| 1. |
- Coustenis, A., et al.
(författare)
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TandEM : Titan and Enceladus mission
- 2009
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 23:3, s. 893-946
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Tidskriftsartikel (refereegranskat)abstract
- TandEM was proposed as an L-class (large) mission in response to ESA's Cosmic Vision 2015-2025 Call, and accepted for further studies, with the goal of exploring Titan and Enceladus. The mission concept is to perform in situ investigations of two worlds tied together by location and properties, whose remarkable natures have been partly revealed by the ongoing Cassini-Huygens mission. These bodies still hold mysteries requiring a complete exploration using a variety of vehicles and instruments. TandEM is an ambitious mission because its targets are two of the most exciting and challenging bodies in the Solar System. It is designed to build on but exceed the scientific and technological accomplishments of the Cassini-Huygens mission, exploring Titan and Enceladus in ways that are not currently possible (full close-up and in situ coverage over long periods of time). In the current mission architecture, TandEM proposes to deliver two medium-sized spacecraft to the Saturnian system. One spacecraft would be an orbiter with a large host of instruments which would perform several Enceladus flybys and deliver penetrators to its surface before going into a dedicated orbit around Titan alone, while the other spacecraft would carry the Titan in situ investigation components, i.e. a hot-air balloon (MontgolfiSre) and possibly several landing probes to be delivered through the atmosphere.
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| 4. |
- Dorigo, Wouter, et al.
(författare)
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The International Soil Moisture Network : Serving Earth system science for over a decade
- 2021
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Ingår i: Hydrology and Earth System Sciences. - : Copernicus GmbH. - 1027-5606 .- 1607-7938. ; 25:11, s. 5749-5804
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Forskningsöversikt (refereegranskat)abstract
- In 2009, the International Soil Moisture Network (ISMN) was initiated as a community effort, funded by the European Space Agency, to serve as a centralised data hosting facility for globally available in situ soil moisture measurements . The ISMN brings together in situ soil moisture measurements collected and freely shared by a multitude of organisations, harmonises them in terms of units and sampling rates, applies advanced quality control, and stores them in a database. Users can freely retrieve the data from this database through an online web portal (https://ismn.earth/en/, last access: 28 October 2021). Meanwhile, the ISMN has evolved into the primary in situ soil moisture reference database worldwide, as evidenced by more than 3000 active users and over 1000 scientific publications referencing the data sets provided by the network. As of July 2021, the ISMN now contains the data of 71 networks and 2842 stations located all over the globe, with a time period spanning from 1952 to the present. The number of networks and stations covered by the ISMN is still growing, and approximately 70 % of the data sets contained in the database continue to be updated on a regular or irregular basis. The main scope of this paper is to inform readers about the evolution of the ISMN over the past decade, including a description of network and data set updates and quality control procedures. A comprehensive review of the existing literature making use of ISMN data is also provided in order to identify current limitations in functionality and data usage and to shape priorities for the next decade of operations of this unique community-based data repository.
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| 5. |
- Jones, Robert P., et al.
(författare)
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Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma : A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial
- 2019
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Ingår i: JAMA Surgery. - : AMER MEDICAL ASSOC. - 2168-6254 .- 2168-6262. ; 154:11, s. 1038-1048
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Tidskriftsartikel (refereegranskat)abstract
- Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.Design, Setting, and Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.Results: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P=.03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P=.04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P=.27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P=.85 and P=.35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P=.03).Conclusions and Relevance: There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.Trial Registration: ClinicalTrials.gov identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434. This secondary analysis of a randomized clinical trial investigates patterns of recurrence after adjuvant chemotherapy in pancreatic cancer and the association with survival.
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| 9. |
- Vigren, E., et al.
