Long‐term evolution of the Old Rhine estuary : unraveling effects of changing boundary conditions and inherited landscape.

The long‐term morphodynamic evolution of estuaries depends on a combination of antecedent topography and boundary conditions, including fluvial input, sea‐level change and regional‐landscape interactions. Identifying effects of such boundary conditions on estuary evolution is important to anticipate future changes in specific boundary conditions and for hindcasting with numerical and physical models. A comprehensive synthesis of the evolution of the former Old Rhine estuary is presented here, together with its boundary conditions over its full lifespan from 6,500 to 1,000 cal. yr bp. This system formed during a period of sea‐level high stand, during which the estuary served as the main River Rhine outlet. The estuary went through three stages of evolution: a maturation phase in a wide infilling back‐barrier basin, a stable mature phase and an abandoning phase, both in a laterally confined setting. The Old Rhine River formed by a river avulsion around 6,500 cal. yr bp that connected to a tidal channel within a large back‐barrier basin. Decelerating sea‐level rise caused the back‐barrier basin to silt up around 5,700 cal. yr bp, resulting in shoreline progradation by beach‐barrier formation until ∼2,000 cal. yr bp. Beach‐barrier formation along the coast and natural levee formation along the river triggered peat formation in the coastal plain, laterally constraining the estuary and limiting overbank deposition, which caused most sediment to accumulate offshore. The abandoning phase started around 2,200 cal. yr bp when a series of upstream avulsions led to a substantial reduction in fluvial input. This induced a period of enhanced estuarine overbank clay deposition that continued into near‐complete silting up and estuary closure around 1200 ad. These findings exemplify how tidal systems, formed in wide coastal plains during sea‐level high stand, depend on antecedent conditions, and how they respond to connection and disconnection of a large river over long, millennial timescales

Improving the translation of animal ischemic stroke studies to humans

Despite testing more than 1026 therapeutic strategies in models ischemic stroke and 114 therapies in human ischemic stroke, only one agent tissue plasminogen activator has successfully been translated to clinical practice as a treatment for acute stroke. Though disappointing, this immense body of work has led to a rethinking of animal stroke models and how to better translate therapies to patients with ischemic stroke. Several recommendations have been made, including the STAIR recommendations and statements of RIGOR from the NIH / NINDS. In this commentary we discuss additional aspects that may be important to improve the translational success of ischemic stroke therapies. These include use of tissue plasminogen activator in animal studies; modeling ischemic stroke heterogeneity in terms of infarct size and cause of human stroke; addressing the confounding effect of anesthesia; use of comparable therapeutic dosage between humans and animals based on biological effect; modeling the human immune system; and developing outcome measures in animals comparable to those used in human stroke trials. With additional study and improved animal modeling of factors involved in human ischemic stroke, we are optimistic that new therapies for the treatment of acute ischemic stroke will be developed

Molecular, cellular and functional events in axonal sprouting after stroke

Stroke is the leading cause of adult disability. Yet there is a limited degree of recovery in this disease. One of the mechanisms of recovery is the formation of new connections in the brain and spinal cord after stroke: post-stroke axonal sprouting. Studies indicate that post-stroke axonal sprouting occurs in mice, rats, primates and humans. Inducing post-stroke axonal sprouting in specific connections enhances recovery; blocking axonal sprouting impairs recovery. Behavioral activity patterns after stroke modify the axonal sprouting response. A unique regenerative molecular program mediates this aspect of tissue repair in the CNS. The types of connections that are formed after stroke indicate three patterns of axonal sprouting after stroke: Reactive, Reparative and Unbounded Axonal Sprouting. These differ in mechanism, location, relationship to behavioral recovery and, importantly, in their prospect for therapeutic manipulation to enhance tissue repair