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Other Publications (21)

Articles by Todd Campbell in JoVE

 JoVE Biology

Spatial Multiobjective Optimization of Agricultural Conservation Practices using a SWAT Model and an Evolutionary Algorithm

1School of Environmental and Forest Sciences, University of Washington, 2Center for Agricultural and Rural Development, Department of Economics, Iowa State University, 3Department of Civil, Architectural, and Environmental Engineering, North Carolina A&T University, 4Iowa Geological and Water Survey


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This work demonstrates an integration of a water quality model with an optimization component utilizing evolutionary algorithms to solve for optimal (lowest-cost) placement of agricultural conservation practices for a specified set of water quality improvement objectives. The solutions are generated using a multi-objective approach, allowing for explicit quantification of tradeoffs.

Other articles by Todd Campbell on PubMed

Divalproex Sodium (Depakote) for Alcohol Withdrawal and Relapse Prevention

This pilot study evaluates the safety and efficacy of divalproex sodium (Depakote) for alcohol withdrawal and relapse prevention. Sixteen patients in moderate alcohol withdrawal were randomized to receive a standard benzodiazepine detoxification, depakote detoxification, or depakote detox plus maintenance. Symptom reduction occurred more rapidly and consistently in the depakote treated patients than in the benzodiazepine control group, and at six-week follow up a greater percentage of patients in the depakote maintenance group were completely abstinent than either detox-only group. There were no significant differences in sociodemographic or drinking data amongst the three cohort samples at baseline. Our findings suggest that the anticonvulsant divalproex sodium (Depakote) may be a safe and efficacious alternative to benzodiazepines for the treatment of alcohol withdrawal. It may be an advantageous alternative for outpatient detoxification, as it has no abuse potential, pharmacologic synergy with alcohol, or substantial cognitive or psychomotor side effects.

Scalp Necrosis: an Unusual Presentation of Giant Cell Arteritis

A Logical Starting Point for Developing Priorities for Lizard and Snake Ecotoxicology: a Review of Available Data

Reptiles, specifically lizards and snakes, usually are excluded from environmental contamination studies and ecological risk assessments. This brief summary of available lizard and snake environmental contaminant data is presented to assist in the development of priorities for lizard and snake ecotoxicology. Most contaminant studies were not conducted recently, list animals found dead or dying after pesticide application, report residue concentrations after pesticide exposure, compare contaminant concentrations in animals from different areas, compare residue concentrations found in different tissues and organs, or compare changes in concentrations over time. The biological significance of the contaminant concentrations is rarely studied. A few recent studies, especially those conducted on modern pesticides, link the contaminant effects with exposure concentrations. Nondestructive sampling techniques for determining organic and inorganic contaminant concentrations in lizards and snakes recently have been developed. Studies that relate exposure, concentration, and effects of all types of environmental contaminants on lizards and snakes are needed. Because most lizards eat insects, studies on the exposure, effects, and accumulation of insecticides in lizards, and their predators, should be a top priority. Because all snakes are upper-trophic-level carnivores, studies on the accumulation and effects of contaminants that are known to bioaccumulate or biomagnify up the food chain should be the top priority.

Alcohol and Other Drug Abuse Counselors' Attitudes and Resources for Integrating Research and Practice

The state of Wisconsin recently launched a Research-to-Practice Initiative. One aspect of the Wisconsin initiative was to survey Wisconsin-Certified Alcohol and other Drug Abuse Counselors (CADCs) to assess their attitudes, reported practices, and resources in regard to the integration of research and practice. The sample for the present study included 366 CADCs. Of the 366 respondents, 62 percent (n = 226) were female and 38 percent (n = 140) were male. The respondents were primarily Caucasian (90 percent) with the remaining respondents identifying as African American (4 percent), Native American (2 percent), Hispanic (1 percent), and Asian American (0.5 percent). The results from the survey indicated that the majority of respondents have access to computers, e-mail, and the Internet at their workplace; report being "satisfied" or "very satisfied" with their education and training; and tend to approve of the efforts to integrate research and practice. Incentives, barriers and strategies to integrate research and practice are discussed.

