| 1. |
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| 2. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 3. |
- Brown, A. G. A., et al.
(författare)
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Gaia Data Release 1 Summary of the astrometric, photometric, and survey properties
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 595
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Tidskriftsartikel (refereegranskat)abstract
- Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the HIPPARCOS and Tycho-2 catalogues - a realisation of the Tycho-Gaia Astrometric Solution (TGAS) - and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of similar to 3000 Cepheid and RR Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr(-1) for the proper motions. A systematic component of similar to 0.3 mas should be added to the parallax uncertainties. For the subset of similar to 94 000 HIPPARCOS stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr(-1). For the secondary astrometric data set, the typical uncertainty of the positions is similar to 10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to similar to 0.03 mag over the magnitude range 5 to 20.7. Conclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data.
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| 4. |
- Prusti, T., et al.
(författare)
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The Gaia mission
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 595
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Tidskriftsartikel (refereegranskat)abstract
- Gaia is a cornerstone mission in the science programme of the European Space Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page.
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| 5. |
- van Leeuwen, F., et al.
(författare)
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Gaia Data Release 1 : Open cluster astrometry: Performance, limitations, and future prospects
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 601
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Tidskriftsartikel (refereegranskat)abstract
- Context. The first Gaia Data Release contains the Tycho-Gaia Astrometric Solution (TGAS). This is a subset of about 2 million stars for which, besides the position and photometry, the proper motion and parallax are calculated using Hipparcos and Tycho-2 positions in 1991.25 as prior information. Aims. We investigate the scientific potential and limitations of the TGAS component by means of the astrometric data for open clusters. Methods. Mean cluster parallax and proper motion values are derived taking into account the error correlations within the astrometric solutions for individual stars, an estimate of the internal velocity dispersion in the cluster, and, where relevant, the effects of the depth of the cluster along the line of sight. Internal consistency of the TGAS data is assessed. Results. Values given for standard uncertainties are still inaccurate and may lead to unrealistic unit-weight standard deviations of least squares solutions for cluster parameters. Reconstructed mean cluster parallax and proper motion values are generally in very good agreement with earlier Hipparcos-based determination, although the Gaia mean parallax for the Pleiades is a significant exception. We have no current explanation for that discrepancy. Most clusters are observed to extend to nearly 15 pc from the cluster centre, and it will be up to future Gaia releases to establish whether those potential cluster-member stars are still dynamically bound to the clusters. Conclusions. The Gaia DR1 provides the means to examine open clusters far beyond their more easily visible cores, and can provide membership assessments based on proper motions and parallaxes. A combined HR diagram shows the same features as observed before using the Hipparcos data, with clearly increased luminosities for older A and F dwarfs.
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| 6. |
- Clementini, G., et al.
(författare)
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Testing parallaxes with local Cepheids and RR Lyrae stars
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 605
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Tidskriftsartikel (refereegranskat)abstract
- Context. Parallaxes for 331 classical Cepheids, 31 Type II Cepheids, and 364 RR Lyrae stars in common between Gaia and the HIPPARCOS and Tycho-2 catalogues are published in Gaia Data Release 1 (DR1) as part of the Tycho-Gaia Astrometric Solution (TGAS). Aims. In order to test these first parallax measurements of the primary standard candles of the cosmological distance ladder, which involve astrometry collected by Gaia during the initial 14 months of science operation, we compared them with literature estimates and derived new period-luminosity (PL), period-Wesenheit (PW) relations for classical and Type II Cepheids and infrared PL, PL-metallicity (PLZ), and optical luminosity-metallicity (MV-[Fe/H]) relations for the RR Lyrae stars, with zero points based on TGAS.Methods. Classical Cepheids were carefully selected in order to discard known or suspected binary systems. The final sample comprises 102 fundamental mode pulsators with periods ranging from 1.68 to 51.66 days (of which 33 with sigma(omega)/omega < 0 : 5). The Type II Cepheids include a total of 26 W Virginis and BL Herculis stars spanning the period range from 1.16 to 30.00 days (of which only 7 with sigma(omega)/omega 0 : 5). The RR Lyrae stars include 200 sources with pulsation period ranging from 0.27 to 0.80 days (of which 112 with sigma(omega)/omega < 0 : 5). The new relations were computed using multi- band (V; I; J; K-s) photometry and spectroscopic metal abundances available in the literature, and by applying three alternative approaches: (i) linear least-squares fitting of the absolute magnitudes inferred from direct transformation of the TGAS parallaxes; (ii) adopting astrometry-based luminosities; and (iii) using a Bayesian fitting approach. The last two methods work in parallax space where parallaxes are used directly, thus maintaining symmetrical errors and allowing negative parallaxes to be used. The TGAS-based PL; PW; PLZ, and MV [Fe/H] relations are discussed by comparing the distance to the Large Magellanic Cloud provided by different types of pulsating stars and alternative fitting methods.Results. Good agreement is found from direct comparison of the parallaxes of RR Lyrae stars for which both TGAS and HST measurements are available. Similarly, very good agreement is found between the TGAS values and the parallaxes inferred from the absolute magnitudes of Cepheids and RR Lyrae stars analysed with the Baade-Wesselink method. TGAS values also compare favourably with the parallaxes inferred by theoretical model fitting of the multi-band light curves for two of the three classical Cepheids and one RR Lyrae star, which were analysed with this technique in our samples. The K-band PL relations show the significant improvement of the TGAS parallaxes for Cepheids and RR Lyrae stars with respect to the HIPPARCOS measurements. This is particularly true for the RR Lyrae stars for which improvement in quality and statistics is impressive.Conclusions. TGAS parallaxes bring a significant added value to the previous HIPPARCOS estimates. The relations presented in this paper represent the first Gaia-calibrated relations and form a work-in-progress milestone report in the wait for Gaia-only parallaxes of which a first solution will become available with Gaia Data Release 2 (DR2) in 2018.