(författare)
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On the thermal electron balance in Titan's sunlit upper atmosphere
- 2013
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Ingår i: Icarus. - : Elsevier BV. - 0019-1035 .- 1090-2643. ; 223:1, s. 234-251
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Tidskriftsartikel (refereegranskat)abstract
- The Cassini mission has investigated Titan's upper atmosphere in detail and found that, under solar irradiation, it has a well-developed ionosphere, which peaks between 1000 and 1200km. In this paper we focus on the T40, T41, T42 and T48 Titan flybys by the Cassini spacecraft and use in situ measurements of N2 and CH4 densities by the Ion Neutral Mass Spectrometer (INMS) as input into a solar energy deposition model to determine electron production rates. We combine these electron production rates with estimates of the effective recombination coefficient based on available laboratory data for Titan ions' dissociative recombination rates and electron temperatures derived from the Langmuir probe (LP) to predict electron number densities in Titan's upper atmosphere, assuming photochemical equilibrium and loss of electrons exclusively through dissociative recombination with molecular ions. We then compare these predicted electron number densities with those observed in Titan's upper atmosphere by the LP. The assumption of photochemical equilibrium is supported by a reasonable agreement between the altitudes where the electron densities are observed to peak and where the electron production rates are calculated to peak (roughly corresponding to the unit optical depth for HeII photons at 30.38nm). We find, however, that the predicted electron number densities are nearly a factor of two higher than those observed throughout the altitude range between 1050 and 1200km (where we have made estimates of the effective recombination coefficient). There are different possible reasons for this discrepancy; one possibility is that there may be important loss processes of free electrons other than dissociative recombination in Titan's upper atmosphere.
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| 14. |
- Ghaneh, Paula, et al.
(författare)
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The Impact of Positive Resection Margins on Survival and Recurrence Following Resection and Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma
- 2019
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Ingår i: Annals of Surgery. - 0003-4932 .- 1528-1140. ; 269:3, s. 520-529
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Tidskriftsartikel (refereegranskat)abstract
- Objective and Background: Local and distant disease recurrence are frequently observed following pancreatic cancer resection, but an improved understanding of resection margin assessment is required to aid tailored therapiesMethods: Analyses were carried out to assess the association between clinical characteristics and margin involvement as well as the effects of individual margin involvement on site of recurrence and overall and recurrence-free survival using individual patient data from the European Study Group for Pancreatic Cancer (ESPAC)-3 randomized controlled trial.Results: There were 1151 patients, of whom 505 (43.9%) had an RI resection. The median and 95% confidence interval (CI) overall survival was 24.9 (22.9-27.2) months for 646 (56.1%) patients with resection margin negative R0 >1 mm) tumors, 25.4 (21.6 30.4) months for 146 (12.7%) patients with RI <1 mm positive resection margins, and 18.7 (17.2-21.1) months for 359 (31.2%) patients with R1-direct positive margins (P < 0.001). In multivariable analysis, overall R 1-direct tumor margins, poor tumor differentiation, positive lymph node status, WHO performance status ≥ 1, maximum tumor size, and RI-direct posterior resection margin were all independently significantly associated with reduced overall and recurrence-free survival. Competing risks analysis showed that overall R1-direct positive resection margin status, positive lymph node status. WHO performance status 1, and R1-direct positive superior mesenteric/medial margin resection status were all significantly associated with local recurrence.Conclusions: RI-direct resections were associated with significantly reduced overall and recurrence-free survival following pancreatic cancer resection. Resection margin involvement was also associated with an increased risk for local recurrence.
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| 15. |
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| 17. |
- Greinacher, A, et al.
(författare)
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Heparin-induced thrombocytopenia : a prospective study on the incidence, platelet-activating capacity and clinical significance of antiplatelet factor 4/heparin antibodies of the IgG, IgM, and IgA classes.
