| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
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| 3. |
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| 4. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Thoma, B, et al.
(författare)
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An international, interprofessional investigation of the self-reported podcast listening habits of emergency clinicians: A METRIQ Study
- 2020
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Ingår i: CJEM. - : Springer Science and Business Media LLC. - 1481-8043 .- 1481-8035. ; 22:1, s. 112-117
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesPodcasts are increasingly being used for medical education. A deeper understanding of usage patterns would inform both producers and researchers of medical podcasts. We aimed to determine how and why podcasts are used by emergency medicine and critical care clinicians.MethodsAn international interprofessional sample (medical students, residents, physicians, nurses, physician assistants, and paramedics) was recruited through direct contact and a multimodal social media (Twitter and Facebook) campaign. Each participant completed a survey outlining how and why they utilize medical podcasts. Recruitment materials included an infographic and study website.Results390 participants from 33 countries and 4 professions (medicine, nursing, paramedicine, physician assistant) completed the survey. Participants most frequently listened to medical podcasts to review new literature (75.8%), learn core material (75.1%), and refresh memory (71.8%). The majority (62.6%) were aware of the ability to listen at increased speeds, but most (76.9%) listened at 1.0 x (normal) speed. All but 25 (6.4%) participants concurrently performed other tasks while listening. Driving (72.3%), exercising (39.7%), and completing chores (39.2%) were the most common. A minority of participants used active learning techniques such as pausing, rewinding, and replaying segments of the podcast. Very few listened to podcasts multiple times.ConclusionsAn international cohort of emergency clinicians use medical podcasts predominantly for learning. Their listening habits (rarely employing active learning strategies and frequently performing concurrent tasks) may not support this goal. Further exploration of the impact of these activities on learning from podcasts is warranted.
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| 9. |
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| 10. |
- Reimerdes, H., et al.
(författare)
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Overview of the TCV tokamak experimental programme
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- The tokamak a configuration variable (TCV) continues to leverage its unique shaping capabilities, flexible heating systems and modern control system to address critical issues in preparation for ITER and a fusion power plant. For the 2019-20 campaign its configurational flexibility has been enhanced with the installation of removable divertor gas baffles, its diagnostic capabilities with an extensive set of upgrades and its heating systems with new dual frequency gyrotrons. The gas baffles reduce coupling between the divertor and the main chamber and allow for detailed investigations on the role of fuelling in general and, together with upgraded boundary diagnostics, test divertor and edge models in particular. The increased heating capabilities broaden the operational regime to include T (e)/T (i) similar to 1 and have stimulated refocussing studies from L-mode to H-mode across a range of research topics. ITER baseline parameters were reached in type-I ELMy H-modes and alternative regimes with 'small' (or no) ELMs explored. Most prominently, negative triangularity was investigated in detail and confirmed as an attractive scenario with H-mode level core confinement but an L-mode edge. Emphasis was also placed on control, where an increased number of observers, actuators and control solutions became available and are now integrated into a generic control framework as will be needed in future devices. The quantity and quality of results of the 2019-20 TCV campaign are a testament to its successful integration within the European research effort alongside a vibrant domestic programme and international collaborations.
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| 11. |
- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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| 12. |
- Chellaï, O., et al.
(författare)
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Millimeter-wave beam scattering and induced broadening by plasma turbulence in the TCV tokamak
- 2021
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 61:6
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Tidskriftsartikel (refereegranskat)abstract
- The scattering of millimeter-wave beams from electron density fluctuations and the associated beam broadening are experimentally demonstrated. Using a dedicated setup, instantaneous deflection and (de-)focusing of the beam due to density blobs on the beam path are shown to agree with full-wave simulations. The detected time-averaged wave power transmitted through the turbulent plasma is reproduced by the radiative-transfer model implemented in the WKBeam code, which predicts a ∼50% turbulence-induced broadening of the beam cross-section. The role of core turbulence for the considered geometry is highlighted.
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| 13. |
- Khatri, B., et al.
(författare)
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Genome-wide association study identifies Sjogren's risk loci with functional implications in immune and glandular cells
- 2022
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Sjogren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjogren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjogren's syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.
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| 14. |
- Falster, Daniel, et al.
(författare)
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AusTraits, a curated plant trait database for the Australian flora
- 2021
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Ingår i: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge.
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| 15. |
- Charette, M. A., et al.
(författare)
-
The Transpolar Drift as a Source of Riverine and Shelf-Derived Trace Elements to the Central Arctic Ocean
- 2020
-
Ingår i: Journal of Geophysical Research-Oceans. - : American Geophysical Union (AGU). - 2169-9275 .- 2169-9291. ; 125:5
-
Tidskriftsartikel (refereegranskat)abstract
- A major surface circulation feature of the Arctic Ocean is the Transpolar Drift (TPD), a current that transports river-influenced shelf water from the Laptev and East Siberian Seas toward the center of the basin and Fram Strait. In 2015, the international GEOTRACES program included a high-resolution pan-Arctic survey of carbon, nutrients, and a suite of trace elements and isotopes (TEIs). The cruises bisected the TPD at two locations in the central basin, which were defined by maxima in meteoric water and dissolved organic carbon concentrations that spanned 600 km horizontally and similar to 25-50 m vertically. Dissolved TEIs such as Fe, Co, Ni, Cu, Hg, Nd, and Th, which are generally particle-reactive but can be complexed by organic matter, were observed at concentrations much higher than expected for the open ocean setting. Other trace element concentrations such as Al, V, Ga, and Pb were lower than expected due to scavenging over the productive East Siberian and Laptev shelf seas. Using a combination of radionuclide tracers and ice drift modeling, the transport rate for the core of the TPD was estimated at 0.9 +/- 0.4 Sv (10(6) m(3)s(-1)). This rate was used to derive the mass flux for TEIs that were enriched in the TPD, revealing the importance of lateral transport in supplying materials beneath the ice to the central Arctic Ocean and potentially to the North Atlantic Ocean via Fram Strait. Continued intensification of the Arctic hydrologic cycle and permafrost degradation will likely lead to an increase in the flux of TEIs into the Arctic Ocean. Plain Language Summary A major feature of the Arctic Ocean circulation is the Transpolar Drift (TPD), a surface current that carries ice and continental shelf-derived materials from Siberia across the North Pole to the North Atlantic Ocean. In 2015, an international team of oceanographers conducted a survey of trace elements in the Arctic Ocean, traversing the TPD. Near the North Pole, they observed much higher concentrations of trace elements in surface waters than in regions on either side of the current. These trace elements originated from land, and their journey across the Arctic Ocean is made possible by chemical reactions with dissolved organic matter that originates mainly in Arctic rivers. This study reveals the importance of rivers and shelf processes combined with strong ocean currents in supplying trace elements to the central Arctic Ocean and onward to the Atlantic. These trace element inputs are expected to increase as a result of permafrost thawing and increased river runoff in the Arctic, which is warming at a rate much faster than anywhere else on Earth. Since many of the trace elements are essential building blocks for ocean life, these processes could lead to significant changes in the marine ecosystems and fisheries of the Arctic Ocean.