Neuropsychological Functioning of Homeless Men

Numerous biological and psychological factors associated with impaired neurological functioning have been identified as common among the homeless, but there has been relatively little systematic examination of the cognitive functioning of homeless people. This study explored the neuropsychological functioning of 90 homeless men. There was great variability in their test scores, but the presence of possible cognitive impairment was detected in 80% of the sample. Average general intellectual functioning and reading abilities were found to be relatively low, and the incidence of impairments in reading, new verbal learning, memory, and attention and concentration was high. These findings suggest that the homeless men in this study had considerable assessment and treatment needs that were not being met by most of the health and social services offered to them.

Gender and Spatial Patterns in Metal Concentrations in Brown Anoles (Anolis Sagrei) in Southern Florida, USA

Comparatively little is known about heavy metal levels in reptiles, particularly for lizards. Yet lizards often are common predators that could serve as bioindicators of contamination on a small spatial scale. This study examined the differences in metal concentrations of adult brown anoles (Anolis sagrei) for arsenic, cadmium, chromium, lead, manganese, mercury, and selenium in six locations in southern Florida, USA, from Lake Okeechobee (Pahokee) south to Key West. We predicted that levels of contaminants would be higher in the industrialized ports (Port Everglades, Port of Miami) and at a landfill (in Key West) compared to a campground, tropical garden, and marine laboratory. Males were significantly larger than females, as expected. Although there were significant locational differences in metal concentrations, they did not fit a consistent pattern, either among sites or between reference and study sites. However, the lowest levels were generally found at Everglades Marina and Campground (except for selenium) and at Fairchild Tropical Garden (except for manganese). For females, size was significantly correlated with cadmium, lead, and mercury levels, while for males, there were significant correlations between length and arsenic, chromium, and manganese concentrations. Where there were gender differences in metal levels, females had significantly higher levels than males even though they were smaller. We attribute these gender differences to differences in diet due to microhabitat differences in foraging locations. Females spend more time feeding near the ground and males spend more time feeding on tree trunks and branches where they consume more flying insects. This is the first study that examines concentrations of metals in lizards in the United States, and suggests that nonnative lizards may be useful in toxicological studies.

Development of the Motivational Interviewing Supervision and Training Scale

The movement to use empirically supported treatments has increased the need for researchers and supervisors to evaluate therapists' adherence to and the quality with which they implement those interventions. Few empirically supported approaches exist for providing these types of evaluations. This is also true for motivational interviewing, an empirically supported intervention important in the addictions field. This study describes the development and psychometric evaluation of the Motivational Interviewing Supervision and Training Scale (MISTS), a measure intended for use in training and supervising therapists implementing motivational interviewing. Satisfactory interrater reliability was found (generalizability coefficient p(2) = .79), and evidence was found supporting the convergent and discriminant validity of the MISTS. Recommendations for refinement of the measure and future research are discussed.

Use of Central Stonerollers (Cyprinidae: Campostoma Anomalum) from Tennessee As a Bioindicator of Metal Contamination

We compared the levels of arsenic, cadmium, chromium, lead, manganese, mercury and selenium in a small species of fish (Central stonerollers, Campostoma anomalum) collected from East Fork Poplar Creek (EFPC) and a reference site in eastern Tennessee. Stonerollers are minnows in the Cyprinidae family that serve as prey for many carnivores in aquatic systems. Fish were collected from East Fork Poplar Creek within the U.S. Department of Energy's Y-12 National Security Complex, part of the Oak Ridge Reservation, and from a reference stretch of the Little River in East Tennessee. Whole fish were homogenized for analysis. Concentrations of all metals (except arsenic) were significantly higher in stonerollers from EFPC compared to the reference site. Mercury levels in minnows from EFPC averaged 0.4 ppm (microg/g), four times higher than the average for fish in the U.S. in general. This was higher than levels in fish from the nearby Clinch River and higher than fillets of white bass (Morone chrysops) from the same creek. Most metal levels were inversely related to size and weight of the stonerollers, perhaps due to growth dilution.

