0.68)(+0.67) M-circle plus,aradius of R-c = 2.06 +/- 0.04 R-circle plus, and a bulk density of rho(c) = 2.00(-0.19)(+0.21) g cm(-3), which corresponds to a rocky core composition with a H/He gas envelope. These planets are located on opposite sides of the radius valley, making our system an interesting discovery as there are only a handful of other systems with the same properties. This discovery can further help determine a more precise location of the radius valley for small planets around M dwarfs and, therefore, shed more light on planet formation and evolution scenarios.
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12.
  • Hori, Yasunori, et al. (författare)
  • The Discovery and Follow-up of Four Transiting Short-period Sub-Neptunes Orbiting M Dwarfs
  • 2024
  • Ingår i: Astronomical Journal. - 1538-3881 .- 0004-6256. ; 167:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Sub-Neptunes with radii of 2-3 R ⊕ are intermediate in size between rocky planets and Neptune-sized planets. The orbital properties and bulk compositions of transiting sub-Neptunes provide clues to the formation and evolution of close-in small planets. In this paper, we present the discovery and follow-up of four sub-Neptunes orbiting M dwarfs (TOI-782, TOI-1448, TOI-2120, and TOI-2406), three of which were newly validated by ground-based follow-up observations and statistical analyses. TOI-782 b, TOI-1448 b, TOI-2120 b, and TOI-2406 b have radii of R p = 2.740 − 0.079 + 0.082 R ⊕ , 2.769 − 0.068 + 0.073 R ⊕ , 2.120 ± 0.067 R ⊕, and 2.830 − 0.066 + 0.068 R ⊕ and orbital periods of P = 8.02, 8.11, 5.80, and 3.08 days, respectively. Doppler monitoring with the Subaru/InfraRed Doppler instrument led to 2σ upper limits on the masses of <19.1 M ⊕, <19.5 M ⊕, <6.8 M ⊕, and <15.6 M ⊕ for TOI-782 b, TOI-1448 b, TOI-2120 b, and TOI-2406 b, respectively. The mass-radius relationship of these four sub-Neptunes testifies to the existence of volatile material in their interiors. These four sub-Neptunes, which are located above the so-called “radius valley,” are likely to retain a significant atmosphere and/or an icy mantle on the core, such as a water world. We find that at least three of the four sub-Neptunes (TOI-782 b, TOI-2120 b, and TOI-2406 b), orbiting M dwarfs older than 1 Gyr, are likely to have eccentricities of e ∼ 0.2-0.3. The fact that tidal circularization of their orbits is not achieved over 1 Gyr suggests inefficient tidal dissipation in their interiors.
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13.
  • Knudstrup, E., et al. (författare)
  • Radial velocity confirmation of a hot super-Neptune discovered by TESS with a warm Saturn-mass companion
  • 2023
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 519:4, s. 5637-5655
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the discovery and confirmation of the planetary system TOI-1288. This late G dwarf harbours two planets: TOI-1288 b and TOI-1288 c. We combine TESS space-borne and ground-based transit photometry with HARPS-N and HIRES high-precision Doppler measurements, which we use to constrain the masses of both planets in the system and the radius of planet b. TOI-1288 b has a period of 2.699835(-0.000003)(+0.000004) d, a radius of 5.24 +/- 0.09 R-circle plus, and a mass of 42 +/- 3 M-circle plus, making this planet a hot transiting super-Neptune situated right in the Neptunian desert. This desert refers to a paucity of Neptune-sized planets on short period orbits. Our 2.4-yr-long Doppler monitoring of TOI-1288 revealed the presence of a Saturn-mass planet on a moderately eccentric orbit (0.13(-0.09)(+0.07)) with a minimum mass of 84 +/- 7 M-circle plus and a period of 443(-13)(+11) d. The five sectors worth of TESS data do not cover our expected mid-transit time for TOI-1288 c, and we do not detect a transit for this planet in these sectors.