- 2007
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 5:8, s. 1666-73
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Platelet-activating antiplatelet factor 4/heparin (anti-PF4/heparin) antibodies are the major cause of heparin-induced thrombocytopenia (HIT). However, the relative utility of functional (platelet activation) vs. antigen [enzyme-immunoassay (EIA)] assays, and the significance of assay discrepancies remain unresolved. METHODS: Consecutive patient sera (n = 1650) referred for diagnostic HIT testing were screened prospectively by both the heparin-induced platelet activation (HIPA) test and anti-PF4/heparin EIA - including individual classes (IgG, IgA, IgM) - with clinical correlations studied. Platelet microparticle and annexin-V-binding properties of the sera were also investigated. RESULTS: Only 205 (12.4%) sera tested positive in either the HIPA and/or EIA: 95 (46.3%) were positive in both, 109 (53.1%) were only EIA-positive, and, notably, only one serum was HIPA-positive/EIA-negative. Of 185 EIA-positive sera, only 17.6% had detectable IgM and/or IgA without detectable IgG. Among sera positive for EIA IgG, optical density values were higher when the sera were HIPA-positive (1.117 vs. 0.768; P < 0.0001), with widely overlapping values. Two HIPA-positive but EIA-IgG-negative sera became HIPA-negative following IgG depletion, suggesting platelet-activating antibodies against non-PF4-dependent antigens. Clinical correlations showed that HIPA-negative/EIA-positive patients did not develop thrombosis and had reasons other than HIT to explain thrombocytopenia. IgM/A antibodies did not increase microparticle penetration, but increased annexin-V binding. CONCLUSIONS: The anti-PF4/heparin EIA has high ( approximately 99%) sensitivity for HIT. However, only about half of EIA-positive patients are likely to have HIT. Anti-PF4/heparin antibodies of IgM/A class and non-PF4-dependent antigens have only a minor role in HIT.
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| 18. |
- Jones, G. H., et al.
(författare)
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The dust halo of Saturn's largest icy moon, Rhea
- 2008
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 319:5868, s. 1380-1384
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Tidskriftsartikel (refereegranskat)abstract
- Saturn's moon Rhea had been considered massive enough to retain a thin, externally generated atmosphere capable of locally affecting Saturn's magnetosphere. The Cassini spacecraft's in situ observations reveal that energetic electrons are depleted in the moon's vicinity. The absence of a substantial exosphere implies that Rhea's magnetospheric interaction region, rather than being exclusively induced by sputtered gas and its products, likely contains solid material that can absorb magnetospheric particles. Combined observations from several instruments suggest that this material is in the form of grains and boulders up to several decimetres in size and orbits Rhea as an equatorial debris disk. Within this disk may reside denser, discrete rings or arcs of material.
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| 19. |
- Rodriguez, Sébastien, et al.
(författare)
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Science goals and new mission concepts for future exploration of Titan's atmosphere, geology and habitability : titan POlar scout/orbitEr and in situ lake lander and DrONe explorer (POSEIDON)
- 2022
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 54:2-3, s. 911-973
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Tidskriftsartikel (refereegranskat)abstract
- In response to ESA’s “Voyage 2050” announcement of opportunity, we propose an ambitious L-class mission to explore one of the most exciting bodies in the Solar System, Saturn’s largest moon Titan. Titan, a “world with two oceans”, is an organic-rich body with interior-surface-atmosphere interactions that are comparable in complexity to the Earth. Titan is also one of the few places in the Solar System with habitability potential. Titan’s remarkable nature was only partly revealed by the Cassini-Huygens mission and still holds mysteries requiring a complete exploration using a variety of vehicles and instruments. The proposed mission concept POSEIDON (Titan POlar Scout/orbitEr and In situ lake lander DrONe explorer) would perform joint orbital and in situ investigations of Titan. It is designed to build on and exceed the scope and scientific/technological accomplishments of Cassini-Huygens, exploring Titan in ways that were not previously possible, in particular through full close-up and in situ coverage over long periods of time. In the proposed mission architecture, POSEIDON consists of two major elements: a spacecraft with a large set of instruments that would orbit Titan, preferably in a low-eccentricity polar orbit, and a suite of in situ investigation components, i.e. a lake lander, a “heavy” drone (possibly amphibious) and/or a fleet of mini-drones, dedicated to the exploration of the polar regions. The ideal arrival time at Titan would be slightly before the next northern Spring equinox (2039), as equinoxes are the most active periods to monitor still largely unknown atmospheric and surface seasonal changes. The exploration of Titan’s northern latitudes with an orbiter and in situ element(s) would be highly complementary in terms of timing (with possible mission timing overlap), locations, and science goals with the upcoming NASA New Frontiers Dragonfly mission that will provide in situ exploration of Titan’s equatorial regions, in the mid-2030s.