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| 7. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 8. |
- Chen, T.-W., et al.
(författare)
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SN 2017ens : The Metamorphosis of a Luminous Broadlined Type Ic Supernova into an SN IIn
- 2018
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 867:2
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Tidskriftsartikel (refereegranskat)abstract
- We present observations of supernova (SN) 2017ens, discovered by the ATLAS survey and identified as a hot blue object through the GREAT program. The redshift z = 0.1086 implies a peak brightness of M-g = -21.1 mag, placing the object within the regime of superluminous supernovae. We observe a dramatic spectral evolution, from initially being blue and featureless, to later developing features similar to those of the broadlined Type Ic SN 1998bw, and finally showing 2000 km s(-1) wide H alpha and H beta emission. Relatively narrow Balmer emission (reminiscent of a SN IIn) is present at all times. We also detect coronal lines, indicative of a dense circumstellar medium. We constrain the progenitor wind velocity to similar to 50-60 km s(-1) based on P-Cygni profiles, which is far slower than those present in Wolf-Rayet stars. This may suggest that the progenitor passed through a luminous blue variable phase, or that the wind is instead from a binary companion red supergiant star. At late times we see the similar to 2000 km s(-1) wide H alpha emission persisting at high luminosity (similar to 3 x 10(40) erg s(-1)) for at least 100 day, perhaps indicative of additional mass loss at high velocities that could have been ejected by a pulsational pair instability.
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| 9. |
- Cilliers, S. S., et al.
(författare)
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Garden ecosystem services of Sub-Saharan Africa and the role of health clinic gardens as social-ecological systems
- 2018
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Ingår i: Landscape and Urban Planning. - : Elsevier BV. - 0169-2046 .- 1872-6062. ; 180, s. 294-307
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Tidskriftsartikel (refereegranskat)abstract
- Rapid urbanization is predicted to take place in Africa in the near future and currently stressed cities will be even more overburdened in terms of pressure on green areas and increasing urban poverty. Effectively planning for and conserving current urban green infrastructure will be essential to ensure resilience and maintenance of quality urban environments. Gardens represent major portions of urban green infrastructure. In this paper we review literature to determine the current status of garden ecosystem services under the main themes of provisioning, regulating, supporting and cultural services in sub-Saharan Africa and identify the current challenges in optimizing these ecosystem services. Studying gardens as social-ecological systems might be the key to promote and enhance their resilience capacity in a changing world, acknowledging the fact that gardens are communities of practice in which social learning may occur. Studies on health clinic gardens in the North-West Province of South Africa have indicated how some of the challenges in terms of optimizing garden ecosystem services can be addressed. Multiple stakeholders involved in the health clinic gardens contribute towards a co-production of knowledge that could lead to social learning on aspects such as cultivation of nutritious food. More detailed studies on health clinic gardens are however, necessary to be able to develop a community-based resource management framework that can be implemented in the North-West Province and potentially in other South African provinces and countries in Sub-Saharan Africa.
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| 10. |
- Wahl, Simone, et al.
(författare)
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Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity
- 2017
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Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 541:7635, s. 81-
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type (2) diabetes, cardiovascular disease and related metabolic and inflammatory disturbances(1,2). Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation(3-6), a key regulator of gene expression and molecular phenotype(7). Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 x 10(-7), range P = 9.2 x 10(-8) to 6.0 x 10(-46); n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 x 10(-6), range P = 5.5 x 10(-6) to 6.1 x 10(-35), n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07-2.56); P = 1.1 x 10(-54)). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity.