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| 16. |
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| 17. |
- Angelopoulus, M., et al.
(författare)
-
Physical properties of sea ice cores from site MCS_FYI measured on legs 1 to 3 of the MOSAiC expedition.
- 2022
-
Ingår i: PANGAEA.
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We present sea ice temperature and salinity data from first-year ice (FYI) and second-year ice (SYI) relevant to the temporal development of sea ice permeability and brine drainage efficiency from the early growth phase in October 2019 to the onset of spring warming in May 2020. Our dataset was collected in the central Arctic Ocean during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) Expedition in 2019 to 2020. MOSAiC was an international transpolar drift expedition in which the German icebreaker RV Polarstern anchored into an ice floe to gain new insights into Arctic climate over a full annual cycle. In October 2019, RV Polarstern moored to an ice floe in the Siberian sector of the Arctic at 85 degrees north and 137 degrees east to begin the drift towards the North Pole and the Fram Strait via the Transpolar Drift Stream. The data presented here were collected during the first three legs of the expedition, so all the coring activities took place on the same floe. The end dates of legs 1, 2, and 3 were 13 December, 24 February, and 4 June, respectively. The dataset contributed to a baseline study entitled, Deciphering the properties of different Arctic ice types during the growth phase of the MOSAiC floes: Implications for future studies. The study highlights downward directed gas pathways in FYI and SYI by inferring sea ice permeability and potential brine release from several time series of temperature and salinity measurements. The physical properties presented in this paper lay the foundation for subsequent analyses on actual gas contents measured in the ice cores, as well as air-ice and ice-ocean gas fluxes. Sea ice cores were collected with a Kovacs Mark II 9 cm diameter corer. To measure ice temperatures, about 4.5 cm deep holes were drilled into the core (intervals varied by site and leg) . The temperatures were measured by a digital thermometer within minutes after the cores were retrieved. The ice cores were placed into pre-labelled plastic sleeves sealed at the bottom end. The ice cores were transported to RV Polarstern and stored in a -20 degrees Celsius freezer. Each of the cores was sub-sampled, melted at room temperature, and processed for salinity within one or two days. The practical salinity was estimated by measuring the electrical conductivity and temperature of the melted samples using a WTW Cond 3151 salinometer equipped with a Tetra-Con 325 four-electrode conductivity cell. The practical salinity represents the the salinity estimated from the electrical conductivity of the solution. The dataset also contains derived variables, including sea ice density, brine volume fraction, and the Rayleigh number.
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| 18. |
- Angelopoulus, M., et al.
(författare)
-
Physical properties of sea ice cores from site MCS-SYI measured on legs 1 to 3 of the MOSAiC expedition
- 2022
-
Ingår i: PANGAEA.
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We present sea ice temperature and salinity data from first-year ice (FYI) and second-year ice (SYI) relevant to the temporal development of sea ice permeability and brine drainage efficiency from the early growth phase in October 2019 to the onset of spring warming in May 2020. Our dataset was collected in the central Arctic Ocean during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) Expedition in 2019 to 2020. MOSAiC was an international transpolar drift expedition in which the German icebreaker RV Polarstern anchored into an ice floe to gain new insights into Arctic climate over a full annual cycle. In October 2019, RV Polarstern moored to an ice floe in the Siberian sector of the Arctic at 85 degrees north and 137 degrees east to begin the drift towards the North Pole and the Fram Strait via the Transpolar Drift Stream. The data presented here were collected during the first three legs of the expedition, so all the coring activities took place on the same floe. The end dates of legs 1, 2, and 3 were 13 December, 24 February, and 4 June, respectively. The dataset contributed to a baseline study entitled, Deciphering the properties of different Arctic ice types during the growth phase of the MOSAiC floes: Implications for future studies. The study highlights downward directed gas pathways in FYI and SYI by inferring sea ice permeability and potential brine release from several time series of temperature and salinity measurements. The physical properties presented in this paper lay the foundation for subsequent analyses on actual gas contents measured in the ice cores, as well as air-ice and ice-ocean gas fluxes. Sea ice cores were collected with a Kovacs Mark II 9 cm diameter corer. To measure ice temperatures, about 4.5 cm deep holes were drilled into the core (intervals varied by site and leg) . The temperatures were measured by a digital thermometer within minutes after the cores were retrieved. The ice cores were placed into pre-labelled plastic sleeves sealed at the bottom end. The ice cores were transported to RV Polarstern and stored in a -20 degrees Celsius freezer. Each of the cores was sub-sampled, melted at room temperature, and processed for salinity within one or two days. The practical salinity was estimated by measuring the electrical conductivity and temperature of the melted samples using a WTW Cond 3151 salinometer equipped with a Tetra-Con 325 four-electrode conductivity cell. The practical salinity represents the the salinity estimated from the electrical conductivity of the solution. The dataset also contains derived variables, including sea ice density, brine volume fraction, and the Rayleigh number.
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| 19. |
- Fukui, A., et al.
