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- Mercuri, E., et al.
(författare)
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Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study
- 2020
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Ingår i: Journal of Comparative Effectiveness Research. - : Becaris Publishing Limited. - 2042-6305 .- 2042-6313. ; 9:5, s. 341-360
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). We examined the effectiveness of ataluren + standard of care (SoC) in the registry versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS), DMD genotype-phenotype/-ataluren benefit correlations and ataluren safety. Patients & methods: Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established disease progression predictors (registry cut-off date, 9 July 2018). Results & conclusion: Kaplan-Meier analyses demonstrated that ataluren + SoC significantly delayed age at loss of ambulation and age at worsening performance in timed function tests versus SoC alone (p <= 0.05). There were no DMD genotype-phenotype/ataluren benefit correlations. Ataluren was well tolerated. These results indicate that ataluren + SoC delays functional milestones of DMD progression in patients with nmDMD in routine clinical practice. ClinicalTrials.gov identifier: NCT02369731. ClinicalTrials.gov identifier: NCT02369731.
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- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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- Steffen, A., et al.
(författare)
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A synthesis of atmospheric mercury depletion event chemistry in the atmosphere and snow
- 2008
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 8:6, s. 1445-1482
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Tidskriftsartikel (refereegranskat)abstract
- It was discovered in 1995 that, during the spring time, unexpectedly low concentrations of gaseous elemental mercury (GEM) occurred in the Arctic air. This was surprising for a pollutant known to have a long residence time in the atmosphere; however conditions appeared to exist in the Arctic that promoted this depletion of mercury (Hg). This phenomenon is termed atmospheric mercury depletion events (AMDEs) and its discovery has revolutionized our understanding of the cycling of Hg in Polar Regions while stimulating a significant amount of research to understand its impact to this fragile ecosystem. Shortly after the discovery was made in Canada, AMDEs were confirmed to occur throughout the Arctic, sub-Artic and Antarctic coasts. It is now known that, through a series of photochemically initiated reactions involving halogens, GEM is converted to a more reactive species and is subsequently associated to particles in the air and/or deposited to the polar environment. AMDEs are a means by which Hg is transferred from the atmosphere to the environment that was previously unknown. In this article we review Hg research taken place in Polar Regions pertaining to AMDEs, the methods used to collect Hg in different environmental media, research results of the current understanding of AMDEs from field, laboratory and modeling work, how Hg cycles around the environment after AMDEs, gaps in our current knowledge and the future impacts that AMDEs may have on polar environments. The research presented has shown that while considerable improvements in methodology to measure Hg have been made but the main limitation remains knowing the speciation of Hg in the various media. The processes that drive AMDEs and how they occur are discussed. As well, the role that the snow pack and the sea ice play in the cycling of Hg is presented. It has been found that deposition of Hg from AMDEs occurs at marine coasts and not far inland and that a fraction of the deposited Hg does not remain in the same form in the snow. Kinetic studies undertaken have demonstrated that bromine is the major oxidant depleting Hg in the atmosphere. Modeling results demonstrate that there is a significant deposition of Hg to Polar Regions as a result of AMDEs. Models have also shown that Hg is readily transported to the Arctic from source regions, at times during springtime when this environment is actively transforming Hg from the atmosphere to the snow and ice surfaces. The presence of significant amounts of methyl Hg in snow in the Arctic surrounding AMDEs is important because this species is the link between the environment and impacts to wildlife and humans. Further, much work on methylation and demethylation processes has occurred but these processes are not yet fully understood. Recent changes in the climate and sea ice cover in Polar Regions are likely to have strong effects on the cycling of Hg in this environment; however more research is needed to understand Hg processes in order to formulate meaningful predictions of these changes.
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