An Assessment of Southeast United States Headwater Tidal Creek Sediment Contamination Over a Twenty-Year Period in Relation to Coastal Development.

Headwater tidal creeks are a primary link between estuarine and upland habitats, serving as conduits for runoff. They are sentinel habitats, providing early warning of potential harm, thus ideal systems to evaluate the effects of coastal suburban and urban development on environmental quality. Estuarine sediments have concentrations of metals, polycyclic aromatic hydrocarbons (PAHs), pesticides, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) that are associated with human activity. High concentrations of contaminants can impair faunal communities, habitat quality, and ecosystem function. Forty-three headwater creeks were sampled between 1994 and 2006 to assess contaminants, and 18 of these were sampled again in 2014/2015. Watersheds were classified as forested, forested to suburban, suburban, or urban land. These values are based on their percent impervious cover (IC) levels and change in IC from 1994-2014. Analyses of temporal data resulted in significant relationships between IC and select metals, PAHs, pesticides, PCBs, and PBDEs. In addition, 11 of the creeks sampled in 2014/2015 have paired data from 1994/1995, allowing for change analysis over the 20 years. Results indicated increasing chemical contamination occurring with increasing levels of development, although only PAHs and total dichloro-diphenyl-trichloroethane (DDT) exhibited a statistically significant increase over time; PAHs also exhibited significantly higher concentrations in developed creeks. Additionally, several metals were deemed enriched in developed creeks based on reference conditions. These results expand our knowledge of how these systems respond to urban development and can inform managers about how human population growth along coastlines may predict altered tidal creek health.

A phase 1/2a dose-escalation study of oligodendrocyte progenitor cells in individuals with subacute cervical spinal cord injury.

OBJECTIVE: The primary objective of this study was to evaluate the safety of 3 escalating doses of oligodendrocyte progenitor cells (LCTOPC1; previously known as GRNOPC1 and AST-OPC1) administered at a single time point between 21 and 42 days postinjury to participants with subacute cervical spinal cord injuries (SCIs). The secondary objective was to evaluate changes in neurological function following administration of LCTOPC1. METHODS: This study was designed as an open-label, dose-escalation, multicenter clinical trial. Twenty-five participants with C4-7 American Spinal Injury Association Impairment Scale grade A or B injuries received a single dose of either 2 × 106, 1 × 107, or 2 × 107 LCTOPC1 delivered via intraparenchymal injection into the spinal cord at the site of injury using a custom-designed syringe positioning device. Low-dose tacrolimus was administered until day 60. Outcome measures included adverse event (AE) monitoring and neurological function as measured by the International Standards for Neurological Classification of Spinal Cord Injury. RESULTS: All 25 participants experienced at least one AE, with a total of 534 AEs (32 study-related vs 502 study-unrelated anticipated complications of SCI) reported at the completion of 1-year follow-up. There were 29 serious AEs reported. Two grade 3 serious AEs (CSF leak in one participant and a bacterial infection in another) were considered related to the injection procedure and to immunosuppression with tacrolimus, respectively. The CSF leakage resolved with sequelae, including self-limited altered mental status, and the infection resolved with antibiotic therapy. For all participants, MRI scans demonstrated no evidence of an enlarging mass, spinal cord damage related to the injection procedure, inflammatory lesions in the spinal cord, or masses in the ventricular system. At 1-year follow-up, 21/22 (96%) of the intention-to-treat group recovered one or more levels of neurological function on at least one side of their body, and 7/22 (32%) recovered two or more levels of neurological function on at least one side of their body. CONCLUSIONS: LCTOPC1 can be safely administered to participants in the subacute period after cervical SCI. The injection procedure, low-dose temporary immunosuppression regimen, and LCTOPC1 were well tolerated. The safety and neurological function data support further investigation to determine the efficacy of LCTOPC1 in the treatment of SCI. Clinical trial registration no.: NCT02302157 (ClinicalTrials.gov).

Acute Toxicity of Eight Aqueous Film-Forming Foams to 14 Aquatic Species.