(författare)
-
TOI-1749: an M dwarf with a Trio of Planets including a Near-resonant Pair
- 2021
-
Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 162:4
-
Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of one super-Earth- (TOI-1749b) and two sub-Neptune-sized planets (TOI-1749c and TOI-1749d) transiting an early M dwarf at a distance of 100 pc, which were first identified as planetary candidates using data from the TESS photometric survey. We have followed up this system from the ground by means of multiband transit photometry, adaptive optics imaging, and low-resolution spectroscopy, from which we have validated the planetary nature of the candidates. We find that TOI-1749b, c, and d have orbital periods of 2.39, 4.49, and 9.05 days, and radii of 1.4, 2.1, and 2.5 R (circle plus), respectively. We also place 95% confidence upper limits on the masses of 57, 14, and 15 M (circle plus) for TOI-1749b, c, and d, respectively, from transit timing variations. The periods, sizes, and tentative masses of these planets are in line with a scenario in which all three planets initially had a hydrogen envelope on top of a rocky core, and only the envelope of the innermost planet has been stripped away by photoevaporation and/or core-powered mass-loss mechanisms. These planets are similar to other planetary trios found around M dwarfs, such as TOI-175b,c,d and TOI-270b,c,d, in the sense that the outer pair has a period ratio within 1% of 2. Such a characteristic orbital configuration, in which an additional planet is located interior to a near 2:1 period-ratio pair, is relatively rare around FGK dwarfs.
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| 20. |
- Charette, M, et al.
(författare)
-
The Transpolar Drift as a Source of Riverine and Shelf‐Derived Trace Elements to the Central Arctic Ocean
- 2020
-
Ingår i: Journal of Geophysical Research - Oceans. - 2169-9275 .- 2169-9291. ; 125, s. 1-34
-
Tidskriftsartikel (refereegranskat)abstract
- A major surface circulation feature of the Arctic Ocean is the Transpolar Drift (TPD), a current that transports river‐influenced shelf water from the Laptev and East Siberian Seas toward the center of the basin and Fram Strait. In 2015, the international GEOTRACES program included a high‐resolution pan‐Arctic survey of carbon, nutrients, and a suite of trace elements and isotopes (TEIs). The cruises bisected the TPD at two locations in the central basin, which were defined by maxima in meteoric water and dissolved organic carbon concentrations that spanned 600 km horizontally and ~25–50 m vertically. Dissolved TEIs such as Fe, Co, Ni, Cu, Hg, Nd, and Th, which are generally particle‐reactive but can be complexed by organic matter, were observed at concentrations much higher than expected for the openocean setting. Other trace element concentrations such as Al, V, Ga, and Pb were lower than expected due to scavenging over the productive East Siberian and Laptev shelf seas. Using a combination of radionuclide tracers and ice drift modeling, the transport rate for the core of the TPD was estimated at 0.9 ± 0.4 Sv(106m3 s−1). This rate was used to derive the mass flux for TEIs that were enriched in the TPD, revealing the importance of lateral transport in supplying materials beneath the ice to the central Arctic Ocean and potentially to the North Atlantic Ocean via Fram Strait. Continued intensification of the Arctic hydrologicc ycle and permafrost degradation will likely lead to an increase in the flux of TEIs into the Arctic Ocean.
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| 21. |
- Feng, Shaohong, et al.
(författare)
-
Dense sampling of bird diversity increases power of comparative genomics
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833
-
Tidskriftsartikel (refereegranskat)abstract
- Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
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| 22. |
- Morris, A. M., et al.
(författare)
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Evidence for low‐pressure crustal anatexis during the northeast atlantic break‐up
- 2024
-
Ingår i: Geochemistry Geophysics Geosystems. - : American Geophysical Union (AGU). - 1525-2027. ; 25:7
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Tidskriftsartikel (refereegranskat)abstract
- While basaltic volcanism is dominant during rifting and continental breakup, felsic magmatism may be a significant component of some rift margins. During International Ocean Discovery Program (IODP) Expedition 396 on the continental margin of Norway, a graphite-garnet-cordierite bearing dacitic unit (the Mimir dacite) was recovered in two holes within early Eocene sediments on Mimir High (Site U1570), a marginal high on the Vøring Transform Margin. Here, we present a comprehensive textural, petrological, and geochemical study of the Mimir dacite in order to assess its origin and discuss the geodynamic implications. The major mineral phases (garnet, cordierite, quartz, plagioclase, alkali feldspar) are hosted in a fresh rhyolitic, vesicular, glassy matrix that is locally mingled with sediments. The major element chemistry of garnet and cordierite, the presence of zircon inclusions with inherited cores, and thermobarometric calculations all support an upper crustal metapelitic origin. While most magma-rich margin models favor crustal anatexis in the lower crust, thermobarometric calculations performed here show that the Mimir dacite was produced at upper-crustal depths (<5 kbar, 18 km depth) and high temperature (750–800°C) with up to 3 wt% water content. In situ U-Pb analyses on zircon inclusions give a magmatic crystallization age of 54.6 ± 1.1 Ma, consistent with emplacement that post-dates the Paleocene-Eocene Thermal Maximum. Our results suggest that the opening of the Northeast Atlantic was associated with a phase of low-pressure, high-temperature crustal anatexis preceding the main phase of magmatism.
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| 23. |
- Holdsworth, D. L., et al.
(författare)
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TESS cycle 1 observations of roAp stars with 2-min cadence data
- 2021
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 506:1, s. 1073-1110
-
Tidskriftsartikel (refereegranskat)abstract
- We present the results of a systematic search for new rapidly oscillating Ap (roAp) stars using the 2-min cadence data collected by the Transiting Exoplanet Survey Satellite (TESS) during its Cycle 1 observations. We identify 12 new roAp stars. Amongst these stars we discover the roAp star with the longest pulsation period, another with the shortest rotation period, and six with multiperiodic variability. In addition to these new roAp stars, we present an analysis of 44 known roAp stars observed by TESS during Cycle 1, providing the first high-precision and homogeneous sample of a significant fraction of the known roAp stars. The TESS observations have shown that almost 60 percent (33) of our sample of stars are multiperiodic, providing excellent cases to test models of roAp pulsations, and from which the most rewarding asteroseismic results can be gleaned. We report four cases of the occurrence of rotationally split frequency multiplets that imply different mode geometries for the same degree modes in the same star. This provides a conundrum in applying the oblique pulsator model to the roAp stars. Finally, we report the discovery of non-linear mode interactions in alpha Cir (TIC402546736, HD128898) around the harmonic of the principal mode - this is only the second case of such a phenomenon.
