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- Jakobsson, Martin, et al.
(författare)
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Arctic Ocean Bathymetry : A Necessary Geospatial Framework
- 2015
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Ingår i: Arctic. - : The Arctic Institute of North America. - 0004-0843 .- 1923-1245. ; 68, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- Most ocean science relies on a geospatial infrastructure that is built from bathymetry data collected from ships underway, archived, and converted into maps and digital grids. Bathymetry, the depth of the seafloor, besides having vital importance to geology and navigation, is a fundamental element in studies of deep water circulation, tides, tsunami forecasting, upwelling, fishing resources, wave action, sediment transport, environmental change, and slope stability, as well as in site selection for platforms, cables, and pipelines, waste disposal, and mineral extraction. Recent developments in multibeam sonar mapping have-so dramatically increased the resolution with which the seafloor can be portrayed that previous representations must be considered obsolete. Scientific conclusions based on sparse bathymetric information should be re-examined and refined. At this time only about 11% of the Arctic Ocean has been mapped with multibeam; the rest of its seafloor area is portrayed through mathematical interpolation using a very sparse depth-sounding database. In order for all Arctic marine activities to benefit fully from the improvement that multibeam provides, the entire Arctic Ocean must be multibeam-mapped, a task that can be accomplished only through international coordination and collaboration that includes the scientific community, naval institutions, and industry.
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| 3. |
- Pipe, Steven W., et al.
(författare)
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Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B
- 2023
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 388:8, s. 706-718
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Tidskriftsartikel (refereegranskat)abstract
- Background: Moderate-to-severe hemophilia B is treated with lifelong, continuous coagulation factor IX replacement to prevent bleeding. Gene therapy for hemophilia B aims to establish sustained factor IX activity, thereby protecting against bleeding without burdensome factor IX replacement. Methods: In this open-label, phase 3 study, after a lead-in period (≥6 months) of factor IX prophylaxis, we administered one infusion of adeno-associated virus 5 (AAV5) vector expressing the Padua factor IX variant (etranacogene dezaparvovec; 2×1013 genome copies per kilogram of body weight) to 54 men with hemophilia B (factor IX activity ≤2% of the normal value) regardless of preexisting AAV5 neutralizing antibodies. The primary end point was the annualized bleeding rate, evaluated in a noninferiority analysis comparing the rate during months 7 through 18 after etranacogene dezaparvovec treatment with the rate during the lead-in period. Noninferiority of etranacogene dezaparvovec was defined as an upper limit of the two-sided 95% Wald confidence interval of the annualized bleeding rate ratio that was less than the noninferiority margin of 1.8. Superiority, additional efficacy measures, and safety were also assessed. Results: The annualized bleeding rate decreased from 4.19 (95% confidence interval [CI], 3.22 to 5.45) during the lead-in period to 1.51 (95% CI, 0.81 to 2.82) during months 7 through 18 after treatment, for a rate ratio of 0.36 (95% Wald CI, 0.20 to 0.64; P<0.001), demonstrating noninferiority and superiority of etranacogene dezaparvovec as compared with factor IX prophylaxis. Factor IX activity had increased from baseline by a least-squares mean of 36.2 percentage points (95% CI, 31.4 to 41.0) at 6 months and 34.3 percentage points (95% CI, 29.5 to 39.1) at 18 months after treatment, and usage of factor IX concentrate decreased by a mean of 248,825 IU per year per participant in the post-treatment period (P<0.001 for all three comparisons). Benefits and safety were observed in participants with predose AAV5 neutralizing antibody titers of less than 700. No treatment-related serious adverse events occurred. Conclusions: Etranacogene dezaparvovec gene therapy was superior to prophylactic factor IX with respect to the annualized bleeding rate, and it had a favorable safety profile.
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