High-density Mapping and Comparative Analysis of Agronomically Important Traits on Wheat Chromosome 3A

Bread wheat chromosome 3A has been shown to contain genes/QTLs controlling grain yield and other agronomic traits. The objectives of this study were to generate high-density physical and genetic-linkage maps of wheat homoeologous group 3 chromosomes and reveal the physical locations of genes/QTLs controlling yield and its component traits, as well as agronomic traits, to obtain a precise estimate of recombination for the corresponding regions and to enrich the QTL-containing regions with markers. Physical mapping was accomplished by 179 DNA markers mostly representing expressed genes using 41 single-break deletion lines. Polymorphism survey of cultivars Cheyenne (CNN) and Wichita (WI), and a substitution line of CNN carrying chromosome 3A from WI [CNN(WI3A)], with 142 RFLP probes and 55 SSR markers revealed that the extent of polymorphism is different among various group 3 chromosomal regions as well as among the homoeologs. A genetic-linkage map for chromosome 3A was developed by mapping 17 QTLs for seven agronomic traits relative to 26 RFLP and 15 SSR chromosome 3A-specific markers on 95 single-chromosome recombinant inbred lines. Comparison of the physical maps with the 3A genetic-linkage map localized the QTLs to gene-containing regions and accounted for only about 36% of the chromosome. Two chromosomal regions containing 9 of the 17 QTLs encompassed less than 10% of chromosome 3A but accounted for almost all of the arm recombination. To identify rice chromosomal regions corresponding to the particular QTL-containing wheat regions, 650 physically mapped wheat group 3 sequences were compared with rice genomic sequences. At an E value of E < or = 10(-5), 82% of the wheat group 3 sequences identified rice homologs, of which 54% were on rice chromosome 1. The rice chromosome 1 region collinear with the two wheat regions that contained 9 QTLs was about 6.5 Mb.

Measures of Fidelity in Motivational Enhancement: a Systematic Review

The movement to use empirically supported treatments has increased the need for researchers and clinical supervisors to evaluate therapists' adherence to and competence in particular empirically supported interventions. Motivational interviewing (MI) is an empirically supported intervention for substance abuse and other behavioral problems. However, for this intervention to work, it must be provided with fidelity and skill. This article provides a systematic review of MI adherence and competence measures that have been developed and described independently elsewhere. Recommendations for refinement of the measures and future research are also discussed.

Metal Levels in Blood, Muscle and Liver of Water Snakes (Nerodia Spp.) from New Jersey, Tennessee and South Carolina

Reptiles, particularly snakes, could serve as bioindicators of contamination because some are comparatively long-lived, exhibit different trophic levels, and are at the top of their food chains. We test the null hypothesis that there are no differences in the concentrations of heavy metals in the blood, muscle and liver of water snakes (Nerodia spp.) from rivers in New Jersey, Tennessee and South Carolina. While the former site is in an urban/suburban area, the latter two sites are relatively rural and are located on Department of Energy sites. For the snakes from New Jersey, there were significant differences in metal concentrations among tissues for all metals, the highest levels for arsenic and selenium were in liver and kidney, for cadmium were in the liver, for chromium and lead were in skin, and for mercury and manganese were in the muscle. Body length was not correlated with metal levels, and there were more significant correlations for skin with internal tissues than for blood with other tissues. There were more significant correlations for mercury than for other metals. In comparing metal levels among states, levels were generally higher for snakes collected from South Carolina. These data indicate that, since water snakes accumulate contaminants differentially as a function of location, they can be useful bioindicators of environmental exposure to contaminants. Moreover, because of their wide geographical distribution and use of varying trophic compartments, this genus can be useful for cross-site comparisons.