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| 24. |
- Holdsworth, D. L., et al.
(författare)
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TESS Cycle 2 observations of roAp stars with 2-min cadence data
- 2024
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 527:4, s. 9548-9580
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of a systematic search of the Transiting Exoplanet Survey Satellite (TESS) 2-min cadence data for new rapidly oscillating Ap (roAp) stars observed during the Cycle 2 phase of its mission. We find seven new roAp stars previously unreported as such and present the analysis of a further 25 roAp stars that are already known. Three of the new stars show multiperiodic pulsations, while all new members are rotationally variable stars, leading to almost 70 per cent (22) of the roAp stars presented being α2 CVn-type variable stars. We show that targeted observations of known chemically peculiar stars are likely to overlook many new roAp stars, and demonstrate that multiepoch observations are necessary to see pulsational behaviour changes. We find a lack of roAp stars close to the blue edge of the theoretical roAp instability strip, and reaffirm that mode instability is observed more frequently with precise, space-based observations. In addition to the Cycle 2 observations, we analyse TESS data for all-known roAp stars. This amounts to 18 further roAp stars observed by TESS. Finally, we list six known roAp stars that TESS is yet to observe. We deduce that the incidence of roAp stars amongst the Ap star population is just 5.5 per cent, raising fundamental questions about the conditions required to excite pulsations in Ap stars. This work, coupled with our previous work on roAp stars in Cycle 1 observations, presents the most comprehensive, homogeneous study of the roAp stars in the TESS nominal mission, with a collection of 112 confirmed roAp stars in total.
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| 25. |
- Angelopoulos, M., et al.
(författare)
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Physical properties of sea ice cores from site BGC2 measured on legs 1 to 3 of the MOSAiC expedition
- 2022
-
Ingår i: PANGAEA.
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We present sea ice temperature and salinity data from first-year ice (FYI) and second-year ice (SYI) relevant to the temporal development of sea ice permeability and brine drainage efficiency from the early growth phase in October 2019 to the onset of spring warming in May 2020. Our dataset was collected in the central Arctic Ocean during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) Expedition in 2019 to 2020. MOSAiC was an international transpolar drift expedition in which the German icebreaker RV Polarstern anchored into an ice floe to gain new insights into Arctic climate over a full annual cycle. In October 2019, RV Polarstern moored to an ice floe in the Siberian sector of the Arctic at 85 degrees north and 137 degrees east to begin the drift towards the North Pole and the Fram Strait via the Transpolar Drift Stream. The data presented here were collected during the first three legs of the expedition, so all the coring activities took place on the same floe. The end dates of legs 1, 2, and 3 were 13 December, 24 February, and 4 June, respectively. The dataset contributed to a baseline study entitled, Deciphering the properties of different Arctic ice types during the growth phase of the MOSAiC floes: Implications for future studies. The study highlights downward directed gas pathways in FYI and SYI by inferring sea ice permeability and potential brine release from several time series of temperature and salinity measurements. The physical properties presented in this paper lay the foundation for subsequent analyses on actual gas contents measured in the ice cores, as well as air-ice and ice-ocean gas fluxes. Sea ice cores were collected with a Kovacs Mark II 9 cm diameter corer. To measure ice temperatures, about 4.5 cm deep holes were drilled into the core (intervals varied by site and leg) . The temperatures were measured by a digital thermometer within minutes after the cores were retrieved. The ice cores were placed into pre-labelled plastic sleeves sealed at the bottom end. The ice cores were transported to RV Polarstern and stored in a -20 degrees Celsius freezer. Each of the cores was sub-sampled, melted at room temperature, and processed for salinity within one or two days. The practical salinity was estimated by measuring the electrical conductivity and temperature of the melted samples using a WTW Cond 3151 salinometer equipped with a Tetra-Con 325 four-electrode conductivity cell. The practical salinity represents the the salinity estimated from the electrical conductivity of the solution. The dataset also contains derived variables, including sea ice density, brine volume fraction, and the Rayleigh number.
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| 26. |
- Bogie, JFJ, et al.
(författare)
-
Stearoyl-CoA desaturase-1 impairs the reparative properties of macrophages and microglia in the brain
- 2020
-
Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 217:5
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Tidskriftsartikel (refereegranskat)abstract
- Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Macrophages and microglia are crucially involved in the formation and repair of demyelinated lesions. Here we show that myelin uptake temporarily skewed these phagocytes toward a disease-resolving phenotype, while sustained intracellular accumulation of myelin induced a lesion-promoting phenotype. This phenotypic shift was controlled by stearoyl-CoA desaturase-1 (SCD1), an enzyme responsible for the desaturation of saturated fatty acids. Monounsaturated fatty acids generated by SCD1 reduced the surface abundance of the cholesterol efflux transporter ABCA1, which in turn promoted lipid accumulation and induced an inflammatory phagocyte phenotype. Pharmacological inhibition or phagocyte-specific deficiency of Scd1 accelerated remyelination ex vivo and in vivo. These findings identify SCD1 as a novel therapeutic target to promote remyelination.
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| 27. |
- Bowman, E. M. L., et al.
(författare)
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Advancing specificity in delirium: The delirium subtyping initiative
- 2024
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Ingår i: Alzheimers & Dementia. - 1552-5260. ; 20:1, s. 183-194
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDDelirium, a common syndrome with heterogeneous etiologies and clinical presentations, is associated with poor long-term outcomes. Recording and analyzing all delirium equally could be hindering the field's understanding of pathophysiology and identification of targeted treatments. Current delirium subtyping methods reflect clinically evident features but likely do not account for underlying biology. METHODSThe Delirium Subtyping Initiative (DSI) held three sessions with an international panel of 25 experts. RESULTSMeeting participants suggest further characterization of delirium features to complement the existing Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision diagnostic criteria. These should span the range of delirium-spectrum syndromes and be measured consistently across studies. Clinical features should be recorded in conjunction with biospecimen collection, where feasible, in a standardized way, to determine temporal associations of biology coincident with clinical fluctuations. DISCUSSIONThe DSI made recommendations spanning the breadth of delirium research including clinical features, study planning, data collection, and data analysis for characterization of candidate delirium subtypes. HighlightsDelirium features must be clearly defined, standardized, and operationalized.Large datasets incorporating both clinical and biomarker variables should be analyzed together.Delirium screening should incorporate communication and reasoning.
