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Tom Burr

Publications and source records attributed to Tom Burr.

9 recordsLinked to original sources
PubMed2007

Computer-aided diagnosis with potential application to rapid detection of disease outbreaks.

Our objectives are to quickly interpret symptoms of emergency patients to identify likely syndromes and to improve population-wide disease outbreak detection. We constructed a database of 248 syndromes, each syndrome having an estimated probability of producing any of 85 symptoms, with some two-way, three-way, and five-way probabilities reflecting correlations among symptoms. Using these multi-way probabilities in conjunction with an iterative proportional fitting algorithm allows estimation of full conditional probabilities. Combining these conditional probabilities with misdiagnosis error rates and incidence rates via Bayes theorem, the probability of each syndrome is estimated. We tested a prototype of computer-aided differential diagnosis (CADDY) on simulated data and on more than 100 real cases, including West Nile Virus, Q fever, SARS, anthrax, plague, tularaemia and toxic shock cases. We conclude that: (1) it is important to determine whether the unrecorded positive status of a symptom means that the status is negative or that the status is unknown; (2) inclusion of misdiagnosis error rates produces more realistic results; (3) the naive Bayes classifier, which assumes all symptoms behave independently, is slightly outperformed by CADDY, which includes available multi-symptom information on correlations; as more information regarding symptom correlations becomes available, the advantage of CADDY over the naive Bayes classifier should increase; (4) overlooking low-probability, high-consequence events is less likely if the standard output summary is augmented with a list of rare syndromes that are consistent with observed symptoms, and (5) accumulating patient-level probabilities across a larger population can aid in biosurveillance for disease outbreaks.

Algorithms↗
PubMed2006

Accounting for seasonal patterns in syndromic surveillance data for outbreak detection.

BACKGROUND: Syndromic surveillance (SS) can potentially contribute to outbreak detection capability by providing timely, novel data sources. One SS challenge is that some syndrome counts vary with season in a manner that is not identical from year to year. Our goal is to evaluate the impact of inconsistent seasonal effects on performance assessments (false and true positive rates) in the context of detecting anomalous counts in data that exhibit seasonal variation. METHODS: To evaluate the impact of inconsistent seasonal effects, we injected synthetic outbreaks into real data and into data simulated from each of two models fit to the same real data. Using real respiratory syndrome counts collected in an emergency department from 2/1/94-5/31/03, we varied the length of training data from one to eight years, applied a sequential test to the forecast errors arising from each of eight forecasting methods, and evaluated their detection probabilities (DP) on the basis of 1000 injected synthetic outbreaks. We did the same for each of two corresponding simulated data sets. The less realistic, nonhierarchical model's simulated data set assumed that "one season fits all," meaning that each year's seasonal peak has the same onset, duration, and magnitude. The more realistic simulated data set used a hierarchical model to capture violation of the "one season fits all" assumption. RESULTS: This experiment demonstrated optimistic bias in DP estimates for some of the methods when data simulated from the nonhierarchical model was used for DP estimation, thus suggesting that at least for some real data sets and methods, it is not adequate to assume that "one season fits all." CONCLUSION: For the data we analyze, the "one season fits all " assumption is violated, and DP performance claims based on simulated data that assume "one season fits all," for the forecast methods considered, except for moving average methods, tend to be optimistic. Moving average methods based on relatively short amounts of training data are competitive on all three data sets, but are particularly competitive on the real data and on data from the hierarchical model, which are the two data sets that violate the "one season fits all" assumption.

Computer Simulation↗
PubMed2006

The structural basis of cooperative regulation at an alternate genetic switch.

Bacteriophage lambda is a paradigm for understanding the role of cooperativity in gene regulation. Comparison of the regulatory regions of lambda and the unrelated temperate bacteriophage 186 provides insight into alternate ways to assemble functional genetic switches. The structure of the C-terminal domain of the 186 repressor, determined at 2.7 A resolution, reveals an unusual heptamer of dimers, consistent with presented genetic studies. In addition, the structure of a cooperativity mutant of the full-length 186 repressor, identified by genetic screens, was solved to 1.95 A resolution. These structures provide a molecular basis for understanding lysogenic regulation in 186. Whereas the overall fold of the 186 and lambda repressor monomers is remarkably similar, the way the two repressors cooperatively assemble is quite different and explains in part the differences in their regulatory activity.

Amino Acid Substitution↗
PubMed2006

Identification of the central quorum sensing regulator of virulence in the enteric phytopathogen, Erwinia carotovora: the VirR repressor.

In the Gram-negative phytopathogen, Erwinia carotovora ssp. atroseptica (Eca) virulence depends on the production of a N-(3-oxohexanoyl)-L-homoserine lactone (OHHL) quorum sensing (QS) signal. This work identifies the elusive 'missing link' between QS and virulence in Erwinia. We have identified and characterized a novel regulator of virulence, VirR, in Eca and show that a virR mutation completely restores virulence factor production to an Eca mutant unable to synthesize OHHL. This effect of the virR mutation translates to a restoration of virulence to wild-type levels and thus provides evidence that VirR acts to prevent the production of virulence factors at low cell density. We also show that, in Eca, transcription of virulence genes is controlled by OHHL and that this control is effected through the action of VirR. We also demonstrate that the VirR regulatory pathway is present and functional in both blackleg and soft rotting species of Erwinia.