Researchers have developed numerous per- and polyfluoroalkyl substances (PFAS)-free aqueous film-forming foam (AFFF) formulations to replace PFAS-containing AFFF used for fire suppression. As part of the Department of Defense's Strategic Environmental Research and Development Program (SERDP), we examined the direct lethal effects of seven PFAS-free AFFF and a PFAS-containing AFFF on 14 aquatic species using a series of lethal concentration (LC50) tests. We assessed the LC10, LC50, and LC90 values using log-logistic and logit analyses. Across all aquatic species tested, we discovered that exposure to at least one PFAS-free AFFF was more or as toxic as exposure to the PFAS-containing AFFF. For most cases, National Foam Avio F3 Green KHC 3% and Buckeye Platinum Plus C6MILSPEC 3% were the most and least toxic formulations, respectively. Moreover, we found consistency among results from multiple experiments using the same minnow species (Pimephales promelas) and among closely related taxa (e.g., daphnids, amphibians). Lastly, the LC50 values for AFFF formulations trended lower for tested marine species as compared to those of freshwater species. These results dramatically increase the current knowledge on the potentially toxic effects of AFFF but also highlight the need for additional research and the development of new PFAS-free AFFF that are more "ecologically friendly" than those containing persistent PFAS.

Ten-year safety of pluripotent stem cell transplantation in acute thoracic spinal cord injury.

OBJECTIVE: The purpose of this study was to evaluate the safety of oligodendrocyte progenitor cells (LCTOPC1) derived from human pluripotent stem cells administered between 7 and 14 days postinjury to patients with T3 to T11 neurologically complete spinal cord injury (SCI). The rationale for this first-in-human trial was based on evidence that administration of LCTOPC1 supports survival and potential repair of key cellular components and architecture at the SCI site. METHODS: This study was a multisite, open-label, single-arm interventional clinical trial. Participants (n = 5) received a single intraparenchymal injection of 2 × 106 LCTOPC1 caudal to the epicenter of injury using a syringe positioning device. Immunosuppression with tacrolimus was administered for a total of 60 days. Participants were followed with annual in-person examinations and MRI for 5 years at the time of this report and will be followed with annual telephone questionnaires for 6 to 15 years postinjection. The primary endpoint was safety, as measured by the frequency and severity of adverse events related to the LCTOPC1 injection, the injection procedure, and/or the concomitant immunosuppression administered. The secondary endpoint was neurological function as measured by sensory scores and lower-extremity motor scores as measured by the International Standards for Neurological Classification of Spinal Cord Injury examinations. RESULTS: No unanticipated serious adverse events related to LCTOPC1 have been reported with 98% follow-up of participants (49 of 50 annual visits) through the first 10 years of the clinical trial. There was no evidence of neurological decline, enlarging masses, further spinal cord damage, or syrinx formation. MRI results during the long-term follow-up period in patients administered LCTOPC1 cells showed that 80% of patients demonstrated T2 signal changes consistent with the formation of a tissue matrix at the injury site. CONCLUSIONS: This study provides crucial first-in-human safety data supporting the pursuit of future human embryonic stem cell-derived therapies. While we cannot exclude the possibility of future adverse events, the experience in this trial provides evidence that this cell type can be well tolerated by patients, with an event-free period of up to 10 years. Based on the safety profile of LCTOPC1 obtained in this study, a cervical dose escalation trial was initiated (NCT02302157).

Safety of direct injection of oligodendrocyte progenitor cells into the spinal cord of uninjured Göttingen minipigs.

OBJECTIVE: This study was conducted as a final proof-of-safety direct injection of oligodendrocyte progenitor cells into the uninjured spinal cord prior to translation to the human clinical trials. METHODS: In this study, 107 oligodendrocyte progenitor cells (LCTOPC1, also known as AST-OPC1 and GRNOPC1) in 50-µL suspension were injected directly into the uninjured spinal cords of 8 immunosuppressed Göttingen minipigs using a specially designed stereotactic delivery device. Four additional Göttingen minipigs were given Hanks' Balanced Salt Solution and acted as the control group. RESULTS: Cell survival and no evidence of histological damage, abnormal inflammation, microbiological or immunological abnormalities, tumor formation, or unexpected morbidity or mortality were demonstrated. CONCLUSIONS: These data strongly support the safety of intraparenchymal injection of LCTOPC1 into the spinal cord using a model anatomically similar to that of the human spinal cord. Furthermore, this research provides guidance for future clinical interventions, including mechanisms for precise positioning and anticipated volumes of biological payloads that can be safely delivered directly into uninjured portions of the spinal cord.

Assessment of the efficacy of six field cleaning protocols for hydrocarbon quantification.