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| 11. |
- Alvarez-Madrazo, S, et al.
(författare)
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Discontinuation, persistence and adherence to subcutaneous biologics delivered via a homecare route to Scottish adults with rheumatic diseases: a retrospective study
- 2019
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 9:9, s. e027059-
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Tidskriftsartikel (refereegranskat)abstract
- To understand patterns of subcutaneous (SC) biologics use over time in adults with inflammatory rheumatic musculoskeletal diseases receiving a homecare delivery service.DesignRetrospective cohort.SettingPatients in secondary care receiving SC biologics in the largest Scottish Health Board.ParticipantsA new bespoke cohort was created from routine data gathered as part of a health board Homecare Service Database. Patients over 18 years who received a supply of SC biologic from January 2012 to May 2015 with a diagnosis for rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) were included.Outcomes measuredA standardised framework was applied by measuring discontinuation rates, persistence using Kaplan-Meier analysis and Cox regression and adherence using medication refill adherence (MRA) and compliance rate (CR).Results751 patients were identified (AS: 105, PsA: 227, RA: 419) of whom 89.3% had more than one biologic delivery (median days’ follow-up: AS: 494; PsA: 544; RA: 529) and 83.2% did not switch biologic. For all conditions, approximately half were persistent on their index biologic (52% AS, 54% PsA, 48%RA). Of patients who discontinued treatment, the majority reinitiated with the same biologic (19% AS, 18% PsA and 21% RA). Overall adherence during the period of treatment was over 80% when calculated using MRA (median %MRA: AS: 84.0%, PsA: 85.0%, RA: 82.4%) or CR (median %CR: AS: 96.6%, PsA: 97%, RA: 96.6%).ConclusionUse of linked routine data is a sustainable pathway to enable ongoing evaluation of biologics use. A more consistent approach to studying use (discontinuation, persistence and adherence metrics) should be adopted to enable comparability of studies.
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| 12. |
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| 13. |
- Ballester, Facundo, et al.
(författare)
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A generic high-dose rate Ir-192 brachytherapy source for evaluation of model-based dose calculations beyond the TG-43 formalism
- 2015
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Ingår i: Medical physics (Lancaster). - : American Association of Physicists in Medicine: Medical Physics. - 0094-2405. ; 42:6, s. 3048-3062
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: In order to facilitate a smooth transition for brachytherapy dose calculations from the American Association of Physicists in Medicine (AAPM) Task Group No. 43 (TG-43) formalism to model-based dose calculation algorithms (MBDCAs), treatment planning systems (TPSs) using a MBDCA require a set of well-defined test case plans characterized by Monte Carlo (MC) methods. This also permits direct dose comparison to TG-43 reference data. Such test case plans should be made available for use in the software commissioning process performed by clinical end users. To this end, a hypothetical, generic high-dose rate (HDR) Ir-192 source and a virtual water phantom were designed, which can be imported into a TPS. Methods: A hypothetical, generic HDR Ir-192 source was designed based on commercially available sources as well as a virtual, cubic water phantom that can be imported into any TPS in DICOM format. The dose distribution of the generic Ir-192 source when placed at the center of the cubic phantom, and away from the center under altered scatter conditions, was evaluated using two commercial MBDCAs [Oncentra (R) Brachy with advanced collapsed-cone engine (ACE) and BrachyVision AcuRos (TM)]. Dose comparisons were performed using state-of-the-art MC codes for radiation transport, including ALGEBRA, BrachyDose, GEANT4, MCNP5, MCNP6, and pENELopE2008. The methodologies adhered to recommendations in the AAPM TG-229 report on high-energy brachytherapy source dosimetry. TG-43 dosimetry parameters, an along-away dose-rate table, and primary and scatter separated (PSS) data were obtained. The virtual water phantom of (201)(3) voxels (1 mm sides) was used to evaluate the calculated dose distributions. Two test case plans involving a single position of the generic HDR Ir-192 source in this phantom were prepared: (i) source centered in the phantom and (ii) source displaced 7 cm laterally from the center. Datasets were independently produced by different investigators. MC results were then compared against dose calculated using TG-43 and MBDCA methods. Results: TG-43 and PSS datasets were generated for the generic source, the PSS data for use with the ACE algorithm. The dose-rate constant values obtained from seven MC simulations, performed independently using different codes, were in excellent agreement, yielding an average of 1.1109 +/- 0.0004 cGy/(h U) (k = 1, Type A uncertainty). MC calculated dose-rate distributions for the two plans were also found to be in excellent agreement, with differences within type A uncertainties. Differences between commercial MBDCA and MC results were test, position, and calculation parameter dependent. On average, however, these differences were within 1% for ACUROS and 2% for ACE at clinically relevant distances. Conclusions: A hypothetical, generic HDR Ir-192 source was designed and implemented in two commercially available TPSs employing different MBDCAs. Reference dose distributions for this source were benchmarked and used for the evaluation of MBDCA calculations employing a virtual, cubic water phantom in the form of a CT DICOM image series. The implementation of a generic source of identical design in all TPSs using MBDCAs is an important step toward supporting univocal commissioning procedures and direct comparisons between TPSs. (C) 2015 American Association of Physicists in Medicine.