4-Butyrolactone↗
PubMed2005

Modeling emergency department visit patterns for infectious disease complaints: results and application to disease surveillance.

BACKGROUND: Concern over bio-terrorism has led to recognition that traditional public health surveillance for specific conditions is unlikely to provide timely indication of some disease outbreaks, either naturally occurring or induced by a bioweapon. In non-traditional surveillance, the use of health care resources are monitored in "near real" time for the first signs of an outbreak, such as increases in emergency department (ED) visits for respiratory, gastrointestinal or neurological chief complaints (CC). METHODS: We collected ED CCs from 2/1/94 - 5/31/02 as a training set. A first-order model was developed for each of seven CC categories by accounting for long-term, day-of-week, and seasonal effects. We assessed predictive performance on subsequent data from 6/1/02 - 5/31/03, compared CC counts to predictions and confidence limits, and identified anomalies (simulated and real). RESULTS: Each CC category exhibited significant day-of-week differences. For most categories, counts peaked on Monday. There were seasonal cycles in both respiratory and undifferentiated infection complaints and the season-to-season variability in peak date was summarized using a hierarchical model. For example, the average peak date for respiratory complaints was January 22, with a season-to-season standard deviation of 12 days. This season-to-season variation makes it challenging to predict respiratory CCs so we focused our effort and discussion on prediction performance for this difficult category. Total ED visits increased over the study period by 4%, but respiratory complaints decreased by roughly 20%, illustrating that long-term averages in the data set need not reflect future behavior in data subsets. CONCLUSION: We found that ED CCs provided timely indicators for outbreaks. Our approach led to successful identification of a respiratory outbreak one-to-two weeks in advance of reports from the state-wide sentinel flu surveillance and of a reported increase in positive laboratory test results.

Bioterrorism↗
PubMed2005

Identification of a new quorum-sensing-controlled virulence factor in Erwinia carotovora subsp. atroseptica secreted via the type II targeting pathway.

Two-dimensional polyacrylamide gel electrophoresis of the secreted proteins of Erwinia carotovora subsp. atroseptica revealed a low-abundance protein that was identified by mass spectrometry as a homologue of a Xanthomonas campestris avirulence protein with unknown function. The predicted Svx protein has an N-terminal signal sequence and zinc binding-region signature, and the mature protein is post-translationally modified. A 2D difference gel electrophoresis (DIGE) showed that the protein is secreted by the type II (out) secretion apparatus, which is also responsible for the secretion of the major known virulence factors, PelC and CelV. Transcription of the svx gene is under N-acyl-homoserine lactone-mediated quorum-sensing control. The svx gene was inactivated by transposon insertion. The mutant showed a decrease in virulence in potato plant assays, demonstrating a role for Svx in the pathogenicity of E. carotovora subsp. atroseptica. These results show that Svx is a previously unidentified virulence determinant which is secreted by the out machinery and is regulated by quorum sensing, two systems employed by several other virulence factors. Thus, the type II secretory machine is a conduit for virulence factors other than the main pectinnases and cellulase in E. carotovora subsp. atroseptica.

Bacterial Proteins↗
PubMed2004

Cooperativity in long-range gene regulation by the lambda CI repressor.

Effective repression of cI transcription from PRM by the bacteriophage lambda CI repressor requires binding sites (OL) located 2.4 kb from the promoter. A CI tetramer bound to OL1.OL2 interacts with a tetramer bound near PRM (OR1.OR2), looping the intervening DNA. We previously proposed that in this CI octamer:DNA complex, the distant OL3 operator and the weak OR3 operator overlapping PRM are juxtaposed so that a CI dimer at OL3 can cooperate with a CI dimer binding to OR3. Here we show that OL3 is necessary for effective repression of PRM and that the repressor at OL3 appears to interact specifically with the repressor at OR3. The OL3-CI-OR3 interaction involves the same CI interface used for short-range dimer-dimer interactions and does not occur without the other four operators. The long-range interactions were incorporated into a physicochemical model, allowing estimation of the long-range interaction energies and showing the lysogenic state to be ideally poised for CI negative autoregulation. The results establish the lambda system as a powerful tool for examining long-range gene regulatory interactions in vivo.

Binding Sites↗
PubMed2003

Results from the fielding of the Bio-surveillance Analysis, Feedback, Evaluation and Response (B-SAFER) system in Albuquerque, New Mexico.

Public health authorities need a surveillance system that is sensitive enough to detect a disease outbreak early to enable a proper response. In order to meet this challenge we have deployed a pilot component-based system in Albuquerque, NM as part of the National Biodefense Initiative (BDI). B-SAFER gathers routinely collected data from healthcare institutions to monitor disease events in the community. We describe initial results from the deployment of the system for the past 6 months

Confidentiality↗