The defensibility of field sampling data collected in support of natural resource damage assessments and other environmental investigations depends on rigorous quality assurance and control both in the field and laboratory. One important step in field procedures is the cleaning of sampling equipment between samples to minimize the carryover of contaminants. Large-scale sampling efforts during the Deepwater Horizon oil spill event have highlighted the importance of understanding how multiple equipment cleaning protocols affect interstation cross-contamination and the resulting chemical data quality. In this study, six field cleaning techniques were tested on metal sampling equipment using two different sediment types spiked with crude oil in order to understand their relative and absolute effectiveness in reducing chemical carryover. The complexity of the cleaning protocols ranged from a simple water and scrub brush application to protocols that included soap and/or solvent. In this study, percent residual hydrocarbon transfer, relative to total loading in sediments, never exceeded 0.032%. The least labor-intensive protocol, water and scrub brush application, had the highest potential for hydrocarbon transfer (0.011-0.032%). Statistical differences were observed among treatments, and it was found that protocols containing a solvent step were more effective than protocols without solvents. Depending on the data quality objectives, the differences may not be meaningful, and choosing a cleaning technique should be governed by health, safety, and environmental factors. The residual hydrocarbons measured after equipment cleanings for all techniques in this study were negligible when compared with other variables that occur during routine sampling and laboratory activities.

Multi-stressor Effects of Ultraviolet Light, Temperature, and Salinity on Louisiana Sweet Crude Oil Toxicity in Larval Estuarine Organisms.

When oil is spilled into the environment its toxicity is affected by abiotic conditions. The cumulative and interactive stressors of chemical contaminants and environmental factors are especially relevant in estuaries where tidal fluctuations cause wide variability in salinity, temperature, and ultraviolet (UV) light penetration, which is an important modifying factor for polycyclic aromatic hydrocarbon (PAH) toxicity. Characterizing the interactions of multiple stressors on oil toxicity will improve prediction of environmental impacts under various spill scenarios. This study examined changes in crude oil toxicity with temperature, salinity, and UV light. Oil exposures included high-energy, water-accommodated fractions (HEWAFs) and thin oil sheens. Larval (24-48 h post hatch) estuarine species representing different trophic levels and habitats were evaluated. Mean 96 h LC50 values for oil prepared as a HEWAF and tested under standard conditions (20 ppt, 25 °C, No-UV) were 62.5 µg/L tPAH50 (mud snails), 198.5 µg/L (grass shrimp), and 774.5 µg/L (sheepshead minnows). Thin oil sheen 96 h LC50 values were 5.3 µg/L tPAH50 (mud snails), 14.7 µg/L (grass shrimp), and 22.0 µg/L (sheepshead minnows) under standard conditions. UV light significantly increased the toxicity of oil in all species tested. Oil toxicity also was greater under elevated temperature and lower salinity. Multi-stressor (oil combined with either increased temperature, decreased salinity, or both) LC50 values were reduced to 3 µg/L tPAH50 for HEWAFs and < 1.0 µg/L tPAH50 for thin oil sheens. Environmental conditions at the time of an oil spill will significantly influence oil toxicity and organismal response and should be taken into consideration in toxicity testing and oil spill damage assessments.

Acute Polychlorinated Biphenyl Benthic Invertebrate Toxicity Testing to Support the 2017 Chronic Dose-Response Sediment Injury Model.

As managers and decision makers evaluate pollutant risk, it is critical that we are able to measure an assessment of the injury. Often, these estimates are difficult to determine for benthic organisms, so in 2017 a chronic polychlorinated biphenyl (PCB) sediment dose-response model to predict benthic invertebrate injury was proposed. Given both natural resource trustee and consultant questions following publication concerning that the aqueous chronic toxicity testing data used in the 2017 model development were primarily from the 1970s and 1980s, this follow-up short communication is meant to provide the user some additional data that are more recent. With the advances in analytical and quantitative environmental chemistry (i.e., better detection limits and congener separation), we chose to complete acute aquatic toxicity testing using 3 estuarine invertebrates and lethal endpoints (20 and 50% lethal concentrations). This acute testing was selected because chronic aquatic testing for PCBs outside of the data used in the 2017 study was not available to us. The aquatic results used in the present study were changed to sediment using equilibrium partitioning, as done in the 2017 chronic model, after using the same organic-carbon partition coefficient and total organic carbon for our equilibrium partitioning (EqP)-measured calculations. Based on these acute aquatic toxicity results and a general acute-to-chronic injury concentration ratio of approximately 10, we found that the 2017 model was valid and, hence, that a 1.0 µg/g chronic PCB sediment criterion is a reasonable estimation of potential benthic invertebrate injury. This was followed by spiked sediment tests where percent acute sediment injury was compared to the EqP-derived chronic value and the results from 2017; modest agreement is shown. Environ Toxicol Chem 2021;40:1188-1193. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.

