The influence of tidal inlet migration and closure on barrier planform changes : Federal Beach, NC

Federal Beach, a narrow 10 km-long barrier spit that connects the Fort Fisher headland and the Cape Fear foreland, has been breached numerous times during the past centuries. Prior to 1880 the storm breaches served as one of several conduits for the exchange/discharge of the Cape Fear River. One long-lasting breach that opened in 1761 near the headland evolved into the second largest inlet system in the area until it was artificially closed by the U.S. Army Corps. of Engineers in 1880. Closure was accomplished by the construction of a 4.6 km-long dam that dramatically reduced the tidal prism and the extent of the ebb tidal delta. Long-lasting impacts associated with inlet closure include the chronic erosion of the headland area and frequent breaching of the barrier and the subsequent rapid migration of small inlets. Concurrent with inlet migration is the realignment of the barrier spit shoreline. A GIS-based analysis of aerial photographs from 1938 to 2005 was conducted to quantify shoreline rate-of-change values for the barrier spit, and migration rates of the associated inlet systems. The Federal Beach barrier spit shoreline accreted an average of 6 m, at a rate of 0.1 m/yr during this period. This study identifies two shoreline change zones (SCZ). SCZ I is characterized as a retrograding reach, with long-term erosion averaging 78 m from 1945 to 2005. Over the same period, SCZ II is characterized as a prograding reach, with long-term accretion averaging 69 m. Two inlet systems, New Inlet A (NIA) and New Inlet B (NIB) were active along the Federal Beach barrier from 1938 to 1999. The NIA system opened in the 1890’s and by 1959 had migrated approximately 6 km to the south where the system closed due to shoaling of the inlet throat. New Inlet B opened in 1944 and closed in 1999. During this period the NIB system migrated south a total of 6 km, at a mean rate of 106 m/yr. Both the size and stability of the New Inlet B system was determined to be strongly influenced by the morphology of the backbarrier environment with respect to inlet position. As both of the New Inlet systems migrate along Federal Beach they actively reshape the barrier spit planform, resulting in the progradation of the updrift barrier shoreline. Anthropogenic and natural changes to the backbarrier environment have impacted the behavior of the inlet systems, consequently resulting in long-term changes of the Federal Beach barrier spit planform

Gene Therapy in a Humanized Mouse Model of Familial Hypercholesterolemia Leads to Marked Regression of Atherosclerosis

Familial hypercholesterolemia (FH) is an autosomal codominant disorder caused by mutations in the low-density lipoprotein receptor (LDLR) gene. Homozygous FH patients (hoFH) have severe hypercholesterolemia leading to life threatening atherosclerosis in childhood and adolescence. Mice with germ line interruptions in the Ldlr and Apobec1 genes (Ldlr(-/-)Apobec1(-/-)) simulate metabolic and clinical aspects of hoFH, including atherogenesis on a chow diet.In this study, vectors based on adeno-associated virus 8 (AAV8) were used to deliver the gene for mouse Ldlr (mLDLR) to the livers of Ldlr(-/-)Apobec1(-/-) mice. A single intravenous injection of AAV8.mLDLR was found to significantly reduce plasma cholesterol and non-HDL cholesterol levels in chow-fed animals at doses as low as 3×10(9) genome copies/mouse. Whereas Ldlr(-/-)Apobec1(-/-) mice fed a western-type diet and injected with a control AAV8.null vector experienced a further 65% progression in atherosclerosis over 2 months compared with baseline mice, Ldlr(-/-)Apobec1(-/-) mice treated with AAV8.mLDLR realized an 87% regression of atherosclerotic lesions after 3 months compared to baseline mice. Immunohistochemical analyses revealed a substantial remodeling of atherosclerotic lesions.Collectively, the results presented herein suggest that AAV8-based gene therapy for FH may be feasible and support further development of this approach. The pre-clinical data from these studies will enable for the effective translation of gene therapy into the clinic for treatment of FH