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  • Wilson, D., et al. (författare)
  • Development and multi-center validation of a fully automated digital immunoassay for neurofilament light chain: toward a clinical blood test for neuronal injury
  • 2024
  • Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 62:2, s. 322-331
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Neurofilament light chain (NfL) has emerged as a promising biomarker for detecting and monitoring axonal injury. Until recently, NfL could only be reliably measured in cerebrospinal fluid, but digital single molecule array (Simoa) technology has enabled its precise measurement in blood samples where it is typically 50-100 times less abundant. We report development and multi-center validation of a novel fully automated digital immunoassay for NfL in serum for informing axonal injury status.Methods A 45-min immunoassay for serum NfL was developed for use on an automated digital analyzer based on Simoa technology. The analytical performance (sensitivity, precision, reproducibility, linearity, sample type) was characterized and then cross validated across 17 laboratories in 10 countries. Analytical performance for clinical NfL measurement was examined in individual patients with relapsing remitting multiple sclerosis (RRMS) after 3 months of disease modifying treatment (DMT) with fingolimod.Results The assay exhibited a lower limit of detection (LLoD) of 0.05 ng/L, a lower limit of quantification (LLoQ) of 0.8 ng/L, and between-laboratory imprecision <10 % across 17 validation sites. All tested samples had measurable NfL concentrations well above the LLoQ. In matched pre-post treatment samples, decreases in NfL were observed in 26/29 RRMS patients three months after DMT start, with significant decreases detected in a majority of patients.Conclusions The sensitivity characteristics and reproducible performance across laboratories combined with full automation make this assay suitable for clinical use for NfL assessment, monitoring in individual patients, and cross-comparisons of results across multiple sites.
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16.
  • Fissolo, N., et al. (författare)
  • Serum biomarker levels predict disability progression in patients with primary progressive multiple sclerosis
  • 2024
  • Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - 0022-3050. ; 95:5, s. 410-418
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundWe aimed to investigate the potential of serum biomarker levels to predict disability progression in a multicentric real-world cohort of patients with primary progressive multiple sclerosis (PPMS).MethodsA total of 141 patients with PPMS from 18 European MS centres were included. Disability progression was investigated using change in Expanded Disability Status Scale (EDSS) score over three time intervals: baseline to 2 years, 6 years and to the last follow-up. Serum levels of neurofilament light chain (sNfL), glial fibrillar acidic protein (sGFAP) and chitinase 3-like 1 (sCHI3L1) were measured using single-molecule array assays at baseline. Correlations between biomarker levels, and between biomarkers and age were quantified using Spearman's r. Univariable and multivariable linear models were performed to assess associations between biomarker levels and EDSS change over the different time periods.ResultsMedian (IQR) age of patients was 52.9 (46.4-58.5) years, and 58 (41.1%) were men. Median follow-up time was 9.1 (7.0-12.6) years. Only 8 (5.7%) patients received treatment during follow-up. sNfL and sGFAP levels were moderately correlated (r=0.43) and both weakly correlated with sCHI3L1 levels (r=0.19 and r=0.17, respectively). In multivariable analyses, levels of the three biomarkers were associated with EDSS changes across all time periods. However, when analysis was restricted to non-inflammatory patients according to clinical and radiological parameters (n=64), only sCHI3L1 levels remained associated with future EDSS change.ConclusionsLevels of sNfL, sGFAP and sCHI3L1 are prognostic biomarkers associated with disability progression in patients with PPMS, being CHI3L1 findings less dependent on the inflammatory component associated with disease progression.
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18.