Sentinels of synthetics - a comparison of phthalate exposure between common bottlenose dolphins (Tursiops truncatus) and human reference populations.

Phthalates are chemical esters used as additives in common consumer goods, such as plastics, household cleaners, and personal care products. Phthalates are not chemically bound to the items to which they are added and can easily leach into the surrounding environment. Anthropogenic drivers, such as coastal plastic pollution and wastewater runoff, increase the exposure potential for coastal marine fauna. Phthalate exposure in free-ranging bottlenose dolphins has been the focus of recent study, with indications of heightened exposure to certain phthalate compounds. The objective of this study was to compare urinary phthalate metabolite concentrations among bottlenose dolphins (Tursiops truncatus) sampled in Sarasota Bay, FL, to levels reported in human samples collected as part of the Centers for Disease Control and Prevention's (CDC) National Health and Nutrition Examination Survey (NHANES). Monoethyl phthalate (MEP) and mono-(2-ethylhexyl) phthalate (MEHP) were the most prevalent metabolites detected in dolphin urine (n = 51; MEP = 29.41%; MEHP = 54.90%). The geometric mean (GM) concentration of MEP was significantly lower for dolphins (GM = 4.51 ng/mL; 95% CI: 2.77-7.34 ng/mL) compared to humans (p<0.05), while dolphin concentrations of MEHP (GM = 4.57 ng/mL; 95% CI: 2.37-8.80 ng/mL) were significantly higher than levels reported in NHANES (p<0.05). Health impacts to bottlenose dolphins resulting from elevated exposure to the MEHP parent compound (diethyl-2-ethylhexyl phthalate, DEHP) are currently unknown. However, given the evidence of endocrine disruption, reproductive impairment, and abnormal development in humans, pursuing investigations of potential health effects in exposed bottlenose dolphins would be warranted.

Effect of Louisiana sweet crude oil on a Pacific coral, Pocillopora damicornis.

Recent oil spill responses such as the Deepwater Horizon event have underscored the need for crude oil ecotoxicological threshold data for shallow water corals to assist in natural resource damage assessments. We determined the toxicity of a mechanically agitated oil-seawater mixture (high-energy water-accommodated fraction, HEWAF) of a sweet crude oil on a branched stony coral, Pocillopora damicornis. We report the results of two experiments: a 96 h static renewal exposure experiment and a "pulse-chase" experiment of three short-term exposure durations followed by a recovery period in artificial seawater. Five endpoints were used to determine ecotoxicological values: 1) algal symbiont chlorophyll fluorescence, 2) a tissue regeneration assay and a visual health metric with three endpoints: 3) tissue integrity, 4) tissue color, and 5) polyp behavior. The sum of 50 entrained polycyclic aromatic hydrocarbons (tPAH50) was used as a proxy for oil exposure. For the 96 h exposure dose response experiment, dark-adapted maximum quantum yield (Fv/Fm) of the dinoflagellate symbionts was least affected by crude oil (EC50 = 913 µg/L tPAH50); light-adapted effective quantum yield (EQY) was more sensitive (EC50 =  428 µg/L tPAH50). In the health assessment, polyp behavior (EC50 = 27 µg/L tPAH50) was more sensitive than tissue integrity (EC50 = 806 µg/L tPAH50) or tissue color (EC50 = 926 µg/L tPAH50). Tissue regeneration proved to be a particularly sensitive measurement for toxicity effects (EC50 = 10 µg/L tPAH50). Short duration (6-24 h) exposures using 503 µg/L tPAH50 (average concentration) resulted in negative impacts to P. damicornis and its symbionts. Recovery of chlorophyll a fluorescence levels for 6-24 h oil exposures was observed in a few hours (Fv/Fm) to several days (EQY) following recovery in fresh seawater. The coral health assessments for tissue integrity and tissue color were not affected following short-term oil exposure durations, but the 96 h treatment duration resulted in significant decreases for both. A reduction in polyp behavior (extension) was observed for all treatment durations, with recovery observed for the short-term (6-24 h) exposures within 1-2 days following placement in fresh seawater. Wounded and intact fragments exposed to oil treatments were particularly sensitive, with significant delays observed in tissue regeneration. Estimating ecotoxicological values for P. damicornis exposed to crude oil HEWAFs provides a basis for natural resource damage assessments for oil spills in reef ecosystems. These data, when combined with ecotoxicological values for other coral reef species, will contribute to the development of species sensitivity models.

Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cells: Preclinical Efficacy and Safety in Cervical Spinal Cord Injury.

Cervical spinal cord injury (SCI) remains an important research focus for regenerative medicine given the potential for severe functional deficits and the current lack of treatment options to augment neurological recovery. We recently reported the preclinical safety data of a human embryonic cell-derived oligodendrocyte progenitor cell (OPC) therapy that supported initiation of a phase I clinical trial for patients with sensorimotor complete thoracic SCI. To support the clinical use of this OPC therapy for cervical injuries, we conducted preclinical efficacy and safety testing of the OPCs in a nude rat model of cervical SCI. Using the automated TreadScan system to track motor behavioral recovery, we found that OPCs significantly improved locomotor performance when administered directly into the cervical spinal cord 1 week after injury, and that this functional improvement was associated with reduced parenchymal cavitation and increased sparing of myelinated axons within the injury site. Based on large scale biodistribution and toxicology studies, we show that OPC migration is limited to the spinal cord and brainstem and did not cause any adverse clinical observations, toxicities, allodynia, or tumors. In combination with previously published efficacy and safety data, the results presented here supported initiation of a phase I/IIa clinical trial in the U.S. for patients with sensorimotor complete cervical SCI. Stem Cells Translational Medicine 2017;6:1917-1929.

Immune responses and long-term disease recurrence status after telomerase-based dendritic cell immunotherapy in patients with acute myeloid leukemia.

BACKGROUND: Telomerase activity in leukemic blasts frequently is increased among patients with high-risk acute myeloid leukemia (AML). In the current study, the authors evaluated the feasibility, safety, immunogenicity, and therapeutic potential of human telomerase reverse transcriptase (hTERT)-expressing autologous dendritic cells (hTERT-DCs) in adult patients with AML. METHODS: hTERT-DCs were produced from patient-specific leukapheresis, electroporated with an mRNA-encoding hTERT and a lysosomal-targeting sequence, and cryopreserved. A total of 22 patients with a median age of 58 years (range, 30-75 years) with intermediate-risk or high-risk AML in first or second complete remission (CR) were enrolled. hTERT-DCs were generated for 24 patients (73%). A median of 17 intradermal vaccinations (range, 6-32 intradermal vaccinations) containing 1×107 cells were administered as 6 weekly injections followed by 6 biweekly injections. A total of 21 patients (16 in first CR, 3 in second CR, and 2 with early disease recurrence) received hTERT-DCs. RESULTS: hTERT-DCs were well tolerated with no severe toxicities reported, with the exception of 1 patient who developed idiopathic thrombocytopenic purpura. Of the 19 patients receiving hTERT-DCs in CR, 11 patients (58%) developed hTERT-specific T-cell responses that primarily were targeted toward hTERT peptides with predicted low human leukocyte antigen (HLA)-binding affinities. With a median follow-up of 52 months, 58% of patients in CR (11 of 19 patients) were free of disease recurrence at the time of their last follow-up visit; 57% of the patients who were aged ≥60 years (4 of 7 patients) also were found to be free of disease recurrence at a median follow-up of 54 months. CONCLUSIONS: The generation of hTERT-DCs is feasible and vaccination with hTERT-DCs appears to be safe and may be associated with favorable recurrence-free survival. Cancer 2017;123:3061-72. © 2017 American Cancer Society.

Baseline monitoring of organic sunscreen compounds along South Carolina's coastal marine environment.