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| 14. |
- Carrillo, I., et al.
(författare)
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Is the Milky Way still breathing? RAVE-Gaia streaming motions
- 2018
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 475:2, s. 2679-2696
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Tidskriftsartikel (refereegranskat)abstract
- We use data from the Radial Velocity Experiment (RAVE) and the Tycho-Gaia astrometric solution (TGAS) catalogue to compute the velocity fields yielded by the radial (V-R), azimuthal (V-phi), and vertical (V-z) components of associated Galactocentric velocity. We search in particular for variation in all three velocity components with distance above and below the disc midplane, as well as how each component of V-z (line-of-sight and tangential velocity projections) modifies the obtained vertical structure. To study the dependence of velocity on proper motion and distance, we use two main samples: a RAVE sample including proper motions from the Tycho-2, PPMXL, and UCAC4 catalogues, and a RAVE-TGAS sample with inferred distances and proper motions from the TGAS and UCAC5 catalogues. In both samples, we identify asymmetries in V-R and V-z. Below the plane, we find the largest radial gradient to be partial derivative V-R/partial derivative R = -7.01 +/- 0.61 km s(-1) kpc(-1), in agreement with recent studies. Above the plane, we find a similar gradient with partial derivative V-R/partial derivative R = -9.42 +/- 1.77 km s(-1) kpc(-1). By comparing our results with previous studies, we find that the structure in V-z is strongly dependent on the adopted proper motions. Using the Galaxia Milky Way model, we demonstrate that distance uncertainties can create artificial wave-like patterns. In contrast to previous suggestions of a breathing mode seen in RAVE data, our results support a combination of bending and breathing modes, likely generated by a combination of external or internal and external mechanisms.
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| 15. |
- Gomez-Blanco, J., et al.
(författare)
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Using Scipion for stream image processing at Cryo-EM facilities
- 2018
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Ingår i: Journal of Structural Biology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1047-8477 .- 1095-8657. ; 204:3, s. 457-463
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Tidskriftsartikel (refereegranskat)abstract
- Three dimensional electron microscopy is becoming a very data-intensive field in which vast amounts of experimental images are acquired at high speed. To manage such large-scale projects, we had previously developed a modular workflow system called Scipion (de la Rosa-Trevfn et al., 2016). We present here a major extension of Scipion that allows processing of EM images while the data is being acquired. This approach helps to detect problems at early stages, saves computing time and provides users with a detailed evaluation of the data quality before the acquisition is finished. At present, Scipion has been deployed and is in production mode in seven Cryo-EM facilities throughout the world.
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| 16. |
- Lehnert, Kristina, et al.
(författare)
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Cytokine expression and lymphocyte proliferative capacity in diseased harbor porpoises (Phocoena phocoena) - Biomarkers for health assessment in wildlife cetaceans
- 2019
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Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491 .- 1873-6424. ; 247, s. 783-791
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Tidskriftsartikel (refereegranskat)abstract
- Harbor porpoises (Phocoena phocoena) in the North and Baltic Seas are exposed to anthropogenic influences including acoustic stress and environmental contaminants. In order to evaluate immune responses in healthy and diseased harbor porpoise cells, cytokine expression analyses and lymphocyte proliferation assays, together with toxicological analyses were performed in stranded and bycaught animals as well as in animals kept in permanent human care. Severely diseased harbor porpoises showed a reduced proliferative capacity of peripheral blood lymphocytes together with diminished transcription of transforming growth factor-beta and tumor necrosis factor-alpha compared to healthy controls. Toxicological analyses revealed accumulation of polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), and dichlorodiphenyltrichloroethane (DDT) in harbor porpoise blood samples. Correlation analyses between blood organochlorine levels and immune parameters revealed no direct effects of xenobiotics upon lymphocyte proliferation or cytokine transcription, respectively. Results reveal an impaired function of peripheral blood leukocytes in severely diseased harbor porpoises, indicating immune exhaustion and increased disease susceptibility.