  • La Manno, G, et al. (författare)
  • RNA velocity of single cells
  • 2018
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 560:7719, s. 494-
  • Tidskriftsartikel (refereegranskat)
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  • Sangeorzan, Irina, et al. (författare)
  • Toward Shared Decision-Making in Degenerative Cervical Myelopathy : Protocol for a Mixed Methods Study
  • 2023
  • Ingår i: JMIR Research Protocols. - : JMIR Publications. - 1929-0748. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Health care decisions are a critical determinant in the evolution of chronic illness. In shared decision-making (SDM), patients and clinicians work collaboratively to reach evidence-based health decisions that align with individual circumstances, values, and preferences. This personalized approach to clinical care likely has substantial benefits in the oversight of degenerative cervical myelopathy (DCM), a type of nontraumatic spinal cord injury. Its chronicity, heterogeneous clinical presentation, complex management, and variable disease course engenders an imperative for a patient-centric approach that accounts for each patient's unique needs and priorities. Inadequate patient knowledge about the condition and an incomplete understanding of the critical decision points that arise during the course of care currently hinder the fruitful participation of health care providers and patients in SDM. This study protocol presents the rationale for deploying SDM for DCM and delineates the groundwork required to achieve this.Objective: The study's primary outcome is the development of a comprehensive checklist to be implemented upon diagnosis that provides patients with essential information necessary to support their informed decision-making. This is known as a core information set (CIS). The secondary outcome is the creation of a detailed process map that provides a diagrammatic representation of the global care workflows and cognitive processes involved in DCM care. Characterizing the critical decision points along a patient's journey will allow for an effective exploration of SDM tools for routine clinical practice to enhance patient-centered care and improve clinical outcomes.Methods: Both CISs and process maps are coproduced iteratively through a collaborative process involving the input and consensus of key stakeholders. This will be facilitated by Myelopathy.org, a global DCM charity, through its Research Objectives and Common Data Elements for Degenerative Cervical Myelopathy community. To develop the CIS, a 3-round, web-based Delphi process will be used, starting with a baseline list of information items derived from a recent scoping review of educational materials in DCM, patient interviews, and a qualitative survey of professionals. A priori criteria for achieving consensus are specified. The process map will be developed iteratively using semistructured interviews with patients and professionals and validated by key stakeholders.Results: Recruitment for the Delphi consensus study began in April 2023. The pilot-testing of process map interview participants started simultaneously, with the formulation of an initial baseline map underway.Conclusions: This protocol marks the first attempt to provide a starting point for investigating SDM in DCM. The primary work centers on developing an educational tool for use in diagnosis to enable enhanced onward decision-making. The wider objective is to aid stakeholders in developing SDM tools by identifying critical decision junctures in DCM care. Through these approaches, we aim to provide an exhaustive launchpad for formulating SDM tools in the wider DCM community.
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22.
  • Abdelhak, Ahmed, et al. (författare)
  • Prognostic performance of blood neurofilament light chain protein in hospitalized COVID-19 patients without major central nervous system manifestations: an individual participant data meta-analysis.
  • 2023
  • Ingår i: Journal of neurology. - : Springer. - 1432-1459 .- 0340-5354. ; 270:7, s. 3315-3328
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate the prognostic value of blood neurofilament light chain protein (NfL) levels in the acute phase of coronavirus disease 2019 (COVID-19).We conducted an individual participant data (IPD) meta-analysis after screening on MEDLINE and Scopus to May 23rd2022. We included studies with hospitalized adult COVID-19 patients without major COVID-19-associated central nervous system (CNS) manifestations and with a measurement of blood NfL in the acute phase as well as data regarding at least one clinical outcome including intensive care unit (ICU)admission, need of mechanical ventilation (MV) and death. We derived the age-adjusted measures NfL Z scores and conducted mixed-effects modelling to test associations between NfL Z scores and other variables, encompassing clinical outcomes. Summary receiver operating characteristic curves (SROCs) were used to calculate the area under the curve (AUC) for blood NfL.We identified 382 records, of which 7 studies were included with a total of 669 hospitalized COVID-19 cases (mean age 66.2±15.0years, 68.1% males). Median NfL Z score at admission was elevated compared to the age-corrected reference population (2.37, IQR: 1.13-3.06, referring to 99th percentile in healthy controls). NfL Z scores were significantly associated with disease duration and severity. Higher NfL Z scores were associated with ahigher likelihood of ICU admission, need ofMV, and death. SROCs revealed AUCs of 0.74, 0.80 and 0.71 for mortality, need ofMV and ICU admission, respectively.Blood NfL levels were elevated in the acute phase of COVID-19 patients without major CNS manifestations and associated with clinical severity and poor outcome. The marker might ameliorate the performance of prognostic multivariable algorithms in COVID-19.