Organic ultraviolet filters (UV-F) are increasingly being used in personal care products to protect skin and other products from the damaging effects of UV radiation. In this study, marine water was collected monthly for approximately one year from six coastal South Carolina, USA sites and analyzed for the occurrence of seven organic chemicals used as UV filters (avobenzone, dioxybenzone, octocrylene, octinoxate, oxybenzone, padimate-o and sulisobenzone). The results were used to examine the relationship between beach use and the distribution of UV-F compounds along coastal South Carolina, USA. Five of the seven target analytes were detected in seawater along coastal South Carolina during this study. Dioxybenzone and sulisobenzone were not detected. The highest concentrations measured were >3700 ng octocrylene/L and ~2200 ng oxybenzone/L and beach use was greatest at this site; a local beach front park. Patterns in concentrations were assessed based on season and a measure of beach use.

A survey of trace element distribution in tissues of the dwarf sperm whale (Kogia sima) stranded along the South Carolina coast from 1990-2011.

Few studies report trace elements in dwarf sperm whale (Kogia sima). As high trophic level predators, marine mammals are exposed through diet to environmental contaminants including metals from anthropogenic sources. Inputs of Hg, Pb, and Cd are of particular concern due to toxicity and potential for atmospheric dispersion and subsequent biomagnification. Liver and kidney tissues of stranded K. sima from coastal South Carolina, USA, were analyzed for 22 trace elements. Age-related correlations with tissue concentrations were found for some metals. Mean molar ratio of Hg:Se varied with age with higher ratios found in adult males. Maximum concentrations of Cd and Hg in both tissues exceeded historical FDA levels of concern, but none exceeded the minimum 100µg/g Hg threshold for hepatic damage. Tissue concentrations of some metals associated with contamination were low, suggesting that anthropogenic input may not be a significant source of some metals for these pelagic marine mammals.

Development of Species-Specific Ah Receptor-Responsive Third Generation CALUX Cell Lines with Enhanced Responsiveness and Improved Detection Limits.

The Ah receptor (AhR)-responsive CALUX (chemically activated luciferase expression) cell bioassay is commonly used for rapid screening of samples for the presence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin), dioxin-like compounds, and AhR agonists/antagonists. By increasing the number of AhR DNA recognition sites (dioxin responsive elements), we previously generated a novel third generation (G3) recombinant AhR-responsive mouse CALUX cell line (H1L7.5c3) with a significantly enhanced response to DLCs compared to existing AhR-CALUX cell bioassays. However, the elevated background luciferase activity of these cells and the absence of comparable G3 cell lines derived from other species have limited their utility for screening purposes. Here, we describe the development and characterization of species-specific G3 recombinant AhR-responsive CALUX cell lines (rat, human, and guinea pig) that exhibit significantly improved limit of detection and dramatically increased TCDD induction response. The low background luciferase activity, low minimal detection limit (0.1 pM TCDD) and enhanced induction response of the rat G3 cell line (H4L7.5c2) over the H1L7.5c3 mouse G3 cells, identifies them as a more optimal cell line for screening purposes. The utility of the new G3 CALUX cell lines were demonstrated by screening sediment extracts and a small chemical compound library for the presence of AhR agonists. The improved limit of detection and increased response of these new G3 CALUX cell lines will facilitate species-specific analysis of DLCs and AhR agonists in samples with low levels of contamination and/or in small sample volumes.

Preclinical safety of human embryonic stem cell-derived oligodendrocyte progenitors supporting clinical trials in spinal cord injury.

AIM: To characterize the preclinical safety profile of a human embryonic stem cell-derived oligodendrocyte progenitor cell therapy product (AST-OPC1) in support of its use as a treatment for spinal cord injury (SCI). MATERIALS & METHODS: The phenotype and functional capacity of AST-OPC1 was characterized in vitro and in vivo. Safety and toxicology of AST-OPC1 administration was assessed in rodent models of thoracic SCI. RESULTS: These results identify AST-OPC1 as an early-stage oligodendrocyte progenitor population capable of promoting neurite outgrowth in vitro and myelination in vivo. AST-OPC1 administration did not cause any adverse clinical observations, toxicities, allodynia or tumors. CONCLUSION: These results supported initiation of a Phase I clinical trial in patients with sensorimotor complete thoracic SCI.

An integrated assessment of habitat quality of national estuarine research reserves in the southeastern United States.

