Accelerating evidence generation: Addressing critical challenges and charting a path forward.

Efficient evidence generation to assess the clinical and economic impact of medical therapies is critical amid rising healthcare costs and aging populations. However, drug development and clinical trials remain far too expensive and inefficient for all stakeholders. On October 25-26, 2023, the Duke Clinical Research Institute brought together leaders from academia, industry, government agencies, patient advocacy, and nonprofit organizations to explore how different entities and influencers in drug development and healthcare can realign incentive structures to efficiently accelerate evidence generation that addresses the highest public health needs.

Effectiveness of a Constructed Wetland with Carbon Filtration in Reducing Pesticides Associated with Agricultural Runoff.

The Salinas Valley in Monterey County, California, USA, is a highly productive agricultural region. Irrigation runoff containing pesticides at concentrations toxic to aquatic organisms poses a threat to aquatic ecosystems within local watersheds. This study monitored the effectiveness of a constructed wetland treatment system with a granulated activated carbon (GAC) filter installation at reducing pesticide concentrations and associated toxicity to Ceriodaphnia dubia, Hyalella azteca, and Chironomus dilutus.

Comparison of the Relative Efficacies of Granulated Activated Carbon and Biochar to Reduce Chlorpyrifos and Imidacloprid Loading and Toxicity Using Laboratory Bench Scale Experiments.

Pesticide loads and associated toxicity can be significantly reduced using integrated vegetated treatment systems, which remove moderately soluble and hydrophobic pesticides, but need a sorbent material to remove more soluble pesticides. Neonicotinoids such as imidacloprid are widely used insecticides, acutely toxic, and have been linked to a range of ecological effects. Laboratory experiments were conducted to test the sorptive capacity of granulated activated carbon and biochar for removing imidacloprid and the organophosphate insecticide chlorpyrifos in a scaled-down treatment system.

Changing patterns in water toxicity associated with current use pesticides in three California agriculture regions.

Regulation of agriculture irrigation water discharges in California, USA, is assessed and controlled by its 9 Regional Water Quality Control Boards under the jurisdiction of the California State Water Resources Control Board. Each Regional Water Board has developed programs to control pesticides in runoff as part of the waste discharge requirements implemented through each region's Irrigated Lands Regulatory Program. The present study assessed how pesticide use patterns differ in the Imperial (Imperial County) and the Salinas and Santa Maria (Monterey County) valleys, which host 3 of California's prime agriculture areas.

Vegetated Treatment Systems for Removing Contaminants Associated with Surface Water Toxicity in Agriculture and Urban Runoff.

Urban stormwater and agriculture irrigation runoff contain a complex mixture of contaminants that are often toxic to adjacent receiving waters. Runoff may be treated with simple systems designed to promote sorption of contaminants to vegetation and soils and promote infiltration. Two example systems are described: a bioswale treatment system for urban stormwater treatment, and a vegetated drainage ditch for treating agriculture irrigation runoff.

Carbon Treatment as a Method to Remove Imidacloprid from Agriculture Runoff.

Use of neonicotinoid pesticides is increasing worldwide and there is growing evidence of surface water contamination from this class of insecticide. Due to their high solubility, traditional mitigation practices may be less effective at reducing neonicotinoid concentrations in agricultural runoff. In the current study, laboratory experiments were conducted to determine if granulated activated carbon (GAC) reduces concentrations of the neonicotinoid imidacloprid in water under simulated flow conditions.

An integrated vegetated ditch system reduces chlorpyrifos loading in agricultural runoff.

Agricultural runoff containing toxic concentrations of the organophosphate pesticide chlorpyrifos has led to impaired water body listings and total maximum daily load restrictions in California's central coast watersheds. Chlorpyrifos use is now tightly regulated by the Central Coast Regional Water Quality Control Board. This study evaluated treatments designed to reduce chlorpyrifos in agricultural runoff.

Bioswales reduce contaminants associated with toxicity in urban storm water.

Contamination and toxicity associated with urban storm water runoff are a growing concern because of the potential impacts on receiving systems. California water regulators are mandating implementation of green infrastructure as part of new urban development projects to treat storm water and increase infiltration. Parking lot bioswales are low impact development practices that promote filtering of runoff through plants and soil.

Temporal and spatial trends in sediment contaminants associated with toxicity in California watersheds.