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| 20. |
- Rosenqvist, Lisa, et al.
(författare)
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Titan ionospheric conductivities from Cassini measurements
- 2009
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Ingår i: Planetary and Space Science. - : Elsevier BV. - 0032-0633 .- 1873-5088. ; 57:14-15, s. 1828-1833
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Tidskriftsartikel (refereegranskat)abstract
- We present the first results of ionospheric conductivities at Titan based on measurements during 17 Titan flybys from the Cassini spacecraft. We identify an ionospheric region ranging from 1450 95 km (approximately the location of the exobase) to approximately 1000 km where electrical currents perpendicular to the magnetic field may become important. In this region the ionosphere is highly conductive with peak Pedersen conductivities of 0.002-0.05 S/m and peak Hall conductivities of 0.01-0.3 S/m depending on Solar illumination and magnetospheric conditions. Ionospheric conductivities are found to be typically higher on the sunlit side of Titan. However, Hall and Pedersen conductivities depend strongly on the magnetic field magnitude which is highly variable, both in altitude and with respect to the draping configuration of Saturn's magnetic field around Titan. Furthermore, a consistent double peak nature is found in the altitude profile of the Pedersen conductivity. A high altitude peak is found to be located between 1300 and 1400 km. A second and typically more conductive region is observed below 1000 km, where the magnetic field strength drops sharply while the electron density still remains high. This nature of the Pedersen conductivity profile may give rise to complicated ionospheric-atmospheric dynamics and may be expected also at other unmagnetized objects with a substantial atmosphere, such as e.g. Mars and Venus. Estimates of the total Pedersen conductance are found to range between 1300 and 22,000 S. The Pedersen conductance is always higher than the local Alfven conductance but the difference varies by two orders of magnitude (from a factor 4 to 100). Thus, the conditions for reflection or absorption of Alfven waves in Titans ionosphere are highly variable and depends strongly on the magnetic field strength.
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| 21. |
- Roth, Lorenz, et al.
(författare)
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Constraints on an exosphere at Ceres from Hubble Space Telescope observations
- 2016
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Ingår i: Geophysical Research Letters. - : Blackwell Publishing. - 0094-8276 .- 1944-8007. ; 43:6, s. 2465-2472
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Tidskriftsartikel (refereegranskat)abstract
- We report far ultraviolet observations of Ceres obtained with the Cosmic Origin Spectrograph (COS) of the Hubble Space Telescope in the search for atomic emissions from an exosphere. The derived brightnesses at the oxygen lines at 1304 Å and 1356 Å are consistent with zero signals within the 1σ propagated statistical uncertainties. The OI 1304 Å brightness of 0.12 ± 0.20 Rayleighs can be explained by solar resonant scattering from an atomic oxygen column density of (8.2 ± 13.4) × 1010 cm-2. Assuming that O is produced by photodissociation of H2O, we derive an upper limit for H2O abundance and compare it to previous observations. Our upper limit is well above the expected O brightness for a tenuous sublimated H2O exosphere, but it suggests that H2O production with a rate higher than 4 × 1026 molecules s-1 was not present at the time of the COS observation. Additionally, we derive an extremely low geometric albedo of ∼1% in the 1300 Å to 1400 Å range.
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| 22. |
- Roth, Lorenz, et al.