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| 28. |
- Das, J., et al.
(författare)
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Autologous haematopoietic stem cell transplantation as a first-line disease-modifying therapy in patients with 'aggressive' multiple sclerosis
- 2021
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Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 27:8, s. 1198-1204
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Tidskriftsartikel (refereegranskat)abstract
- Background:Autologous haematopoietic stem cell transplantation (AHSCT) is an effective treatment for patients with multiple sclerosis (MS) who have highly active disease, despite the use of standard disease-modifying therapies (DMTs). However, the optimal time for offering AHSCT to patients with ‘aggressive’ MS is yet to be established.Objectives:The objective was to explore the safety and efficacy of AHSCT as a first-line DMT in patients with ‘aggressive’ MS.Methods:All patients with ‘aggressive’ MS who received AHSCT as a first-line DMT in five European and North American centres were retrospectively evaluated.Results:Twenty patients were identified. The median interval between diagnosis and AHSCT was 5 (1–20) months. All had multiple poor prognostic markers with a median pre-transplant Expanded Disability Status Scale (EDSS) score of 5.0 (1.5–9.5). After a median follow-up of 30 (12–118) months, the median EDSS score improved to 2.0 (0–6.5, p < 0.0001). No patient had further relapses. Three had residual magnetic resonance imaging (MRI) disease activities in the first 6 months post-transplant, but no further new or enhancing lesions were observed in subsequent scans.Conclusion:AHSCT is safe and effective as a first-line DMT in inducing rapid and sustained remission in patients with ‘aggressive’ MS.
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| 29. |
- Fabian, ID, et al.
(författare)
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Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries
- 2021
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Ingår i: The British journal of ophthalmology. - : BMJ. - 1468-2079 .- 0007-1161. ; 105:10, s. 1435-1443
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Tidskriftsartikel (refereegranskat)abstract
- The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe.MethodsA cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries.ResultsCapture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI −12.4 to −5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease.ConclusionsFewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral.
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| 30. |
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| 31. |
- Naidu, R., et al.
(författare)
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Per- and poly-fluoroalkyl substances (PFAS) : Current status and research needs
- 2020
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Ingår i: Environmental Technology & Innovation. - : Elsevier BV. - 2352-1864. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- An expert workshop focusing on per- and poly-fluoroalkyl substances (PFAS) was held in Adelaide, South Australia, Australia in September 2019 following the 8th International Contaminated Site Remediation Conference — CleanUp 2019. The workshop was organised by the Cooperative Research Centre for Contamination and Remediation of the Environment (CRC CARE) and was chaired by Professor Ravi Naidu, CEO and Managing Director of CRC CARE and Director of the Global Centre for Environmental Remediation at the University of Newcastle, NSW. The purpose of the workshop, which was attended by more than 50 experts in the field of contaminated land assessment and management, was to discuss the current state of play and research needs relating to PFAS contaminated sites. This paper provides a summary of the discussions and conclusions and lists actions and needs that the expert group identified as critical for pursuing successful PFAS management and remedy approaches.This paper is intended to capture the shared information, comments, and current thinking related to PFAS challenges and research needs as identified by the group of expert participants; the write up is not intended to be a complete dissertation on the science and work that has been carried out. With a fast-evolving subject and increased government and public attention on PFAS presence in the environment, the group was convened with the objective of providing value in contributing to solutions to the PFAS challenges that are faced both in Australia and internationally. The text contained herein provides references to observations and methods that the experts drew on in their discussions and in support of their commentary; documentation of the original references was not provided, and the reader should consult the scientific literature if further information and confirmation of observations is required. Following a brief on the background to PFAS challenges, the paper focusses on research gaps identified by experts with focus on Australian soils and groundwater including climatic patterns, an overview of PFAS research in Australia with emphasis on:RegulatoryAnalytical considerationsEcological and Human Health RisksFate and TransportRemediation and Risk Management.
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| 32. |
- Chamberlain, E. J., et al.
(författare)
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Impacts of sea ice melting procedures on measurements of microbial community structure
- 2022
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Ingår i: Elementa. - : University of California Press. - 2325-1026. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Microorganisms play critical roles in sea ice biogeochemical processes. However, microbes living within sea ice can be challenging to sample for scientific study. Because most techniques for microbial analysis are optimized for liquid samples, sea ice samples are typically melted first, often applying a buffering method to mitigate osmotic lysis. Here, we tested commonly used melting procedures on three different ice horizons of springtime, first year, land-fast Arctic sea ice to investigate potential methodological impacts on resulting measurements of cell abundance, photophysiology, and microbial community structure as determined by 16S and 18S rRNA gene amplicon sequencing. Specifically, we compared two buffering methods using NaCl solutions (“seawater,” melting the ice in an equal volume of 35-ppt solution, and “isohaline,” melting with a small volume of 250-ppt solution calculated to yield meltwater at estimated in situ brine salinity) to direct ice melting (no buffer addition) on both mechanically “shaved” and “non-shaved” samples. Shaving the ice shortened the melting process, with no significant impacts on the resulting measurements. The seawater buffer was best at minimizing cell lysis for this ice type, retaining the highest number of cells and chlorophyll a concentration. Comparative measurements of bacterial (16S) community structure highlighted ecologically relevant subsets of the community that were significantly more abundant in the buffered samples. The results for eukaryotic (18S) community structure were less conclusive. Taken together, our results suggest that an equivalent-volume seawater-salinity buffered melt is best at minimizing cell loss due to osmotic stress for springtime Arctic sea ice, but that either buffer will reduce bias in community composition when compared to direct melting. Overall, these findings indicate potential methodological biases that should be considered before developing a sea ice melting protocol for microbiological studies and afterwards, when interpreting biogeochemical or ecological meaning of the results.
