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- Dures, E., et al.
(författare)
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2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases
- 2023
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Ingår i: Annals of the Rheumatic Diseases. - 0003-4967 .- 1468-2060.
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Fatigue is prevalent in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and recognised as one of the most challenging symptoms to manage. The existence of multiple factors associated with driving and maintaining fatigue, and the evidence about what improves fatigue has led to a multifaceted approach to its management. However, there are no recommendations for fatigue management in people with I-RMDs. This lack of guidance is challenging for those living with fatigue and health professionals delivering clinical care. Therefore, our aim was to develop EULAR recommendations for the management of fatigue in people with I-RMDs.Methods A multidisciplinary taskforce comprising 26 members from 14 European countries was convened, and two systematic reviews were conducted. The taskforce developed the recommendations based on the systematic review of evidence supplemented with taskforce members' experience of fatigue in I-RMDs.Results Four overarching principles (OAPs) and four recommendations were developed. OAPs include health professionals' awareness that fatigue encompasses multiple biological, psychological and social factors which should inform clinical care. Fatigue should be monitored and assessed, and people with I-RMDs should be offered management options. Recommendations include offering tailored physical activity and/or tailored psychoeducational interventions and/or, if clinically indicated, immunomodulatory treatment initiation or change. Patient-centred fatigue management should consider the individual's needs and preferences, their clinical disease activity, comorbidities and other psychosocial and contextual factors through shared decision-making.Conclusions These 2023 EULAR recommendations provide consensus and up-to-date guidance on fatigue management in people with I-RMDs.
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- Le Coroller, H., et al.
(författare)
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K-Stacker : an algorithm to hack the orbital parameters of planets hidden in high-contrast imaging
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 639
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Tidskriftsartikel (refereegranskat)abstract
- Context. Recent high-contrast imaging surveys, using the Spectro-Polarimetic High contrast imager for Exoplanets REsearch (SPHERE) or the Gemini Planet Imager in search of planets in young, nearby systems, have shown evidence of a small number ofgiant planets at relatively large separation beyond 10–30 au, where those surveys are the most sensitive. Access to smaller physical separations between 5 and 30 au is the next step for future planet imagers on 10 m telescopes and the next generation of extremely large telescopes in order to bridge the gap with indirect techniques such as radial velocity, transit, and soon astrometry with Gaia. In addition to new technologies and instruments, the development of innovative observing strategies combined with optimized data processing tools is participating in the improvement of detection capabilities at very close angular separation. In that context, we recently proposed a new algorithm, Keplerian-Stacker, which combines multiple observations acquired at different epochs and takes into account the orbital motion of a potential planet present in the images to boost the ultimate detection limit. We showed that this algorithm is able to find planets in time series of simulated images of the SPHERE InfraRed Dual-band Imager and Spectrograph (IRDIS) even when a planet remains undetected at one epoch.Aims. Our goal is to test and validate the K-Stacker algorithm performances on real SPHERE datasets to demonstrate the resilience of this algorithm to instrumental speckles and the gain offered in terms of true detection. This will motivate future dedicated multi-epoch observation campaigns of well-chosen, young, nearby systems and very nearby stars carefully selected to search for planets in emitted and reflected light, respectively, to open a new path concerning the observing strategy used with current and future planet imagers.Methods. To test K-Stacker, we injected fake planets and scanned the low signal-to-noise ratio (S/N) regime in a series of raw observations obtained by the SPHERE/IRDIS instrument in the course of the SPHERE High-contrast ImagiNg survey for Exoplanets. We also considered the cases of two specific targets intensively monitored during this campaign: β Pictoris and HD 95086. For each target and epoch, the data were reduced using standard angular differential imaging processing techniques and then recombined with K-Stackerto recover the fake planetary signals. In addition, the known exoplanets β Pictoris b and HD 95086 b previously identified at lower S/N in single epochs have also been recovered by K-Stacker.Results. We show that K-Stacker achieves a high success rate of ≈100% when the S/N of the planet in the stacked image reaches≈9. The improvement of the S/N is given as the square root of the total exposure time contained in the data being combined. At S/N<6−7, the number of false positives is high near the coronagraphic mask, but a chromatic study or astrophysical criteria can help to disentangle between a bright speckle and a true detection. During the blind test and the redetection of HD 95086 b, and β Pic b, we highlight the ability of K-Stacker to find orbital solutions consistent with those derived by the current Markov chain Monte Carlo orbital fitting techniques. This confirms that in addition to the detection gain, K-Stacker offers the opportunity to characterize the most probable orbital solutions of the exoplanets recovered at low S/N.
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- Wrobel, L., et al.
(författare)
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Compounds activating VCP D1 ATPase enhance both autophagic and proteasomal neurotoxic protein clearance
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Enhancing the removal of aggregate-prone toxic proteins is a rational therapeutic strategy for a number of neurodegenerative diseases, especially Huntington's disease and various spinocerebellar ataxias. Ideally, such approaches should preferentially clear the mutant/misfolded species, while having minimal impact on the stability of wild-type/normally-folded proteins. Furthermore, activation of both ubiquitin-proteasome and autophagy-lysosome routes may be advantageous, as this would allow effective clearance of both monomeric and oligomeric species, the latter which are inaccessible to the proteasome. Here we find that compounds that activate the D1 ATPase activity of VCP/p97 fulfill these requirements. Such effects are seen with small molecule VCP activators like SMER28, which activate autophagosome biogenesis by enhancing interactions of PI3K complex components to increase PI(3)P production, and also accelerate VCP-dependent proteasomal clearance of such substrates. Thus, this mode of VCP activation may be a very attractive target for many neurodegenerative diseases. Several neurodegenerative diseases are characterized by the aggregation of cytoplasmic proteins. Here, the authors demonstrate that the small molecule SMER28 activates VCP, which enhances both autophagic and proteasomal clearance of aggregate-prone proteins.
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- Layton, K. K. S., et al.
(författare)
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Predicting the future of our oceans : Evaluating genomic forecasting approaches in marine species
- 2024
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Ingår i: Global Change Biology. - : John Wiley & Sons. - 1354-1013 .- 1365-2486. ; 30:3
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Forskningsöversikt (refereegranskat)abstract
- Climate change is restructuring biodiversity on multiple scales and there is a pressing need to understand the downstream ecological and genomic consequences of this change. Recent advancements in the field of eco-evolutionary genomics have sought to include evolutionary processes in forecasting species' responses to climate change (e.g., genomic offset), but to date, much of this work has focused on terrestrial species. Coastal and offshore species, and the fisheries they support, may be even more vulnerable to climate change than their terrestrial counterparts, warranting a critical appraisal of these approaches in marine systems. First, we synthesize knowledge about the genomic basis of adaptation in marine species, and then we discuss the few examples where genomic forecasting has been applied in marine systems. Next, we identify the key challenges in validating genomic offset estimates in marine species, and we advocate for the inclusion of historical sampling data and hindcasting in the validation phase. Lastly, we describe a workflow to guide marine managers in incorporating these predictions into the decision-making process. Predicting climate change impacts is of central importance in marine ecosystems that provide a major source of nutrition to global communities and this work must be based on a sound understanding of both ecological and genomic impacts. This opinion synthesizes knowledge about the genomic basis of adaptation in marine species, highlights the few examples where genomic forecasting has been applied in marine systems, identifies the key challenges in validating genomic offset estimates in marine species, and provides a workflow to guide marine managers in incorporating these predictions into the decision-making process.
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