Single-molecule Enzyme-linked Immunosorbent Assay Detects Serum Proteins at Subfemtomolar Concentrations

The ability to detect single protein molecules in blood could accelerate the discovery and use of more sensitive diagnostic biomarkers. To detect low-abundance proteins in blood, we captured them on microscopic beads decorated with specific antibodies and then labeled the immunocomplexes (one or zero labeled target protein molecules per bead) with an enzymatic reporter capable of generating a fluorescent product. After isolating the beads in 50-fl reaction chambers designed to hold only a single bead, we used fluorescence imaging to detect single protein molecules. Our single-molecule enzyme-linked immunosorbent assay (digital ELISA) approach detected as few as approximately 10-20 enzyme-labeled complexes in 100 microl of sample (approximately 10(-19) M) and routinely allowed detection of clinically relevant proteins in serum at concentrations (<10(-15) M) much lower than conventional ELISA. Digital ELISA detected prostate-specific antigen (PSA) in sera from patients who had undergone radical prostatectomy at concentrations as low as 14 fg/ml (0.4 fM).

Identification of the Family of Aquaporin Genes and Their Expression in Upland Cotton (Gossypium Hirsutum L.)

Cotton (Gossypium spp.) is produced in over 30 countries and represents the most important natural fiber in the world. One of the primary factors affecting both the quantity and quality of cotton production is water. A major facilitator of water movement through cell membranes of cotton and other plants are the aquaporin proteins. Aquaporin proteins are present as diverse forms in plants, where they function as transport systems for water and other small molecules. The plant aquaporins belong to the large major intrinsic protein (MIP) family. In higher plants, they consist of five subfamilies including plasma membrane intrinsic proteins (PIP), tonoplast intrinsic proteins (TIP), NOD26-like intrinsic proteins (NIP), small basic intrinsic proteins (SIP), and the recently discovered X intrinsic proteins (XIP). Although a great deal is known about aquaporins in plants, very little is known in cotton.

Bayesian Mixture Structural Equation Modelling in Multiple-trait QTL Mapping

Quantitative trait loci (QTLs) mapping often results in data on a number of traits that have well-established causal relationships. Many multi-trait QTL mapping methods that account for correlation among the multiple traits have been developed to improve the statistical power and the precision of QTL parameter estimation. However, none of these methods are capable of incorporating the causal structure among the traits. Consequently, genetic functions of the QTL may not be fully understood. In this paper, we developed a Bayesian multiple QTL mapping method for causally related traits using a mixture structural equation model (SEM), which allows researchers to decompose QTL effects into direct, indirect and total effects. Parameters are estimated based on their marginal posterior distribution. The posterior distributions of parameters are estimated using Markov Chain Monte Carlo methods such as the Gibbs sampler and the Metropolis-Hasting algorithm. The number of QTLs affecting traits is determined by the Bayes factor. The performance of the proposed method is evaluated by simulation study and applied to data from a wheat experiment. Compared with single trait Bayesian analysis, our proposed method not only improved the statistical power of QTL detection, accuracy and precision of parameter estimates but also provided important insight into how genes regulate traits directly and indirectly by fitting a more biologically sensible model.

Least-cost Control of Agricultural Nutrient Contributions to the Gulf of Mexico Hypoxic Zone

In 2008, the hypoxic zone in the Gulf of Mexico, measuring 20 720 km2, was one of the two largest reported since measurement of the zone began in 1985. The extent of the hypoxic zone is related to nitrogen and phosphorous loadings originating on agricultural fields in the upper Midwest. This study combines the tools of evolutionary computation with a water quality model and cost data to develop a trade-off frontier for the Upper Mississippi River Basin specifying the least cost of achieving nutrient reductions and the location of the agricultural conservation practices needed. The frontier allows policymakers and stakeholders to explicitly see the trade-offs between cost and nutrient reductions. For example, the cost of reducing annual nitrate-N loadings by 30% is estimated to be US$1.4 billion/year, with a concomitant 36% reduction in P and the cost of reducing annual P loadings by 30% is estimated to be US$370 million/year, with a concomitant 9% reduction in nitrate-N.