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| 33. |
- Hirscher, Michael, et al.
(författare)
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Materials for hydrogen-based energy storage - past, recent progress and future outlook
- 2020
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Ingår i: Journal of Alloys and Compounds. - : Elsevier BV. - 0925-8388 .- 1873-4669. ; 827
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Tidskriftsartikel (refereegranskat)abstract
- Globally, the accelerating use of renewable energy sources, enabled by increased efficiencies and reduced costs, and driven by the need to mitigate the effects of climate change, has significantly increased research in the areas of renewable energy production, storage, distribution and end-use. Central to this discussion is the use of hydrogen, as a clean, efficient energy vector for energy storage. This review, by experts of Task 32, Hydrogen-based Energy Storage of the International Energy Agency, Hydrogen TCP, reports on the development over the last 6 years of hydrogen storage materials, methods and techniques, including electrochemical and thermal storage systems. An overview is given on the background to the various methods, the current state of development and the future prospects. The following areas are covered; porous materials, liquid hydrogen carriers, complex hydrides, intermetallic hydrides, electrochemical storage of energy, thermal energy storage, hydrogen energy systems and an outlook is presented for future prospects and research on hydrogen-based energy storage.
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| 34. |
- Hjelmstedt, P., et al.
(författare)
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Effects of prophylactic antibiotic-treatment on post-surgical recovery following intraperitoneal bio-logger implantation in rainbow trout
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Bio-logging devices can provide unique insights on the life of freely moving animals. However, implanting these devices often requires invasive surgery that causes stress and physiological side-effects. While certain medications in connection to surgeries have therapeutic capacity, others may have aversive effects. Here, we hypothesized that the commonly prescribed prophylactic treatment with enrofloxacin would increase the physiological recovery rate and reduce the presence of systemic inflammation following the intraperitoneal implantation of a heart rate bio-logger in rainbow trout (Oncorhynchus mykiss). To assess post-surgical recovery, heart rate was recorded for 21 days in trout with or without enrofloxacin treatment. Contrary to our hypothesis, treated trout exhibited a prolonged recovery time and elevated resting heart rates during the first week of post-surgical recovery compared to untreated trout. In addition, an upregulated mRNA expression of TNFα in treated trout indicate a possible inflammatory response 21 days post-surgery. Interestingly, the experience level of the surgeon was observed to have a long-lasting impact on heart rate. In conclusion, our study showed no favorable effects of enrofloxacin treatment. Our findings highlight the importance of adequate post-surgical recovery times and surgical training with regards to improving the welfare of experimental animals and reliability of research outcomes. © 2020, The Author(s).
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| 35. |
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| 36. |
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| 37. |
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| 38. |
- Mock, Thomas, et al.
(författare)
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Multiomics in the central Arctic Ocean for benchmarking biodiversity change
- 2022
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 20:10
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Tidskriftsartikel (refereegranskat)abstract
- Multiomics approaches need to be applied in the central Arctic Ocean to benchmark biodiversity change and to identify novel species and their genes. As part of MOSAiC, EcoOmics will therefore be essential for conservation and sustainable bioprospecting in one of the least explored ecosystems on Earth.
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| 39. |
- Saarelma, S., et al.
(författare)
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Density pedestal prediction model for tokamak plasmas
- 2024
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 64:7
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Tidskriftsartikel (refereegranskat)abstract
- A model for the pedestal density prediction based on neutral penetration combined with pedestal transport is presented. The model is tested against a pedestal database of JET-ILW Type I ELMy H-modes showing good agreement over a wide range of parameters both in standalone modelling (using the experimental temperature profile) and in full Europed modelling that predicts both density and temperature pedestals simultaneously. The model is further tested for ASDEX Upgrade and MAST-U Type I ELMy H-modes and both are found to agree with the same model parameters as for JET-ILW. The JET-ILW experiment where the isotope of the main ion is varied in a D/T scan at constant gas rate and constant βN is successfully modelled as long as the separatrix density (ne,sep) and pedestal transport coefficient ratio (D/χ) are varied in accordance with the experimentally observed variation of ne,sep and the isotope dependence of D/χ found in gyrokinetic simulations. The predictions are found to be sensitive to ne,sep which is why the model is combined with an ne,sep model to predict the pedestal for the STEP fusion reactor.
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| 40. |
- Smith, Madison M., et al.
(författare)
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Thin and transient meltwater layers and false bottoms in the Arctic sea ice pack—Recent insights on these historically overlooked features
- 2023
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Ingår i: Elementa: Science of the Anthropocene. - 2325-1026. ; 11:1
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Forskningsöversikt (refereegranskat)abstract
- The rapid melt of snow and sea ice during the Arctic summer provides a significant source of low-salinity meltwater to the surface ocean on the local scale. The accumulation of this meltwater on, under, and around sea ice floes can result in relatively thin meltwater layers in the upper ocean. Due to the small-scale nature of these upper-ocean features, typically on the order of 1 m thick or less, they are rarely detected by standard methods, but are nevertheless pervasive and critically important in Arctic summer. Observations during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition in summer 2020 focused on the evolution of such layers and made significant advancements in understanding their role in the coupled Arctic system. Here we provide a review of thin meltwater layers in the Arctic, with emphasis on the new findings from MOSAiC. Both prior and recent observational datasets indicate an intermittent yet longlasting (weeks to months) meltwater layer in the upper ocean on the order of 0.1 m to 1.0 m in thickness, with a large spatial range. The presence of meltwater layers impacts the physical system by reducing bottom ice melt and allowing new ice formation via false bottom growth. Collectively, the meltwater layer and false bottoms reduce atmosphere-ocean exchanges of momentum, energy, and material.The impacts on the coupled Arctic system are far-reaching, including acting as a barrier for nutrient and gas exchange and impacting ecosystem diversity and productivity.
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| 41. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 42. |
- Berry, Joe Scott, et al.