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  • Adameyko, I, et al. (författare)
  • Sox2 and Mitf cross-regulatory interactions consolidate progenitor and melanocyte lineages in the cranial neural crest
  • 2012
  • Ingår i: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 139:2, s. 397-410
  • Tidskriftsartikel (refereegranskat)abstract
    • The cellular origin and molecular mechanisms regulating pigmentation of head and neck are largely unknown. Melanocyte specification is controlled by the transcriptional activity of Mitf, but no general logic has emerged to explain how Mitf and progenitor transcriptional activities consolidate melanocyte and progenitor cell fates. We show that cranial melanocytes arise from at least two different cellular sources: initially from nerve-associated Schwann cell precursors (SCPs) and later from a cellular source that is independent of nerves. Unlike the midbrain-hindbrain cluster from which melanoblasts arise independently of nerves, a large center of melanocytes in and around cranial nerves IX-X is derived from SCPs, as shown by genetic cell-lineage tracing and analysis of ErbB3-null mutant mice. Conditional gain- and loss-of-function experiments show genetically that cell fates in the neural crest involve both the SRY transcription factor Sox2 and Mitf, which consolidate an SCP progenitor or melanocyte fate by cross-regulatory interactions. A gradual downregulation of Sox2 in progenitors during development permits the differentiation of both neural crest- and SCP-derived progenitors into melanocytes, and an initial small pool of nerve-associated melanoblasts expands in number and disperses under the control of endothelin receptor B (Ednrb) and Wnt5a signaling.
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25.
  • Avsic-Zupanc, T, et al. (författare)
  • Hemorrhagic fever with renal syndrome in the Dolenjska region of Slovenia--a 10-year survey.
  • 1999
  • Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 28:4, s. 860-5
  • Tidskriftsartikel (refereegranskat)abstract
    • This report describes the first investigation of clinical findings for a larger series of patients with hemorrhagic fever with renal syndrome (HFRS) who were infected with Dobrava virus. From 1985 to 1995, 38 patients with serologically confirmed HFRS were hospitalized at the regional hospital in Novo mesto in the Dolenjska region of Slovenia. On the basis of results of serological examination, 24 patients had Dobrava virus infection, and 14 patients had Puumala virus infection. Complete clinical data were available for 31 patients. Eleven patients underwent hemodialysis for treatment of acute oliguric or anuric renal failure. Four patients, all infected by Dobrava virus, had signs of shock and severe bleeding. Three severely ill Dobrava virus-infected patients died of hemorrhagic complications. We have demonstrated that Dobrava and Puumala viruses coexist in a single region of endemicity and are capable of causing HFRS with significant differences in severity.
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26.
  • Brignole, Michele, et al. (författare)
  • Low-blood pressure phenotype underpins the tendency to reflex syncope
  • 2021
  • Ingår i: Journal of Hypertension. - 1473-5598. ; 39:7, s. 1319-1325
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: We hypothesized that cardiovascular physiology differs in reflex syncope patients compared with the general population, predisposing such individuals to vasovagal reflex.METHODS: In this multicohort cross-sectional study, we compared aggregate data of resting SBP, DBP, pulse pressure (PP) and heart rate (HR), collected from six community-based cohort studies (64 968 observations) with those from six databases of reflex syncope patients (6516 observations), subdivided by age decades and sex.RESULTS: Overall, in male individuals with reflex syncope, SBP (-3.4 mmHg) and PP (-9.2 mmHg) were lower and DBP (+2.8 mmHg) and HR (+5.1 bpm) were higher than in the general population; the difference in SBP was higher at ages above 60 years. In female individuals, PP (-6.0 mmHg) was lower and DBP (+4.7 mmHg) and HR (+4.5 bpm) were higher than in the general population; differences in SBP were less pronounced, becoming evident only above 60 years. Compared with male individuals, SBP in female individuals exhibited slower increase until age 40 years, and then demonstrated steeper increase that continued throughout remaining life.CONCLUSION: The patients prone to reflex syncope demonstrate a different resting cardiovascular haemodynamic profile as compared with a general population, characterized by lower SBP and PP, reflecting reduced venous return and lower stroke volume, and a higher HR and DBP, suggesting the activation of compensatory mechanisms. Our data contribute to a better understanding why some individuals with similar demographic characteristics develop reflex syncope and others do not.VIDEO ABSTRACT: http://links.lww.com/HJH/B580.
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28.
