FROM RECHARGE TO REEF: ASSESSING THE SOURCES, QUANTITY, AND TRANSPORT OF GROUNDWATER ON TUTUILA ISLAND, AMERICAN SAMOA

Ph.D.Ph.D. Thesis. University of Hawaiʻi at Mānoa 201

Increased matrix synthesis following adenoviral transfer of a transforming growth factor beta1 gene into articular chondrocytes

Monolayer cultures of lapine articular chondrocytes were transduced with first-generation adenoviral vectors carrying lacZ or transforming growth factor β1 genes under the transcriptional control of the human cytomegalovirus early promoter. High concentrations of transforming growth factor β1 were produced by chondrocytes following transfer of the transforming growth factor β1 gene but not the lacZ gene. Transduced chondrocytes responded to the elevated endogenous production of transforming growth factor β1 by increasing their synthesis of proteoglycan, collagen, and noncollagenous proteins in a dose-dependent fashion. The increases in collagen synthesis were not accompanied by alterations in the collagen phenotype; type-II collagen remained the predominant collagen. Transforming growth factor β1 could not, however, rescue the collagen phenotype of cells that had undergone phenotypic modulation as a result of serial passaging. These data demonstrate that chondrocytes can be genetically manipulated to produce and respond to the potentially therapeutic cytokine transforming growth factor β1. This technology has a number of experimental and therapeutic applications, including those related to the study and treatment of arthritis and cartilage repair

Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1

OBJECTIVE: To assess the safety and efficacy of ixekizumab, a monoclonal antibody that inhibits interleukin-17A, in a double-blind phase III trial enrolling patients with active psoriatic arthritis (PsA). METHODS: Patients naive to biologic therapy with active PsA were randomised to subcutaneous injections of placebo (N=106), adalimumab 40 mg once every 2 weeks (active reference; N=101), ixekizumab 80 mg once every 2 weeks (IXEQ2W) (N=103), or ixekizumab 80 mg once every 4 weeks (IXEQ4W) (N=107). Both ixekizumab regimens included a 160-mg starting dose. The primary objective was to assess the superiority of IXEQ2W or IXEQ4W versus placebo as measured by the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response at week 24. RESULTS: Significantly more patients treated with ixekizumab achieved an ACR20 response with IXEQ2W (62.1%) or IXEQ4W (57.9%) than placebo (30.2%) (p≤0.001; non-responder imputation method). Disease activity and functional disability were significantly improved with both ixekizumab doses versus placebo at weeks 12 and 24, and there was significantly less progression of structural damage at week 24 (p≤0.01). Clearance of plaque psoriasis was greater with ixekizumab than placebo (p≤0.001). Efficacy results with adalimumab, the active reference arm, showed significant improvements versus placebo. Treatment-emergent adverse events were more frequent with ixekizumab (65.7-66.4%) and adalimumab (64.4%) than placebo (47.2%) (p<0.05). CONCLUSIONS: In biologic-naive patients with active PsA, ixekizumab treatment resulted in improvements in disease activity and physical function, as well as in the inhibition of structural damage progression. Overall, adverse events were more frequent in all active groups compared with placebo

Ridge to reef management implications for the development of an open-source dissolved inorganic nitrogen-loading model in American Samoa

Excessive nutrient discharge to tropical island coastlines drives eutrophication and algal blooms with significant implications for reef ecosystem condition and provision of ecosystem services. Management actions to address nutrient pollution in coastal ecosystems include setting water-quality standards for surface waters discharging to the coast. However, these standards do not account for the effects of groundwater discharge, variability in flow, or dilution, all of which may influence the assessment of true nutrient impacts on nearshore reef habitats. We developed a method to estimate dissolved inorganic nitrogen (DIN) loads to coastal zones by integrating commonly available datasets within a geospatial modeling framework for Tutuila, American Samoa. The DIN-loading model integrated an open-source water budget model, water-sampling results, and publicly available streamflow data to predict watershed-scale DIN loading to the island’s entire coastline. Submarine groundwater discharge (SGD) was found to deliver more terrigenous DIN to the coastal zone than surface water pathways, supporting findings from other tropical islands. On-site wastewater disposal systems were also found to be the primary anthropogenic sources of DIN to coastal waters. Our island-wide DIN-loading model provides a simple and robust metric to define spatially explicit sources and delivery mechanisms of nutrient pollution to nearshore reef habitats. Understanding the sources and primary transport modes of inorganic nitrogen to nearshore reef ecosystems can help coastal resource managers target the most impactful human activities in the most vulnerable locations, thereby increasing the adaptive capacity of unique island ecosystems to environmental variation and disturbances