(författare)
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Examining the biological pathways underlying clinical heterogeneity in Sjogren's syndrome : proteomic and network analysis
- 2024
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 83:1, s. 88-95
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Stratification approaches are vital to address clinical heterogeneity in Sjogren's syndrome (SS). We previously described that the Newcastle Sjogren's Stratification Tool (NSST) identified four distinct clinical subtypes of SS. We performed proteomic and network analysis to analyse the underlying pathobiology and highlight potential therapeutic targets for different SS subtypes.Method: We profiled serum proteins using O-link technology of 180 SS subjects. We used 5 O-link proteomics panels which included a total of 454 unique proteins. Network reconstruction was performed using the ARACNE algorithm, with differential expression estimates overlaid on these networks to reveal the key subnetworks of differential expression. Furthermore, data from a phase III trial of tocilizumab in SS were reanalysed by stratifying patients at baseline using NSST.Results: Our analysis highlights differential expression of chemokines, cytokines and the major autoantigen TRIM21 between the SS subtypes. Furthermore, we observe differential expression of several transcription factors associated with energy metabolism and redox balance namely APE1/Ref-1, FOXO1, TIGAR and BACH1. The differentially expressed proteins were inter-related in our network analysis, supporting the concept that distinct molecular networks underlie the clinical subtypes of SS. Stratification of patients at baseline using NSST revealed improvement of fatigue score only in the subtype expressing the highest levels of serum IL-6.Conclusions: Our data provide clues to the pathways contributing to the glandular and non-glandular manifestations of SS and to potential therapeutic targets for different SS subtypes. In addition, our analysis highlights the need for further exploration of altered metabolism and mitochondrial dysfunction in the context of SS subtypes.
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| 43. |
- Bowman, E. M. L., et al.
(författare)
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Factors influencing resilience to postoperative delirium in adults undergoing elective orthopaedic surgery
- 2022
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 109:10, s. 908-911
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Tidskriftsartikel (refereegranskat)abstract
- Delirium occurs after elective arthroplasty in 17 per cent of adults1, and is associated with poor outcomes, including cognitive decline2, dementia3,4, and death5. Predisposing and precipitating risk factors accumulate and interact to precipitate delirium6. Much of the current literature analyses delirium as a dichotomous outcome, inevitably placing many people with symptoms of delirium, but falling short of a diagnosis, into the no-delirium group. Freedom from delirium symptoms should be investigated as an outcome. As evidence accumulates that delirium symptoms can also be associated with negative outcomes, it is important to identify the resilient groups in these studies and establish modifiable resilience predictors. Studies have explored risk factors for postoperative delirium; however, none to date has defined or considered delirium resilience as an outcome or phenotype. Resilience may be broadly defined as ‘the ability to withstand or recover quickly from difficult conditions’7,8. The aim of this study was to identify predictors of delirium resilience in the perioperative setting.
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| 44. |
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| 45. |
- Bowman, Louise, et al.
(författare)
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Understanding the use of observational and randomized data in cardiovascular medicine
- 2020
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Ingår i: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645. ; 41:27, s. 2571-2578
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Tidskriftsartikel (refereegranskat)abstract
- The availability of large datasets from multiple sources [e.g. registries, biobanks, electronic health records (EHRs), claims or billing databases, implantable devices, wearable sensors, and mobile apps], coupled with advances in computing and analytic technologies, have provided new opportunities for conducting innovative health research. Equally, improved digital access to health information has facilitated the conduct of efficient randomized controlled trials (RCTs) upon which clinical management decisions can be based, for instance, by permitting the identification of eligible patients for recruitment and/or linkage for follow-up via their EHRs. Given these advances in cardiovascular data science and the complexities they behold, it is important that health professionals have clarity on the appropriate use and interpretation of observational, so-called 'real-world', and randomized data in cardiovascular medicine. The Cardiovascular Roundtable of the European Society of Cardiology (ESC) held a workshop to explore the future of RCTs and the current and emerging opportunities for gathering and exploiting complex observational datasets in cardiovascular research. The aim of this article is to provide a perspective on the appropriate use of randomized and observational data and to outline the ESC plans for supporting the collection and availability of clinical data to monitor and improve the quality of care of patients with cardiovascular disease in Europe and provide an infrastructure for undertaking pragmatic RCTs. Moreover, the ESC continues to campaign for greater engagement amongst regulators, industry, patients, and health professionals in the development and application of a more efficient regulatory framework that is able to take maximal advantage of new opportunities for improving the design and efficiency of observational studies and RCT in patients with cardiovascular disease.
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| 46. |
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| 47. |
- Khatri, B, et al.