  • Furlan, J., et al. (författare)
  • Pipe loop testing of a mixture containing fine, dense solids with magnetic properties
  • 2019
  • Ingår i: 19th International Conference on Transport &amp; Sedimentation of Solid Particles. - : Wydawnictwo Uniwersytetu Przyrodniczego we Wrocławiu (Wrocław University of Environmental and Life Sciences). ; , s. 23-29
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Tests were performed in the GIW Hydraulic Laboratory on a milled copper slag tailings slurry in pipe loops with 75 and 100 mm diameter loss sections. Volumetric concentrations of 1 to 14% were tested in the 100 mm loop, and the initial results, derived using magnetic flow meter measurements, showed pressure losses approximately equal to that of water. Chemical Testing of the solid particles was performed, and they were found to be made up of 56% magnetite by weight. Magnetite has been found in the past (Sonar Trac paper) to effect magnetic flow meter measurements, which was the primary method being used in this test program. Secondary measurements using a Sonar Trac instrument indicated, in contrast, the more common and expected equivalent fluid behavior in the 4” loop at the lower concentrations, where the losses, when expressed in height of slurry, now landed on top of the carrier liquid curve, which was found to be equal to that of water. A comparison between the measurements from the magnetic flow meter, and those from the sonar trac, showed a linear dependency between the flow rate ratio (between the magnetic flow meter measurement and the sonar trac measurement) and the solids concentration. These tests illustrate the importance of having knowledge of the makeup of the solid particles in a slurry, and the utility of acoustic based flow rate measurement methods in cases where magnetite (or other solids particles with magnetic properties) particles are present within the slurry.
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31.
  • La Manno, Gioele, et al. (författare)
  • Molecular architecture of the developing mouse brain
  • 2021
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 596:7870, s. 92-96
  • Tidskriftsartikel (refereegranskat)abstract
    • The mammalian brain develops through a complex interplay of spatial cues generated by diffusible morphogens, cell-cell interactions and intrinsic genetic programs that result in probably more than a thousand distinct cell types. A complete understanding of this process requires a systematic characterization of cell states over the entire spatiotemporal range of brain development. The ability of single-cell RNA sequencing and spatial transcriptomics to reveal the molecular heterogeneity of complex tissues has therefore been particularly powerful in the nervous system. Previous studies have explored development in specific brain regions(1-8), the whole adult brain(9) and even entire embryos(10). Here we report a comprehensive single-cell transcriptomic atlas of the embryonic mouse brain between gastrulation and birth. We identified almost eight hundred cellular states that describe a developmental program for the functional elements of the brain and its enclosing membranes, including the early neuroepithelium, region-specific secondary organizers, and both neurogenic and gliogenic progenitors. We also used in situ mRNA sequencing to map the spatial expression patterns of key developmental genes. Integrating the in situ data with our single-cell clusters revealed the precise spatial organization of neural progenitors during the patterning of the nervous system. A comprehensive single-cell transcriptomic atlas of the mouse brain between gastrulation and birth identifies hundreds of cellular states and reveals the spatiotemporal organization of brain development.
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32.
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33.
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34.
  • Oddo, Dominic, et al. (författare)
  • Characterization of a Set of Small Planets with TESS and CHEOPS and an Analysis of Photometric Performance
  • 2023
  • Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 165:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The radius valley carries implications for how the atmospheres of small planets form and evolve, but this feature is visible only with highly precise characterizations of many small planets. We present the characterization of nine planets and one planet candidate with both NASA TESS and ESA CHEOPS observations, which adds to the overall population of planets bordering the radius valley. While five of our planets—TOI 118 b, TOI 262 b, TOI 455 b, TOI 560 b, and TOI 562 b—have already been published, we vet and validate transit signals as planetary using follow-up observations for four new TESS planets, including TOI 198 b, TOI 244 b, TOI 444 b, and TOI 470 b. While a three times increase in primary mirror size should mean that one CHEOPS transit yields an equivalent model uncertainty in transit depth as about nine TESS transits in the case that the star is equally as bright in both bands, we find that our CHEOPS transits typically yield uncertainties equivalent to between two and 12 TESS transits, averaging 5.9 equivalent transits. Therefore, we find that while our fits to CHEOPS transits provide overall lower uncertainties on transit depth and better precision relative to fits to TESS transits, our uncertainties for these fits do not always match expected predictions given photon-limited noise. We find no correlations between number of equivalent transits and any physical parameters, indicating that this behavior is not strictly systematic, but rather might be due to other factors such as in-transit gaps during CHEOPS visits or nonhomogeneous detrending of CHEOPS light curves.
