Haemophilia is a rare disease for which the approved therapeutic options have remained virtually unchanged for 50 years. In the past decade, however, there has been an explosion of innovation in the treatment options that are either in development or have been approved for haemophilia, including engineered clotting factors and an extensive pipeline of new approaches and modalities. Several of these new modalities, especially gene therapy, demonstrate proof of principle in haemophilia but could have broader applications. These advances, in combination with better diagnostics, are now enabling clinicians to improve the standard of care for people with haemophilia. The different mechanisms of action and modifications used in these therapies have implications for their safe and efficacious use, which must be balanced with their therapeutic utility. This Review focuses on the biological aspects of the most advanced and innovative approaches for haemophilia treatment and considers their future use.
The response of Japanese beech (Fagusjaponica Maxim.) sprouts to canopy gaps in natural beech forest in central Japan was studied using two contrasted gaps in which tree-ring chronologies of regenerating stems were analyzed. The gaps were created by uprooting of a single Quercus mongolica var. grosseserrata stem (diameter: 50 cm; gap size: 40 m2; 23 years old) and by concurrent uprootings of four E japonica stools (gap size: 180 m2; 30 years old).Japanese beech sprouts emerged before and after the gap formation and dominated stem populations in both gaps. In gaps, growth of F. japonica sprouts was equal or lower than growth of stems of seed origin, but most sprouts (E japonica, Acer mono var. marmoratum) appeared a few years before emergence of seedlings. The small gap created by single stem fall was dominated by some beech sprouts from stools adjacent to the gap. The multiple gap was not closed by beech sprouts from stools surrounding the gap, but some dominant beech stems were resprouts from the uprooted beech stools. The existence of a 'sprout bank' under the canopy may play an important role in the closing process of gaps in natural Japanese beech forest.
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