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Biomedical subjects

John R Dunn

Publications and source records attributed to John R Dunn.

8 recordsLinked to original sources

Shiga-toxigenic Escherichia coli O157 in agricultural fair livestock, United States.

Agricultural fairs exhibiting livestock are increasingly implicated in human Shiga-toxigenic Escherichia coli O157:H7 (STEC O157:H7) outbreaks. To estimate livestock STEC O157:H7 prevalence at US fairs, we collected 2,919 fecal specimens at 29 county fairs in 2 states and at 3 state fairs in 2002. Fly pools were also collected. STEC O157:H7 was isolated from livestock at 31 (96.9%) of 32 fairs, including 11.4% of 1,407 cattle, 1.2% of 1,102 swine, 3.6% of 364 sheep and goats, and 5.2% of 154 fly pools. Cattle, swine, and flies at some fairs shared indistinguishable STEC O157:H7 isolate subtypes. In 2003, a total of 689 ambient environmental samples were collected at 20 fairgrounds 10-11 months after 2002 livestock sampling while fairgrounds were livestock-free. Four beef barn environmental samples at 3 fairgrounds yielded STEC O157:H7. These data suggest that STEC O157 is common and transmissible among livestock displayed at agricultural fairs and persists in the environment after the fair.

Animals↗

Determining the error of dose estimates and minimum and maximum acceptable concentrations from assays with nonlinear dose-response curves.

A method is described here that uses a modified Monte-Carlo method to provide an improved estimate of the confidence bounds of concentration estimates. This method accommodates even strongly nonlinear curve models, such as the five parameter logistic model, in contrast to the common but often poor approach of linearizing the regression problem and using linear theory to obtain the confidence bounds. The method uses an interpolation technique to reduce artifacts in the precision profile due to small simulation sample sizes and proximity to horizontal asymptotes in the curve model. The paper also describes how to define and calculate the minimum and maximum acceptable concentrations of dose-response curves by locating the concentrations where the size of the error, defined in terms of the size of the concentration confidence interval, exceeds the threshold of acceptability determined for the application.

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The five-parameter logistic: a characterization and comparison with the four-parameter logistic.

Improvements in assay technology have reduced the amount of random variation in measured responses to the point where even slight asymmetry of the assay data can be more significant than random variation. Use of the five-parameter logistic (5PL) function to fit dose-response data easily accommodates such asymmetry. The 5PL can dramatically improve the accuracy of asymmetric assays over the use of symmetric models such as the four-parameter logistic (4PL) function. Until recently, however, the process of fitting the 5PL function has been difficult, with the result that the 4PL function has continued to be used even for highly asymmetric data. Various ad hoc modifications of the 4PL method have been developed in an attempt to address asymmetric data. However, recent advances in numerical methods and assay analysis software have rendered easier the fitting of the 5PL routine. This paper demonstrates how use of the 5PL function can improve assay performance over the 4PL and its variants. Specifically, the improvement in the accuracy of concentration estimates that can be obtained using the 5PL over the 4PL as a function of the asymmetry present in the data is studied. The behavior of the 5PL curve and how it differs from the 4PL curve are discussed. Common experimental designs, which can lead to ill-conditioned regression problems, are also examined.

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Effects of positive results for Mycobacterium avium subsp paratuberculosis as determined by microbial culture of feces or antibody ELISA on results of caudal fold tuberculin test and interferon-gamma assay for tuberculosis in cattle.

OBJECTIVE: To determine whether cattle testing positive for Mycobacterium avium subsp paratuberculosis as determined by microbial culture of feces or antibody ELISA were more likely to have false-positive responses on the caudal fold tuberculin (CFT) test or interferon-gamma (IFN-gamma) assay for Mycobacterium bovis than cattle testing negative for M paratuberculosis. ANIMALS: 1043 cattle from 10 herds in Michigan. PROCEDURE: Feces and blood samples for plasma were collected from cattle > or =24 months old on the day the CFT test was read. Fecal samples were submitted for microbial culture for M paratuberculosis. Plasma samples were tested for antibody against M paratuberculosis, and IFN-gamma after stimulation with purified protein derivative tuberculin from M bovis or M avium. RESULTS: Of 1043 cattle, 180 (17.3%) had positive CFT test results (suspects) and 8 (0.8%) had positive IFN-gamma assay results after stimulation with purified protein derivative tuberculin from M bovis. Forty-five (4.3%) and 115 (11.0%) cattle tested positive for M paratuberculosis as determined by microbial culture of feces and antibody ELISA, respectively. Cattle with positive responses for M paratuberculosis appeared to have an increased likelihood of false-positive results on the CFT test, although this association was not significant. CONCLUSIONS AND CLINICAL RELEVANCE: No significant association was detected among cattle testing positive for M paratuberculosis as determined by microbial culture of feces and antibody ELISA and positive CFT test and IFN-gamma assay results for M bovis.

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Measuring parallelism, linearity, and relative potency in bioassay and immunoassay data.