(författare)
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GENOME-WIDE ASSOCIATION STUDY OF SJOGREN'S SYNDROME IDENTIFIES TEN NEW RISK LOCI
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 30-31
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Sjögren’s syndrome (SS) is a complex autoimmune disease with exocrine gland dysfunction leading to substantial morbidity. There are 10 published genetic susceptibility loci.Objectives:Our genome-wide association study (GWAS) aimed to identify additional risk loci of genome-wide significance (GWS; p<5E-08) in European-derived primary SS.Methods:A total of 3232 cases and 17481 controls genotyped on GWAS arrays and 619 cases and 6171 controls genotyped on ImmunoChip (IC) arrays were imputed after quality control. Logistic regression was calculated adjusting for ancestry using the first 4 principal components to identify SS-associated SNPs. GWAS and IC results were meta-analyzed using weighted Z-scores. Bayesian statistics were used to assign posterior probabilities and define credible SNP sets for each locus. Bioinformatic analyses were used to predict functionality.Results:Seven novel loci exceeded GWS in the GWAS analysis:NAB1,MIR146A-PTTG1,XKR6,MAPT-CRHR1,RPTOR-CHMP6-BAIAP2,TYK2andSYNGR1. Meta-analysis with IC data identified three more novel loci exceeding GWS:CD247,PRDM1-ATG5andTNFAIP3. Several additional loci with suggestive association (p<1E-05) were also identified:ADAMTSL2,CGNL1andPHRF1.Several identified loci have reported functional implications in immune regulation and autoimmune disease. In lupus, rs2431697 correlated with rs2431098, which was shown to alterMIR146Aexpression, resulting in type I interferon pathway imbalance. Similarly,TYK2risk association reportedly drives interferon, IL10 and RET signaling pathways.PRDM1encodes Blimp-1, a master regulator of immune cell differentiation.CD247encodes the zeta subunit of the T cell receptor complex.XKR6is implicated in apoptotic cell ingestion.ATG5is also involved in apoptosis, as well as autophagy and antigen presentation.Additional bioinformatics analyses (Haploreg, Regulome DB, ENCODE, etc.) revealed immune-relevant functional implications for each risk locus. The SS-associated credible set included variants downstream ofTNFAIP3in a region reported to abolish looping between an enhancer and theTNFAIP3promoter in lupus and a coding variant that has been shown to alter NF-kB activity and neutrophil extra-cellular traps. The rs2293765 in the 5’ UTR ofNAB1showed evidence of enhancer/promoter activities. The rs2069235 in theSYNGR1locus showed enhancer and transcription start site activities in B and T cells. The rs7210219 in theMAPT-CRHR1locus showed enhancer/promotor activities in various tissues.Conclusion:We have identified ten novel genetic susceptibility loci associated with SS pathology. Our finding increases the current number of GWS regions in SS patients of European origin, from 10 to 20. Future work is needed to identify and characterize the functional variants in each region.Disclosure of Interests:Bhuwan Khatri: None declared, Tove Ragna Reksten: None declared, Kandice L Tessneer: None declared, Astrid Rasmussen Speakers bureau: Novartis, ThermoFischer, R Hal Scofield Grant/research support from: Pfizer, Simon J. Bowman Consultant of: Astrazeneca, Biogen, BMS, Celgene, Medimmune, MTPharma, Novartis, Ono, UCB, xtlbio, Glapagos, Speakers bureau: Novartis, Joel Guthridge Grant/research support from: Xencor, Bristol Myers Squibb, DXterity, Judith A. James Grant/research support from: Progentec Diagnostics, Inc, Consultant of: Abbvie, Novartis, Jannsen, Lars Ronnblom Grant/research support from: AZ, Speakers bureau: AZ, Blake M Warner: None declared, Xavier Mariette: None declared, Roald Omdal: None declared, Javier Martin Ibanez: None declared, Maria Teruel: None declared, Janicke Liaaen Jensen: None declared, Lara A Aqrawi: None declared, Øyvind Palm: None declared, Marie Wahren-Herlenius: None declared, Torsten Witte: None declared, Roland Jonsson: None declared, Maureen Rischmueller: None declared, A Darise Farris Speakers bureau: Biogen, Marta Alarcon-Riquelme: None declared, Wan-fai Ng: None declared, Kathy L Sivils: None declared, Gunnel Nordmark: None declared, Christopher Lessard: None declared
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| 48. |
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| 49. |
- Ouyang, Wei, et al.
(författare)
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An Open-Source Modular Framework for Automated Pipetting and Imaging Applications
- 2022
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Ingår i: Advanced Biology. - : Wiley. - 2701-0198. ; 6:4, s. 2101063-
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Tidskriftsartikel (refereegranskat)abstract
- The number of samples in biological experiments is continuously increasing, but complex protocols and human error in many cases lead to suboptimal data quality and hence difficulties in reproducing scientific findings. Laboratory automation can alleviate many of these problems by precisely reproducing machine-readable protocols. These instruments generally require high up-front investments, and due to the lack of open application programming interfaces (APIs), they are notoriously difficult for scientists to customize and control outside of the vendor-supplied software. Here, automated, high-throughput experiments are demonstrated for interdisciplinary research in life science that can be replicated on a modest budget, using open tools to ensure reproducibility by combining the tools OpenFlexure, Opentrons, ImJoy, and UC2. This automated sample preparation and imaging pipeline can easily be replicated and established in many laboratories as well as in educational contexts through easy-to-understand algorithms and easy-to-build microscopes. Additionally, the creation of feedback loops, with later pipetting or imaging steps depending on the analysis of previously acquired images, enables the realization of fully autonomous “smart” microscopy experiments. All documents and source files are publicly available to prove the concept of smart lab automation using inexpensive, open tools. It is believed this democratizes access to the power and repeatability of automated experiments.
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| 50. |
- Retamozo, Soledad, et al.
(författare)
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Therapeutic Recommendations for the Management of Older Adult Patients with Sjögren’s Syndrome
- 2021
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Ingår i: Drugs & Aging. - : Springer Science and Business Media LLC. - 1170-229X .- 1179-1969. ; 38:4, s. 265-284
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Tidskriftsartikel (refereegranskat)abstract
- Primary Sjögren’s syndrome (SjS) is a systemic autoimmune disease most commonly diagnosed in middle-aged women. Although the disease can occur at all ages, it is diagnosed between 30 and 60 years of age in two-thirds of patients. In more than 20% of cases, the people are older than 65 years. In this review, we focus on the therapeutic management of primary SjS in older patients, following the recently published 2020 European League Against Rheumatism (EULAR) recommendations for the management of the disease with topical and systemic therapies. These recommendations are applicable to all patients with primary SjS regardless of age at diagnosis, although the therapeutic management in older patients requires additional considerations. Older patients are more likely to have pulmonary, liver, kidney, or heart-related comorbidities (even cognitive disturbances); caution is required when most drugs are used, including muscarinic agents, systemic corticosteroids and synthetic immunosuppressants. It is also important to monitor the use of eye drops containing steroids due to the increased risk of developing cataracts, a frequent ocular complication in the older population. In contrast, the majority of drugs that can be used topically (pilocarpine rinses, eye drops containing topical non-steroidal anti-inflammatory drugs (NSAIDs) or cyclosporine A, topical dermal formulations of NSAIDs) have shown an acceptable safety profile in older patients, as well as rituximab. A rigorous evaluation of the medical history of older patients is essential when drugs included in the EULAR guidelines are prescribed, with special attention to factors frequently related to ageing, such as polypharmacy, the existence of organ-specific comorbidities, or the enhanced susceptibility to infections.
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