California's Stream Pollution Trends program (SPoT) assesses long-term water quality trends, using 100 base-of-the-watershed sampling sites. Annual statewide sediment surveys from 2008 to 2012 identified consistent levels of statewide toxicity (19%), using the freshwater amphipod Hyalella azteca. Significant contaminant trends included a decrease in PCBs, stable concentrations of metals and PAHs, and a statewide increase in detections and concentrations of pyrethroid pesticides.

The Effects of the Landguard™ A900 Enzyme on the Macroinvertebrate Community in the Salinas River, California, United States of America.

Agricultural use of organophosphate pesticides are responsible for surface water toxicity in California and has led to a number of impaired water body listings under section 303(d) of the Clean Water Act. Integrated passive-treatment systems can reduce pesticide loading in row crop runoff, but they are only partially effective for the more soluble organophosphates. The Landguard™ enzyme has been effectively proven as an on-farm management practice for the removal of chlorpyrifos and diazinon in furrow runoff, but it has not been used in larger-scale treatment because of concerns regarding the potential impact on in-stream macroinvertebrates after chronic use.

Relative toxicity of bifenthrin to Hyalella azteca in 10 day versus 28 day exposures.

Many watersheds in the Central Valley region of California are listed as impaired due to pyrethroid-associated sediment toxicity. The Central Valley Regional Water Quality Control Board is developing numeric sediment quality criteria for pyrethroids, beginning with bifenthrin. Criteria are being developed using existing data, along with data from 10 d and 28 d toxicity tests with Hyalella azteca conducted as part of the current study.

Monitoring the aquatic toxicity of mosquito vector control spray pesticides to freshwater receiving waters.

Pesticides are applied to state and local waterways in California to control insects such as mosquitoes, which are known to serve as a vector for West Nile Virus infection of humans. The California State Water Resources Control Board adopted a National Pollutant Discharge Elimination System General Permit to address the discharge to waters of the United States of pesticides resulting from adult and larval mosquito control. Because pesticides used in spray activities have the potential to cause toxicity to nontarget organisms in receiving waters, the current study was designed to determine whether toxicity testing provides additional, useful environmental risk information beyond chemical analysis in monitoring spray pesticide applications.

Use of semipermeable membrane devices (SPMDs) to characterize dissolved hydrocarbon fractions of both dispersed and undispersed oil.

Crude oil contamination remains a problem along coastal California and its impacts on pelagic organisms are of concern. Previous crude and dispersed oil studies showed a decrease in fish toxicity when Corexit 9500 dispersant was applied. However, observed sublethal metabolic effects were similar for both oil conditions, suggesting fish were accumulating similar dissolved hydrocarbons.

Hypersalinity toxicity thresholds for nine California ocean plan toxicity test protocols.

Currently, several desalination facilities have been proposed to operate or are actually operating in California. These facilities' use of reverse osmosis (RO) may discharge hypersaline reject brine into the marine environment. The risks, if any, this brine would pose to coastal receiving waters are unknown.

Environmental fate of fungicides and other current-use pesticides in a central California estuary.

The current study documents the fate of current-use pesticides in an agriculturally-dominated central California coastal estuary by focusing on the occurrence in water, sediment and tissue of resident aquatic organisms. Three fungicides (azoxystrobin, boscalid, and pyraclostrobin), one herbicide (propyzamide) and two organophosphate insecticides (chlorpyrifos and diazinon) were detected frequently. Dissolved pesticide concentrations in the estuary corresponded to the timing of application while bed sediment pesticide concentrations correlated with the distance from potential sources.

Pyrethroid and organophosphate pesticide-associated toxicity in two coastal watersheds (California, USA).

Portions of the Santa Maria River and Oso Flaco Creek watersheds in central California, USA, are listed as impaired under section 303(d) of the Clean Water Act and require development of total maximum daily load (TMDL) allocations. These listings are for general pesticide contamination, but are largely based on historic monitoring of sediment and fish tissue samples that showed contamination by organochlorine pesticides. Recent studies have shown that toxicity in these watersheds is caused by organophosphate pesticides (water and sediment) and pyrethroid pesticides (sediment).

NMR-based characterization of the acute metabolic effects of weathered crude and dispersed oil in spawning topsmelt and their embryos.

Oil spill responders require information on the relative toxicity of dispersed and un-dispersed oil in order to make informed decisions regarding the use of chemical dispersants during spill events. Toxicity of the water-accommodated fraction (WAF) and the chemically-enhanced WAF (CEWAF; via the dispersant Corexit 9500) of weathered Prudhoe Bay crude oil was investigated using adult and embryonic topsmelt; topsmelt are an ecologically important atherinid in California bays and estuaries and an important indicator species. Following 96-h exposures, metabolite profiles were measured using 1D (1)H nuclear magnetic resonance (NMR) spectroscopy and compared via principal component analysis.