(författare)
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Europa's far ultraviolet oxygen aurora from a comprehensive set of HST observations
- 2016
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Ingår i: Journal of Geophysical Research - Space Physics. - : Blackwell Publishing. - 2169-9380 .- 2169-9402. ; 121:3, s. 2143-2170
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Tidskriftsartikel (refereegranskat)abstract
- We analyze a large set of far ultraviolet oxygen aurora images of Europa's atmosphere taken by Hubble's Space Telescope Imaging Spectrograph (HST/STIS) in 1999 and on 19 occasions between 2012 and 2015. We find that both brightness and aurora morphology undergo systematic variations correlated to the periodically changing plasma environment. The time variable morphology seems to be strongly affected by Europa's interaction with the magnetospheric plasma. The brightest emissions are often found in the polar region where the ambient Jovian magnetic field line is normal to Europa's disk. Near the equator, where bright spots are found at Io, Europa's aurora is faint suggesting a general difference in how the plasma interaction shapes the aurora at Io and Europa. The dusk side is consistently brighter than the dawnside with only few exceptions, which cannot be readily explained by obvious plasma physical or known atmospheric effects. Brightness ratios of the near-surface OI] 1356 Å to OI 1304 Å emissions between 1.5 and 2.8 with a mean ratio of 2.0 are measured, confirming that Europa's bound atmosphere is dominated by O2. The 1356/1304 ratio decreases with increasing altitude in agreement with a more extended atomic O corona, but O2 prevails at least up to altitudes of ∼900 km. Differing 1356/1304 line ratios on the plasma upstream and downstream hemispheres are explained by a differing O mixing ratio in the near-surface O2 atmosphere of ∼5% (upstream) and ≲1% (downstream), respectively. During several eclipse observations, the aurora does not reveal any signs of systematic changes compared to the sunlit images suggesting no or only weak influence of sunlight on the aurora and an optically thin atmosphere.
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| 23. |
- Saur, J., et al.
(författare)
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The search for a subsurface ocean in Ganymede with Hubble Space Telescope observations of its auroral ovals
- 2015
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Ingår i: Journal of Geophysical Research - Space Physics. - : Blackwell Publishing. - 2169-9380 .- 2169-9402. ; 120:3, s. 1715-1737
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Tidskriftsartikel (refereegranskat)abstract
- We present a new approach to search for a subsurface ocean within Ganymede through observations and modeling of the dynamics of its auroral ovals. The locations of the auroral ovals oscillate due to Jupiter's time-varying magnetospheric field seen in the rest frame of Ganymede. If an electrically conductive ocean is present, the external time-varying magnetic field is reduced due to induction within the ocean and the oscillation amplitude of the ovals decreases. Hubble Space Telescope (HST) observations show that the locations of the ovals oscillate on average by 2.0 ±1.3. Our model calculations predict a significantly stronger oscillation by 5.8 ± 1.3 without ocean compared to 2.2±1.3 if an ocean is present. Because the ocean and the no-ocean hypotheses cannot be separated by simple visual inspection of individual HST images, we apply a statistical analysis including a Monte Carlo test to also address the uncertainty caused by the patchiness of observed emissions. The observations require a minimum electrical conductivity of 0.09 S/m for an ocean assumed to be located between 150 km and 250 km depth or alternatively a maximum depth of the top of the ocean at 330 km. Our analysis implies that Ganymede's dynamo possesses an outstandingly low quadrupole-to-dipole moment ratio. The new technique applied here is suited to probe the interior of other planetary bodies by monitoring their auroral response to time-varying magnetic fields. Key Points New technique to search for a subsurface ocean in Ganymede with a telescope Ocean affects auroral oscillation caused by time-varying external magnetic field HST observations reveal weak auroral oscillation and imply existence of ocean
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| 24. |
- Schamai, Wladimir, et al.