Multiple indicators of water quality, sediment quality, and biological condition were used to assess the status of ecological condition of National Estuarine Research Reserve System (NERRS) sites in North Carolina, South Carolina, and Georgia relative to a suite of corresponding scoring criteria. All measurements were made in subtidal aquatic habitats. Calculated scores were integrated into an overall index of habitat quality and used to make comparisons among the various NERR and nonNERR estuaries throughout the region. Sediment quality scores varied considerably among NERR sites, but in most cases were similar between individual NERR and non-NERR sites in corresponding states. Water quality and biological condition indicators scored consistently higher for NERRs versus non-NERR sites. Overall habitat quality scores also were consistently higher for NERRS sites, suggesting that these areas are on par with if not in slightly better condition ecologically than neighboring nonNERR estuaries. Portions of individual NERR sites rated as poor with respect to overall habitat quality were limited to relatively small areas (<13% of a reserve's total sampling area).

The relationship between land use and emerging and legacy contaminants in an Apex predator, the bottlenose dolphin (Tursiops truncatus), from two adjacent estuarine watersheds.

BACKGROUND: Persistent organohalogen contaminant (POC) exposure is of concern in marine mammals due to the potential for adverse health effects. Studies have examined POCs in marine mammals on a regional scale; however, limited data exists on POC concentrations relative to land use and watersheds. OBJECTIVE: Examine geographical variation of POC concentrations in bottlenose dolphins as it relates to land, and watershed, use. METHODS: POC (PCBs, DDTs, and PBDEs) concentrations were measured in blubber of bottlenose dolphins (n= 40) sampled in estuarine waters near Charleston, SC. Photo-identification sighting histories were used to assess the dolphins' use of estuarine waters in two adjacent watersheds (Cooper Subbasin and Stono Subbasin) in the study area and to determine land use (developed, forested, agriculture, and wetland) associations. RESULTS: Dolphins with ≥ 75% of their sightings in the Cooper Subbasin, which is characterized by a higher degree of developed land use, exhibited higher levels of PCBs, PBDEs, and total pesticides than those with ≥ 75% of their sightings in the Stono Subbasin. Observed differences were significant for ΣPBDEs and ΣDDTs/ΣPCBs ratio. Significant positive correlations were observed between ΣPBDEs and developed land use and between ΣDDTs/ΣPCBs and wetland land use. A significant negative correlation was observed between ΣDDTs/ΣPCBs and developed land use. CONCLUSION: The spatial pattern of PBDEs and the ΣDDTs/ΣPCBs detected in dolphin blubber was shown to vary significantly with adjacent watersheds and land use associations.

Using procedural blanks to generate analyte-specific limits of detection for persistent organic pollutants based on GC-MS analysis.

Several methods are used to generate a limit of detection for organic pollutants measured by gas chromatography-mass spectroscopy (GC-MS); all have theoretical and practical drawbacks. The current project investigated two common existing methods (statistical and empirical) for applicability to chromatographic properties from real samples, comparing these with a new proposed method using procedural blanks to estimate a minimum detectable peak area. Weaknesses of all three methods are discussed. The proposed method was superior to other examined methods in that it provided analyte-specific limits of detection linked to the recovery of mass-labeled internal standards for every analyte within every sample. Other identified quality assurance benefits included the following: enhanced protection against false positives; providing a sensitivity performance metric across batch, analyst, and instrument; enabling chemists with discretionary decisions specific to every analyte regarding detectability and interferences; and some strengths of both statistical and empirical techniques without major drawbacks of either. In marine sediment samples, the proposed method of calculating the limit of detection increased reporting of trace level (low- to subppb) GC-MS data for polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides (OCPs), and polycyclic aromatic hydrocarbons (PAHs) by up to 400% compared with the statistical method.

Antifouling biocides in water and sediments from California marinas.

Irgarol 1051 is a common antifouling biocide and is highly toxic to non-target plant species at low ng/L concentrations. We measured up to 254 ng/L Irgarol in water and up to 9 ng/g dry weight Irgarol in sediments from Southern California recreational marinas. Irgarol's metabolite, M1, concentrations were up to 62 ng/L in water and 5 ng/g dry weight in sediments. Another antifouling biocide, diuron, reached up to 68 ng/L in water and 4 ng/g dry weight in sediments. The maximum Irgarol concentrations in water were greater than the Irgarol concentration recommended as the plant toxicity benchmark (136 ng/L), suggesting that Irgarol concentrations may be high enough to cause changes in phytoplankton communities in the sampled marinas. Irgarol concentrations measured in sediments were greater than calculated Environmental Risk Limits (ERLs) for Irgarol in sediments (1.4 ng/g). Antifouling pesticide accumulation in sediments may present a potential undetermined risk for benthic organisms.