Metal Mobilization As An Effect of Anthropogenic Contamination in Groundwater Aquifers in Tutuila, American Samoa

Groundwater is the primary drinking water source on most oceanic islands, including Tutuila, American Samoa. Drinking water quality on Tutuila is impacted by anthropogenic pollution sources such as on-site sewage disposal systems, piggeries, and agricultural leachate, particularly across the densely populated Tafuna&ndash;Leone Plain. The remineralization of anthropogenically sourced organic matter produces nitrate and dissolved inorganic carbon, which, according to previously published studies, have the potential to mobilize naturally occurring metals. This study provides further evidence that nutrients and dissolved inorganic carbon, along with naturally sourced metal concentrations, become elevated along pollution gradients and show correlation with each other. Across the Tafuna&ndash;Leone Plain, nitrate concentrations have a moderately positive correlation with uranium and vanadium. Dissolved inorganic carbon also positively correlate with nitrate, uranium, and vanadium. Similar studies elsewhere suggest that, in addition to nitrate, organic matter remineralization associated with carbonate create conditions to favor natural metal mobilization. Correlation analysis results imply that, while the surveyed trace metals are likely naturally sourced, some become soluble and more mobile in the presence of anthropogenically sourced nitrate and dissolved inorganic carbon, which alters redox conditions in the aquifer

Assessment of Terrigenous Nutrient Loading to Coastal Ecosystems along a Human Land-Use Gradient, Tutuila, American Samoa

Anthropogenic nutrient loading is well recognized as a stressor to coastal ecosystem health. However, resource managers are often focused on addressing point source or surface water discharge, whereas the impact of submarine groundwater discharge (SGD) as a nutrient vector is often unappreciated. This study examines connections between land use and nutrient loading through comparison of four watersheds and embayments spanning a gradient of human use impact on Tutuila, a high tropical oceanic island in American Samoa. In each study location, coastal radon-222 measurements, dissolved nutrient concentrations, and nitrogen isotope values (&#948;15N) in water and in situ macroalgal tissue were used to explore SGD and baseflow derived nutrient impacts, and to determine probable nutrient sources. In addition to sampling in situ macroalgae, pre-treated macroalgal specimens were deployed throughout each embayment to uptake ambient nutrients and provide a standardized assessment of differences between locations. Results show SGD-derived nutrient flux was more significant than baseflow nutrient flux in all watersheds, and &#948;15N values in water and algae suggested wastewater or manure are likely sources of elevated nutrient levels. While nutrient loading correlated well with expected anthropogenic impact, other factors such as differences in hydrogeology, distribution of development, and wastewater infrastructure also likely play a role in the visibility of impacts in each watershed

Catchment to sea connection: impacts of terrestrial run-off on benthic ecosystems in American Samoa

Variation in water quality can directly affect the composition of benthic assemblages on coral reefs. Yet, few studies have directly quantified nutrient and suspended particulate matter (SPM) to examine their potential impacts on benthic community structure, especially around high oceanic islands. We assessed the spatio-temporal variation of nutrients and SPM across six sites in American Samoa over a 12-month period and used exploratory path analysis to relate dissolved inorganic nutrients, land use, and natural and anthropogenic drivers to benthic assemblages on adjacent shallow reefs. Multivariate analyses showed clear gradients in nutrient concentrations, sediment accumulation and composition, and benthic structure across watersheds. Instream nutrients and land uses positively influenced reef flat nutrient concentrations, while benthic assemblages were best predicted by wave exposure, runoff, stream phosphate and dissolved inorganic nitrogen loads. Identifying locality-specific drivers of water quality and benthic condition can support targeted management in American Samoa and in other high islands