There is often a need to determine parallelism or linearity between pairs of dose-response data sets for various biological applications. This article describes a technique based on a modification of the well-known extra-sum-of-squares principle of statistical regression. The standard extra-sum-of-squares method uses an F-distributed ratio as a statistic and an F-test based on this statistic as the parallelism test. It is shown here that this metric does not directly measure the parallelism between the two curves and can often vary in opposition to actual parallelism. To overcome this problem, a metric based on a chi-square test applied directly on the chi-square-distributed extra-sum-of-squares statistic is developed, which is shown to correspond directly to parallelism. This parallelism metric does not suffer from the shortcomings of the conventional F-test-based metric, and is a more reliable and appropriate measure of parallelism. The article also shows that the choice of curve model has a large effect on the sensitivity of either metric, and that using an asymmetric model, such as the asymmetric five-parameter logistic function, a generalization of the commonly used symmetric four-parameter logistic function, is necessary when working with asymmetric dose-response data. The effect of noise, as well as the importance of correct weighting on the parallelism metrics and the relative potency, is also studied.

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Prevalence of Shiga-toxigenic Escherichia coli O157:H7 in adult dairy cattle.

OBJECTIVE: To describe shiga-toxigenic Escherichia coil O157:H7 (STEC O157:H7) fecal shedding prevalence, seasonal fecal shedding patterns, and site-specific prevalence from the oral cavity, skin, and feces of dairy cattle. DESIGN: Cross-sectional study. ANIMALS: Adult dairy cattle from 13 herds in Louisiana. PROCEDURE: Samples were cultured for STEC O157 by use of sensitive and specific techniques, including selective broth enrichment, immunomagnetic separation, monoclonal antibody-based O:H enzyme immunoassay serotyping, and polymerase chain reaction virulence gene characterization. Point estimates and 95% confidence intervals were calculated for fecal shedding prevalence as well as site-specific prevalence from the oral cavity, skin, and feces. Logistic regression was used to assess seasonal variation and differences at various stages of lactation with respect to fecal shedding of STEC O157 in cattle sampled longitudinally. RESULTS: Summer prevalence in herds in = 13) was 38.5%, with a cow-level prevalence of 6.5%. Among positive herds, prevalence ranged from 3% to 34.6%. Samples from 3 of 5 herds sampled quarterly over 1 year yielded positive results for STEC O157. In herds with STEC O157, an increase in cow-level prevalence was detected during spring (13.3%) and summer (10.5%), compared with values for fall and winter. Site-specific prevalences of STEC O157:H7 from oral cavity, skin, and fecal samples were 0%, 0.7%, and 25.2%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Our data indicated that STEC O157:H7 was commonly isolated from dairy cows in Louisiana, seasonally shed, and isolated from the skin surface but not the oral cavity of cows.

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Escherichia coli O157:H7 in a cohort of weaned, preconditioned range beef calves.

Escherichia coli O157:H7 (EC O157) is an important cause of foodborne disease. Cattle are reservoirs for the bacteria and are implicated in transmission to humans. Prevalence data in prefeedlot calves are limited. With the use of sensitive methods, a cohort of weaned beef calves (n = 408) was sampled before and after preconditioning to estimate fecal point prevalence and describe changes in EC O157 fecal shedding. EC O157 isolates were confirmed and characterized by PCR and pulsed-field gel electrophoresis. Calves from 29 cow-calf farms were commingled at three preconditioning sites and placed on a transition ration containing oxytetracycline (200 g/ton) for 45 days. Initial animal-level fecal point prevalence was 2.5% (95% confidence interval, 1 to 5) with a herd-level prevalence of 17.2% (95% confidence interval, 6 to 36). Point prevalence following the preconditioning feeding period was 0%. An unexpected finding in our study was EC O157 isolates that were Shiga toxin-deficient. Pulsed-field gel electrophoresis subtypes of EC O157 were unique in epidemiologically unlinked herds, except one herd that had two unique subtypes. We expected, but observed, neither increased fecal shedding in the cohort nor horizontal transmission of unique EC O157 subtypes. The absence of fecal shedding following the 45-day feeding period might be attributable to seasonal influences, inhibitory concentrations of oxytetracycline in the transition ration, or transient colonization that ended before sampling. EC O157 is apparently widely dispersed at low prevalence in U.S. prefeedlot, weaned calves.

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Prevalence of Escherichia coli O157:H7 in white-tailed deer from Louisiana.

Escherichia coli O157:H7 (EC O157) is an important zoonosis. White-tailed deer (Odocoileus virginianus) have been implicated in transmission of this bacterium to humans and have been suggested as reservoirs that might affect carriage in cattle populations. Our study objectives were to estimate prevalence of EC O157 in feces of hunter-harvested deer and to describe fecal shedding patterns in a captive herd sampled over 1 yr. Prevalence of EC O157 in hunter-harvested deer was 0.3% (n = 338). In August 2001, EC O157 was detected in one of 55 deer (1.8%) from the captive herd. Prevalence over the 1-yr period was 0.4% (n = 226). Escherichia coli O157:H7 was rarely isolated from hunter-harvested deer during the winter. We could not describe a seasonal shedding pattern based on one positive sample in the captive herd. These data do not support a prominent role of deer as a reservoir for EC O157 for cattle or humans.

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