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37.
  • Rodriguez-Furlan, Cecilia, et al. (författare)
  • Interaction between VPS35 and RABG3f is necessary as a checkpoint to control fusion of late compartments with the vacuole
  • 2019
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:42, s. 21291-21301
  • Tidskriftsartikel (refereegranskat)abstract
    • Vacuoles are essential organelles in plants, playing crucial roles, such as cellular material degradation, ion and metabolite storage, and turgor maintenance. Vacuoles receive material via the endocytic, secretory, and autophagic pathways. Membrane fusion is the last step during which prevacuolar compartments (PVCs) and autophagosomes fuse with the vacuole membrane (tonoplast) to deliver cargoes. Protein components of the canonical intracellular fusion machinery that are conserved across organisms, including Arabidopsis thaliana, include complexes, such as soluble N-ethylmaleimidesensitive factor attachment protein receptors (SNAREs), that catalyze membrane fusion, and homotypic fusion and vacuole protein sorting (HOPS), that serve as adaptors which tether cargo vesicles to target membranes for fusion under the regulation of RAB-GTPases. The mechanisms regulating the recruitment and assembly of tethering complexes are not well-understood, especially the role of RABs in this dynamic regulation. Here, we report the identification of the small synthetic molecule Endosidin17 (E517), which interferes with synthetic, endocytic, and autophagic traffic by impairing the fusion of late endosome compartments with the tonoplast. Multiple independent target identification techniques revealed that E517 targets the VPS35 subunit of the retromer tethering complex, preventing its normal interaction with the Arabidopsis RAB7 homolog RABG3f. E517 interference with VPS35-RABG3f interaction prevents the retromer complex to endosome anchoring, resulting in retention of RABG3f. Using multiple approaches, we show that VPS35-RABG3f-GTP interaction is necessary to trigger downstream events like HOPS complex assembly and fusion of late compartments with the tonoplast. Overall, our results support a role for the interaction of RABG3f-VPS35 as a checkpoint in the control of traffic toward the vacuole.
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38.
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39.
  • Sellgren, Anders, et al. (författare)
  • Pump and pipeline performance when pumping slurries with different particle gradings
  • 2014
  • Ingår i: 19th International Conference on Hydrotransport 2014. - 9781634394444 ; , s. 131-143
  • Konferensbidrag (refereegranskat)abstract
    • A pipeline slurry friction loss model consisting of three regimes was initially proposed by K.C. Wilson in Wilson and Sellgren (2001), then extended to a four components consisting of fluid, pseudo-homogeneous, heterogeneous and fully stratified regimes, Wilson et al. (2006). The weighting technique using up to four regime related components often works well for friction loss estimations based on simple input data and model parameters. This also holds for the ANSI/HI (2011) pump performance derating procedure for settling slurries. The comparisons and discussion focus on coarse particle slurries and some cases where the modelling estimations for pipeline and pump performance were not particularly accurate.--------------------------------------------------------------------------------
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41.
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42.
  • Souza-Moreira, Tatiana M., et al. (författare)
  • Screening of 2A peptides for polycistronic gene expression in yeast
  • 2018
  • Ingår i: FEMS Yeast Research. - : Oxford University Press (OUP). - 1567-1356 .- 1567-1364. ; 18:5
  • Tidskriftsartikel (refereegranskat)abstract
    • A complexity of pathway expression in yeast compared to prokaryotes is the need for separate promoters and terminators for each gene expressed. Single transcript expression and separated protein production is possible via the use of 2A viral peptides, but detailed characterization to assess their suitability and applications is needed. The present work aimed to characterize multiple 2A peptide sequences to determine suitability for metabolic engineering applications in Saccharomyces cerevisiae. We screened 22 peptides placed between fluorescent protein sequences. Cleaving efficiency was calculated by western blot intensity of bands corresponding to the cleaved and uncleaved forms of the reporter. Three out of the 22 sequences showed high cleavage efficiency: 2A peptide from Equine rhinitis B virus (91%), Porcine teschovirus-1 (85%) and Operophtera brumata cypovirus-18 (83%). Furthermore, expression of the released protein was comparable to its monocistronic expression. As a proof-of-concept, the triterpene friedelin was successfully produced in the same yeast strain by expressing its synthase with the truncated form of HMG1 linked by the 2A peptide of ERBV-1, with production titers comparable to monocistronic expression (via separate promoters). These results suggest that these peptides could be suitable for expression and translation of multiple proteins in metabolic engineering applications in S. cerevisiae.