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| 17. |
- Ma, Yunzhi, et al.
(författare)
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A generic TG-186 shielded applicator for commissioning model-based dose calculation algorithms for high-dose-rate Ir-192 brachytherapy
- 2017
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Ingår i: Medical physics (Lancaster). - : WILEY. - 0094-2405 .- 2473-4209. ; 44:11, s. 5961-5976
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Tidskriftsartikel (refereegranskat)abstract
- PurposeA joint working group was created by the American Association of Physicists in Medicine (AAPM), the European Society for Radiotherapy and Oncology (ESTRO), and the Australasian Brachytherapy Group (ABG) with the charge, among others, to develop a set of well-defined test case plans and perform calculations and comparisons with model-based dose calculation algorithms (MBDCAs). Its main goal is to facilitate a smooth transition from the AAPM Task Group No. 43 (TG-43) dose calculation formalism, widely being used in clinical practice for brachytherapy, to the one proposed by Task Group No. 186 (TG-186) for MBDCAs. To do so, in this work a hypothetical, generic high-dose rate (HDR) Ir-192 shielded applicator has been designed and benchmarked. MethodsA generic HDR Ir-192 shielded applicator was designed based on three commercially available gynecological applicators as well as a virtual cubic water phantom that can be imported into any DICOM-RT compatible treatment planning system (TPS). The absorbed dose distribution around the applicator with the TG-186 Ir-192 source located at one dwell position at its center was computed using two commercial TPSs incorporating MBDCAs (Oncentra((R)) Brachy with Advanced Collapsed-cone Engine, ACE, and BrachyVision ACUROS) and state-of-the-art Monte Carlo (MC) codes, including ALGEBRA, BrachyDose, egs_brachy, Geant4, MCNP6, and Penelope2008. TPS-based volumetric dose distributions for the previously reported source centered in water and source displaced test cases, and the new source centered in applicator test case, were analyzed here using the MCNP6 dose distribution as a reference. Volumetric dose comparisons of TPS results against results for the other MC codes were also performed. Distributions of local and global dose difference ratios are reported. ResultsThe local dose differences among MC codes are comparable to the statistical uncertainties of the reference datasets for the source centered in water and source displaced test cases and for the clinically relevant part of the unshielded volume in the source centered in applicator case. Larger local differences appear in the shielded volume or at large distances. Considering clinically relevant regions, global dose differences are smaller than the local ones. The most disadvantageous case for the MBDCAs is the one including the shielded applicator. In this case, ACUROS agrees with MC within [-4.2%, +4.2%] for the majority of voxels (95%) while presenting dose differences within [-0.12%, +0.12%] of the dose at a clinically relevant reference point. For ACE, 95% of the total volume presents differences with respect to MC in the range [-1.7%, +0.4%] of the dose at the reference point. ConclusionsThe combination of the generic source and generic shielded applicator, together with the previously developed test cases and reference datasets (available in the Brachytherapy Source Registry), lay a solid foundation in supporting uniform commissioning procedures and direct comparisons among treatment planning systems for HDR Ir-192 brachytherapy.
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| 18. |
- Zhang, R. Y., et al.
(författare)
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Lysozyme's lectin-like characteristics facilitates its immune defense function
- 2017
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Ingår i: Quarterly Reviews of Biophysics. - : Cambridge University Press (CUP). - 0033-5835 .- 1469-8994. ; 50, s. 1-12
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Forskningsöversikt (refereegranskat)abstract
- Interactions between human lysozyme (HL) and the lipopolysaccharide (LPS) of Klebsiella pneumoniae O1, a causative agent of lung infection, were identified by surface plasmon resonance. To characterize the molecular mechanism of this interaction, HL binding to synthetic disaccharides and tetrasaccharides representing one and two repeating units, respectively, of the O-chain of this LPS were studied. pH-dependent structural rearrangements of HL after interaction with the disaccharide were observed through nuclear magnetic resonance. The crystal structure of the HL-tetrasaccharide complex revealed carbohydrate chain packing into the A, B, C, and D binding sites of HL, which primarily occurred through residue-specific, direct or water-mediated hydrogen bonds and hydrophobic contacts. Overall, these results support a crucial role of the Glu35/Asp53/Trp63/Asp102 residues in HL binding to the tetrasaccharide. These observations suggest an unknown glycan-guided mechanism that underlies recognition of the bacterial cell wall by lysozyme and may complement the HL immune defense function.
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