Metabolic responses produced by crude versus dispersed oil in Chinook salmon pre-smolts via NMR-based metabolomics.

Crude oil spills from tankers remain a serious threat along coastal California. Resource managers require information on the acute toxicity of treated and untreated oil, and their sublethal effects on wildlife. This investigation compared the toxic actions of the water-accommodated fraction (WAF) and the chemically-enhanced WAF (CEWAF; Corexit 9500) of Prudhoe Bay crude oil in pre-smolt Chinook salmon (Oncorhynchus tshawytscha) via nuclear magnetic resonance (NMR)-based metabolomics.

Evaluation of methods to determine causes of sediment toxicity in San Diego Bay, California, USA.

Regulation of waterbodies impaired due to sediment toxicity may require development of Total Maximum Daily Load (TMDL) allocations to reduce chemicals of concern. A key step in this process is the identification of chemicals responsible for toxicity, and sediment toxicity identification evaluation procedures (TIEs) are the primary tools used to accomplish this. Several sites in San Diego Bay (CA, USA) are listed as impaired due to sediment toxicity associated with organic chemicals and metals, and due to degraded benthic macroinvertebrate communities.

Characterization of the metabolic actions of crude versus dispersed oil in salmon smolts via NMR-based metabolomics.

With maritime transport of crude oil from Alaska to California, there is significant potential for a catastrophic spill which could impact migrating salmon. Therefore, this study compared the lethal and sublethal metabolic actions of the water-accommodated fraction (WAF) and the chemically enhanced WAF (CEWAF, via Corexit 9500) of Prudhoe Bay crude oil in smolts of Chinook salmon (Onchorhyncus tshawytscha). After 96-h exposure to the CEWAF, the resulting LC50 was some 20 times higher (i.

Evaluation of phase II toxicity identification evaluation methods for freshwater whole sediment and interstitial water.

Phase I whole sediment toxicity identification evaluation (TIE) methods have been developed to characterize the cause of toxicity as organic chemicals, metals, or ammonia. In Phase II identification treatments, resins added to whole sediment to reduce toxicity caused by metals and organics can be separated and eluted much like solid-phase extraction (SPE) columns are eluted for interstitial water. In this study, formulated reference sediments spiked with toxic concentrations of copper, fluoranthene, and nonylphenol were subjected to whole sediment and interstitial water TIE treatments to evaluate Phase I and II TIE procedures for identifying the cause of toxicity to Hyalella azteca.

Preliminary investigation of the effects of dispersed Prudhoe Bay Crude Oil on developing topsmelt embryos, Atherinops affinis.

Static exposure experiments were conducted to assess the toxicity of dispersed Prudhoe Bay Crude Oil (PBCO) to embryos of the topsmelt (Atherinops affinis). Treatment with the dispersant COREXIT 9500 resulted in greater hydrocarbon concentrations in chemically enhanced water-accommodated fractions (CEWAFs) of oil, relative to the untreated water-accommodated fractions (WAFs). Topsmelt embryo development and survival to hatching was significantly inhibited in CEWAF tests while minimal effects on embryo-larval survival were observed in WAF tests.

Statewide investigation of the role of pyrethroid pesticides in sediment toxicity in California's urban waterways.

A statewide investigation of urban creek sediment toxicity was conducted in California in recognition of increased incidences of toxicity linked to pyrethroid pesticides. The goals were to examine the spatial occurrence and magnitude of sediment toxicity in California urban creeks, and to examine the role of pyrethroids in toxic urban creek sediment samples. After a preliminary screening of 90 sites, 30 creeks were sampled in eight geographical regions.

Applications of carboxylesterase activity in environmental monitoring and toxicity identification evaluations (TIEs).

This review has examined a number of issues surrounding the use of carboxylesterase activity in environmental monitoring. It is clear that carboxylesterases are important enzymes that deserve increased study. This class of enzymes appears to have promise for employment in environmental monitoring with a number of organisms and testing scenarios, and it is appropriate for inclusion in standard monitoring assays.

Relative sensitivities of toxicity test protocols with the amphipods Eohaustorius estuarius and Ampelisca abdita.

A series of dose-response experiments was conducted to compare the relative sensitivities of toxicity test protocols using the amphipods Ampelisca abdita and Eohaustorius estuarius. A. abdita is one of the dominant infaunal species in the San Francisco Estuary, and E.