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46.
  • Tobin, John J., et al. (författare)
  • The VLA/ALMA Nascent Disk and Multiplicity (VANDAM) Survey of Orion Protostars. I. Identifying and Characterizing the Protostellar Content of the OMC-2 FIR4 and OMC-2 FIR3 Regions
  • 2019
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 886:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present Atacama Large Millimeter/submillimeter Array (0.87 mm) and Very Large Array (9 mm) observations toward OMC-2 FIR4 and OMC-2 FIR3 within the Orion integral-shaped filament, thought to be two of the nearest regions of intermediate-mass star formation. We characterize the continuum sources within these regions on ?40 au (01) scales and associated molecular line emission at a factor of ?30 better resolution than previous observations at similar wavelengths. We identify six compact continuum sources within OMC-2 FIR4, four in OMC-2 FIR3, and one additional source just outside OMC-2 FIR4. This continuum emission is tracing the inner envelope and/or disk emission on less than 100 au scales. HOPS-108 is the only protostar in OMC-2 FIR4 that exhibits emission from high-excitation transitions of complex organic molecules (e.g., methanol and other lines) coincident with the continuum emission. HOPS-370 in OMC-2 FIR3, with L;?;360 L, also exhibits emission from high-excitation methanol and other lines. The methanol emission toward these two protostars is indicative of temperatures high enough to thermally evaporate it from icy dust grains; overall, these protostars have characteristics similar to hot corinos. We do not identify a clear outflow from HOPS-108 in (CO)-C-12, but we find evidence of interaction between the outflow/jet from HOPS-370 and the OMC-2 FIR4 region. A multitude of observational constraints indicate that HOPS-108 is likely a low- to intermediate-mass protostar in its main mass accretion phase and is the most luminous protostar in OMC-2 FIR4. The high-resolution data presented here are essential for disentangling the embedded protostars from their surrounding dusty environments and characterizing them.
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47.
  • Tobin, John J., et al. (författare)
  • The VLA/ALMA Nascent Disk and Multiplicity (VANDAM) Survey of Orion Protostars. II. A Statistical Characterization of Class 0 and Class i Protostellar Disks
  • 2020
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 890:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We have conducted a survey of 328 protostars in the Orion molecular clouds with the Atacama Large Millimeter/submillimeter Array at 0.87 mm at a resolution of ∼0.″1 (40 au), including observations with the Very Large Array at 9 mm toward 148 protostars at a resolution of ∼0.″08 (32 au). This is the largest multiwavelength survey of protostars at this resolution by an order of magnitude. We use the dust continuum emission at 0.87 and 9 mm to measure the dust disk radii and masses toward the Class 0, Class I, and flat-spectrum protostars, characterizing the evolution of these disk properties in the protostellar phase. The mean dust disk radii for the Class 0, Class I, and flat-spectrum protostars are 44.9-3.4+5.8, 37.0-3.0+4.9, and 28.5-2.3+3.7 au, respectively, and the mean protostellar dust disk masses are 25.9-4.0+7.7, 14.9-2.2+3.8, 11.6-1.9+3.5 M⊙, respectively. The decrease in dust disk masses is expected from disk evolution and accretion, but the decrease in disk radii may point to the initial conditions of star formation not leading to the systematic growth of disk radii or that radial drift is keeping the dust disk sizes small. At least 146 protostellar disks (35% of 379 detected 0.87 mm continuum sources plus 42 nondetections) have disk radii greater than 50 au in our sample. These properties are not found to vary significantly between different regions within Orion. The protostellar dust disk mass distributions are systematically larger than those of Class II disks by a factor of >4, providing evidence that the cores of giant planets may need to at least begin their formation during the protostellar phase.
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