| 11. |
- Turner, D. J., et al.
(författare)
-
The XMM Cluster Survey : an independent demonstration of the fidelity of the eFEDS galaxy cluster data products and implications for future studies
- 2022
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 517:1, s. 657-674
-
Tidskriftsartikel (refereegranskat)abstract
- We present the first comparison between properties of clusters of galaxies detected by the eROSITA Final Equatorial-Depth Survey (eFEDS) and the XMM Cluster Survey (XCS). We have compared, in an ensemble fashion, properties from the eFEDS X-ray cluster catalogue with those from the Ultimate XMM eXtragaLactic (XXL) survey project (XXL-100-GC). We find the redshift and temperature (T-X) distributions to be similar, with a larger proportion of clusters above 4 keV in the XXL-100-GC sample; fractional temperature uncertainties are significantly larger in eFEDS compared to XXL. We find 62 eFEDS cluster candidates with XMM data (eFEDS-XMM sample); 10 do not have good enough XMM data to confirm or deny, 11 are classed as sample contaminants, and 4 have their X-ray flux contaminated by another source. The majority of eFEDS-XMM sources have longer XMM exposures than eFEDS, and most eFEDS positions are within 100 kpc of XCS positions. Our eFEDS-XCS sample of 37 clusters is used to calculate minimum sample contamination fractions of similar to 18 and similar to 9 per cent in the eFEDS X-ray and optically confirmed samples, respectively, in general agreement with eFEDS findings. We directly compare 29 X-ray luminosities (L-X) measured by eFEDS and XCS, finding excellent agreement. Eight clusters have a T-X measured by XCS and eFEDS, and we find that XMM temperatures are 25 +/- 9 per cent larger than their eROSITA counterparts. Finally, we construct L-X-T-X scaling relations based on eFEDS and XCS measurements, which are in tension; the tension is decreased when we measure a third scaling relation with calibrated XCS temperatures.
|
|
| 12. |
- Benatar, Michael, et al.
(författare)
-
Preventing amyotrophic lateral sclerosis : insights from pre-symptomatic neurodegenerative diseases
- 2022
-
Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 145:1, s. 27-44
-
Forskningsöversikt (refereegranskat)abstract
- Significant progress has been made in understanding the pre-symptomatic phase of amyotrophic lateral sclerosis. While much is still unknown, advances in other neurodegenerative diseases offer valuable insights. Indeed, it is increasingly clear that the well-recognized clinical syndromes of Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal muscular atrophy and frontotemporal dementia are also each preceded by a pre-symptomatic or prodromal period of varying duration, during which the underlying disease process unfolds, with associated compensatory changes and loss of inherent system redundancy. Key insights from these diseases highlight opportunities for discovery in amyotrophic lateral sclerosis. The development of biomarkers reflecting amyloid and tau has led to a shift in defining Alzheimer's disease based on inferred underlying histopathology. Parkinson's disease is unique among neurodegenerative diseases in the number and diversity of non-genetic biomarkers of pre-symptomatic disease, most notably REM sleep behaviour disorder. Huntington's disease benefits from an ability to predict the likely timing of clinically manifest disease based on age and CAG-repeat length alongside reliable neuroimaging markers of atrophy. Spinal muscular atrophy clinical trials have highlighted the transformational value of early therapeutic intervention, and studies in frontotemporal dementia illustrate the differential role of biomarkers based on genotype. Similar advances in amyotrophic lateral sclerosis would transform our understanding of key events in pathogenesis, thereby dramatically accelerating progress towards disease prevention. Deciphering the biology of pre-symptomatic amyotrophic lateral sclerosis relies on a clear conceptual framework for defining the earliest stages of disease. Clinically manifest amyotrophic lateral sclerosis may emerge abruptly, especially among those who harbour genetic mutations associated with rapidly progressive amyotrophic lateral sclerosis. However, the disease may also evolve more gradually, revealing a prodromal period of mild motor impairment preceding phenoconversion to clinically manifest disease. Similarly, cognitive and behavioural impairment, when present, may emerge gradually, evolving through a prodromal period of mild cognitive impairment or mild behavioural impairment before progression to amyotrophic lateral sclerosis. Biomarkers are critically important to studying pre-symptomatic amyotrophic lateral sclerosis and essential to efforts to intervene therapeutically before clinically manifest disease emerges. The use of non-genetic biomarkers, however, presents challenges related to counselling, informed consent, communication of results and limited protections afforded by existing legislation. Experiences from pre-symptomatic genetic testing and counselling, and the legal protections against discrimination based on genetic data, may serve as a guide. Building on what we have learned - more broadly from other pre-symptomatic neurodegenerative diseases and specifically from amyotrophic lateral sclerosis gene mutation carriers - we present a road map to early intervention, and perhaps even disease prevention, for all forms of amyotrophic lateral sclerosis.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Kliest, Tessa, et al.
(författare)
-
Clinical trials in pediatric ALS: a TRICALS feasibility study
- 2022
-
Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Taylor & Francis Group. - 2167-8421 .- 2167-9223. ; 23:7-8, s. 481-488
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA).Objective: To assess the feasibility of clinical studies on the effect of therapy in children (<18 years) with ALS in Europe.Methods: The EMA database was searched for submitted PIPs in ALS. A questionnaire was sent to 58 European ALS centers to collect the prevalence of pediatric ALS during the past ten years, the recruitment potential for future pediatric trials, and opinions of ALS experts concerning a waiver for ALS.Results: Four PIPs were identified; two were waived and two are planned for the future. In total, 49 (84.5%) centers responded to the questionnaire. The diagnosis of 44,858 patients with ALS was reported by 46 sites; 39 of the patients had an onset < 18 years (prevalence of 0.008 cases per 100,000 or 0.087% of all diagnosed patients). The estimated recruitment potential (47 sites) was 26 pediatric patients within five years. A majority of ALS experts (75.5%) recommend a waiver should apply for ALS due to the low prevalence of pediatric ALS.Conclusions: ALS with an onset before 18 years is extremely rare and may be a distinct entity from adult ALS. Conducting studies on the effect of disease-modifying therapy in pediatric ALS may involve lengthy recruitment periods, high costs, ethical/legal implications, challenges in trial design and limited information.
|
|
| 16. |
|
|