(författare)
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Execution of UML state machines using modelica
- 2010
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Ingår i: Proceedings of the 3rd International Workshop on Equation-Based Object-Oriented Modeling Languages and Tools, EOOLT 2010 - In Conjunction with MODELS 2010. - : Linköping University Electronic Press. - 9789175198248 ; , s. 1-10
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Konferensbidrag (refereegranskat)abstract
- ModelicaML is a UML profile for the creation of executable models. ModelicaML supports the Model-Based Systems Engineering (MBSE) paradigm and combines the power of the OMG UML standardized graphical notation for systems and software modeling, and the simulation power of Modelica. This addresses the increasing need for precise integrated modeling of products containing both software and hardware. This paper focuses on the implementation of executable UML state machines in ModelicaML and demonstrates that using Modelica as an action language enables the integrated modeling and simulation of continuous-time and reactive or event-based system dynamics. More specifically, this paper highlights issues that are identified in the UML specification and that are experienced with typical executable implementations of UML state machines. The issues identified are resolved and rationales for design decisions taken are discussed.
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| 29. |
- Walsh, Naomi, et al.
(författare)
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Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer
- 2019
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 111:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes.Methods: We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided.Results: We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P ≤ 1.3 × 10-5), the strongest associations were detected in five pathways and gene sets, including maturity-onset diabetes of the young, regulation of beta-cell development, role of epidermal growth factor (EGF) receptor transactivation by G protein-coupled receptors in cardiac hypertrophy pathways, and the Nikolsky breast cancer chr17q11-q21 amplicon and Pujana ATM Pearson correlation coefficient (PCC) network gene sets. We identified and validated rs876493 and three correlating SNPs (PGAP3) and rs3124737 (CASP7) from the Pujana ATM PCC gene set as eQTLs in two normal derived pancreas tissue datasets.Conclusion: Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.
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| 30. |
- Waterton, John C., et al.
(författare)
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Repeatability and reproducibility of longitudinal relaxation rate in 12 small-animal MRI systems
- 2019
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Ingår i: Magnetic Resonance Imaging. - : Elsevier BV. - 1873-5894 .- 0730-725X. ; 59, s. 121-129
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many translational MR biomarkers derive from measurements of the water proton longitudinal relaxation rate R 1 , but evidence for between-site reproducibility of R 1 in small-animal MRI is lacking. Objective: To assess R 1 repeatability and multi-site reproducibility in phantoms for preclinical MRI. Methods: R 1 was measured by saturation recovery in 2% agarose phantoms with five nickel chloride concentrations in 12 magnets at 5 field strengths in 11 centres on two different occasions within 1–13 days. R 1 was analysed in three different regions of interest, giving 360 measurements in total. Root-mean-square repeatability and reproducibility coefficients of variation (CoV) were calculated. Propagation of reproducibility errors into 21 translational MR measurements and biomarkers was estimated. Relaxivities were calculated. Dynamic signal stability was also measured. Results: CoV for day-to-day repeatability (N = 180 regions of interest) was 2.34% and for between-centre reproducibility (N = 9 centres) was 1.43%. Mostly, these do not propagate to biologically significant between-centre error, although a few R 1 -based MR biomarkers were found to be quite sensitive even to such small errors in R 1 , notably in myocardial fibrosis, in white matter, and in oxygen-enhanced MRI. The relaxivity of aqueous Ni 2+ in 2% agarose varied between 0.66 s −1 mM −1 at 3 T and 0.94 s −1 mM −1 at 11.7T. Interpretation: While several factors affect the reproducibility of R 1 -based MR biomarkers measured preclinically, between-centre propagation of errors arising from intrinsic equipment irreproducibility should in most cases be small. However, in a few specific cases exceptional efforts might be required to ensure R 1 -reproducibility.
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| 31. |
- Zhang, Mingfeng, et al.
(författare)
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Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:41, s. 66328-66343
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10(-15)), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10(-9)) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10(-8)). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L-TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10(-8)). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10(-4)-2.0x10(-3)). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.
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