Regression-based Multi-trait QTL Mapping Using a Structural Equation Model

Quantitative trait loci (QTL) mapping often results in data on a number of traits that have well-established causal relationships. Many multi-trait QTL mapping methods that account for the correlation among multiple traits have been developed to improve the statistical power and the precision of QTL parameter estimation. However, none of these methods are capable of incorporating the causal structure among the traits. Consequently, genetic functions of the QTL may not be fully understood. Structural equation modeling (SEM) allows researchers to explicitly characterize the causal structure among the variables and to decompose effects into direct, indirect, and total effects. In this paper, we developed a multi-trait SEM method of QTL mapping that takes into account the causal relationships among traits related to grain yield. Performance of the proposed method is evaluated by simulation study and applied to data from a wheat experiment. Compared with single trait analysis and the multi-trait least-squares analysis, our multi-trait SEM improves statistical power of QTL detection and provides important insight into how QTLs regulate traits by investigating the direct, indirect, and total QTL effects. The approach also helps build biological models that more realistically reflect the complex relationships among QTL and traits and is more precise and efficient in QTL mapping than single trait analysis.

Simultaneous Detection of Single Molecules and Singulated Ensembles of Molecules Enables Immunoassays with Broad Dynamic Range

We report a method for combining the detection of single molecules (digital) and an ensemble of molecules (analog) that is capable of detecting enzyme label from 10(-19) M to 10(-13) M, for use in high sensitivity enzyme-linked immunosorbent assays (ELISA). The approach works by capturing proteins on microscopic beads, labeling the proteins with enzymes using a conventional multistep immunosandwich approach, isolating the beads in an array of 50-femtoliter wells (Single Molecule Array, SiMoA), and detecting bead-associated enzymatic activity using fluorescence imaging. At low concentrations of proteins, when the ratio of enzyme labels to beads is less than ∼1.2, beads carry either zero or low numbers of enzymes, and protein concentration is quantified by counting the presence of "on" or "off" beads (digital regime). (1) At higher protein concentrations, each bead typically carries multiple enzyme labels, and the average number of enzyme labels present on each bead is quantified from a measure of the average fluorescence intensity (analog regime). Both the digital and analog concentration ranges are quantified by a common unit, namely, average number of enzyme labels per bead (AEB). By combining digital and analog detection of singulated beads, a linear dynamic range of over 6 orders of magnitude to enzyme label was achieved. Using this approach, an immunoassay for prostate specific antigen (PSA) was developed. The combined digital and analog PSA assay provided linear response over approximately four logs of concentration ([PSA] from 8 fg/mL to 100 pg/mL or 250 aM to 3.3 pM). This approach extends the dynamic range of ELISA from picomolar levels down to subfemtomolar levels in a single measurement.

Single Molecule Measurements of Tumor Necrosis Factor α and Interleukin-6 in the Plasma of Patients with Crohn's Disease

The quantitative measurement of inflammatory cytokines in blood has been limited by insufficient sensitivity of conventional immunoassays. This limitation has prevented the widespread clinical monitoring of cytokine concentrations in chronic inflammatory diseases. We applied a sensitive, single molecule detection technology to measure TNF-α and IL-6 in the plasma of patients with Crohn's disease (CD), before and after treatment with anti-TNF-α therapy. Plasma from 17 patients with CD was collected prior to initiation of anti-TNF-α therapy, and the Crohn's disease activity index (CDAI) was determined for each patient. A sub-set of these patients returned for follow up 12 weeks after treatment started. Plasma from age- and gender-matched controls was also collected. Digital ELISAs were developed for TNF-α and IL-6, and the plasma concentrations of these cytokines were determined using digital ELISA. The limits of detection of the TNF-α and IL-6 digital ELISAs were 0.008 pg/mL and 0.006 pg/mL, respectively. Both cytokines were detected in all samples using digital ELISA and the concentrations of TNF-α and IL-6 in the plasma of patients with CD were (3.6±0.9) pg/mL and (10.9±11.2) pg/mL, respectively. TNF-α levels in patients and healthy controls were not significantly different, but the IL-6 levels in plasma were significantly elevated in patients compared to controls. After therapy, the mean reduction of the concentrations of free TNF-α and IL-6 were 46% and 58%, respectively. Digital ELISA provided the first quantitative measurements of TNF-α and IL-6 concentrations in the plasma of all patients in a population with CD. The changes in cytokine concentrations after therapy--which could be quantified because of the high sensitivity of digital ELISA--could be used for monitoring therapeutic efficacy.

Hypoxia Due to Cardiac Arrest Induces a Time-dependent Increase in Serum Amyloid β Levels in Humans

Amyloid β (Aβ) peptides are proteolytic products from amyloid precursor protein (APP) and are thought to play a role in Alzheimer disease (AD) pathogenesis. While much is known about molecular mechanisms underlying cerebral Aβ accumulation in familial AD, less is known about the cause(s) of brain amyloidosis in sporadic disease. Animal and postmortem studies suggest that Aβ secretion can be up-regulated in response to hypoxia. We employed a new technology (Single Molecule Arrays, SiMoA) capable of ultrasensitive protein measurements and developed a novel assay to look for changes in serum Aβ42 concentration in 25 resuscitated patients with severe hypoxia due to cardiac arrest. After a lag period of 10 or more hours, very clear serum Aβ42 elevations were observed in all patients. Elevations ranged from approximately 80% to over 70-fold, with most elevations in the range of 3-10-fold (average approximately 7-fold). The magnitude of the increase correlated with clinical outcome. These data provide the first direct evidence in living humans that ischemia acutely increases Aβ levels in blood. The results point to the possibility that hypoxia may play a role in the amyloidogenic process of AD.

Isolation and Detection of Single Molecules on Paramagnetic Beads Using Sequential Fluid Flows in Microfabricated Polymer Array Assemblies

We report a method for isolating individual paramagnetic beads in arrays of femtolitre-sized wells and detecting single enzyme-labeled proteins on these beads using sequential fluid flows in microfabricated polymer array assemblies. Arrays of femtolitre-sized wells were fabricated in cyclic olefin polymer (COP) using injection moulding based on DVD manufacturing. These arrays were bonded to a complementary fluidic structure that was also moulded in COP to create an enclosed device to allow delivery of liquids to the arrays. Enzyme-associated, paramagnetic beads suspended in aqueous solutions of enzyme substrate were delivered fluidically to the array such that one bead per well was loaded by gravity. A fluorocarbon oil was then flowed into the device to remove excess beads from the surface of the array, and to seal and isolate the femtolitre-sized wells containing beads and enzyme substrate. The device was then imaged using standard fluorescence imaging to determine which wells contained single enzyme molecules. The analytical performance of this device as the detector for digital ELISA compared favourably to the standard method, i.e., glass arrays mechanically sealed against a silicone gasket; prostate specific antigen (PSA) could be detected from 0.011 pg mL(-1) up to 100 pg mL(-1). The use of an enclosed fluidic device to isolate beads in single-molecule arrays offers a multitude of advantages for low-cost manufacturing, ease of automation, and instrument development to enable applications in biomarker validation and medical diagnosis.

Genome-wide Identification of Differentially Expressed Genes Under Water Deficit Stress in Upland Cotton (Gossypium Hirsutum L.)

Cotton is the world's primary fiber crop and is a major agricultural commodity in over 30 countries. Like many other global commodities, sustainable cotton production is challenged by restricted natural resources. In response to the anticipated increase of agricultural water demand, a major research direction involves developing crops that use less water or that use water more efficiently. In this study, our objective was to identify differentially expressed genes in response to water deficit stress in cotton. A global expression analysis using cDNA-Amplified Fragment Length Polymorphism was conducted to compare root and leaf gene expression profiles from a putative drought resistant cotton cultivar grown under water deficit stressed and well watered field conditions.

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