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Search Results: 1 - 10 of 63506 matches for " John Z. Metcalfe "
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Moving Beyond Directly Observed Therapy for Tuberculosis
John Z. Metcalfe,Max R. O’Donnell?,David R. Bangsberg
PLOS Medicine , 2015, DOI: 10.1371/journal.pmed.1001877
A Transcriptional Signature for Active TB: Have We Found the Needle in the Haystack?
Adithya Cattamanchi ,Nicholas D. Walter,John Z. Metcalfe,J. Lucian Davis
PLOS Medicine , 2013, DOI: 10.1371/journal.pmed.1001539
Microscopic-Observation Drug-Susceptibility Assay for the Diagnosis of Drug-Resistant Tuberculosis in Harare, Zimbabwe
Beauty Makamure, Jesca Mhaka, Salome Makumbirofa, Reggie Mutetwa, Lucy Mupfumi, Peter Mason, John Z. Metcalfe
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0055872
Abstract: Introduction Limited data exist on use of the microscopic-observation drug-susceptibility (MODS) assay among persons suspected of MDR-TB living in high HIV-prevalence settings. Methods We retrospectively reviewed available clinical and drug susceptibility data for drug-resistant TB suspects referred for culture and drug-susceptibility testing between April 1, 2011 and March 1, 2012. The diagnostic accuracy of MODS was estimated against a reference standard including L?wenstein-Jensen (LJ) media and manual liquid (BACTEC MGIT) culture. The accuracy of MODS drug-susceptibility testing (DST) was assessed against a reference standard absolute concentration method. Results One hundred thirty-eight sputum samples were collected from 99 drug-resistant TB suspects; in addition, six previously cultured MDR isolates were included for assessment of DST accuracy. Among persons with known HIV infection status, 39/59 (66%) were HIV-infected. Eighty-six percent of patients had a history of prior TB treatment, and 80% of individuals were on antituberculous treatment at the time of sample collection. M. tuberculosis was identified by reference standard culture among 34/98 (35%) MDR-TB suspects. Overall MODS sensitivity for M. tuberculosis detection was 85% (95% CI, 69–95%) and specificity was 93% (95% CI, 84–98%); diagnostic accuracy did not significantly differ by HIV infection status. Median time to positivity was significantly shorter for MODS (7 days; IQR 7–15 days) than MGIT (12 days; IQR 6–16 days) or LJ (28 days; IQR 21–35 days; p<0.001). Of 33 specimens with concurrent DST results, sensitivity of the MODS assay for detection of resistance to isoniazid, rifampin, and MDR-TB was 88% (95% CI, 68–97%), 96% (95% CI, 79–100%), and 91% (95% CI, 72–99%), respectively; specificity was 89% (95% CI, 52–100%), 89% (95% CI, 52–100%), and 90% (95% CI, 56–100%), respectively. Conclusion In a high HIV-prevalence setting, MODS diagnosed TB and drug-resistant TB with high sensitivity and shorter turnaround time compared with standard culture and DST methods.
Rapid Molecular Testing for TB to Guide Respiratory Isolation in the U.S.: A Cost-Benefit Analysis
Alexander J. Millman, David W. Dowdy, Cecily R. Miller, Robert Brownell, John Z. Metcalfe, Adithya Cattamanchi, J. Lucian Davis
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0079669
Abstract: Background Respiratory isolation of inpatients during evaluation for TB is a slow and costly process in low-burden settings. Xpert MTB/RIF (Xpert) is a novel molecular test for tuberculosis (TB) that is faster and more sensitive but substantially more expensive than smear microscopy. No previous studies have examined the costs of molecular testing as a replacement for smear microscopy in this setting. Methods We conducted an incremental cost–benefit analysis comparing the use of a single negative Xpert versus two negative sputum smears to release consecutive adult inpatients with presumed TB from respiratory isolation at an urban public hospital in the United States. We estimated all health-system costs and patient outcomes related to Xpert implementation, diagnostic evaluation, isolation, hospitalization, and treatment. We performed sensitivity and probabilistic uncertainty analyses to determine at what threshold the Xpert strategy would become cost-saving. Results Among a hypothetical cohort of 234 individuals undergoing evaluation for presumed active TB annually, 6.4% had culture-positive TB. Compared to smear microscopy, Xpert reduced isolation bed utilization from an average of 2.7 to 1.4 days per patient, leading to a 48% reduction in total annual isolation bed usage from 632 to 328 bed-days. Xpert saved an average of $2,278 (95% uncertainty range $1582–4570) per admission, or $533,520 per year, compared with smear microscopy. Conclusions Molecular testing for TB could provide substantial savings to hospitals in high-income countries by reducing respiratory isolation usage and overall length of stay.
The lifespan for 3-dimensional quasilinear wave equations in exterior domains
John Helms,Jason Metcalfe
Mathematics , 2012,
Abstract: This article focuses on long-time existence for quasilinear wave equations with small initial data in exterior domains. The nonlinearity is permitted to fully depend on the solution at the quadratic level, rather than just the first and second derivatives of the solution. The corresponding lifespan bound in the boundaryless case is due to Lindblad, and Du and Zhou first proved such long-time existence exterior to star-shaped obstacles. Here we relax the hypothesis on the geometry and only require that there is a sufficiently rapid decay of local energy for the linear homogeneous wave equation, which permits some domains that contain trapped rays. The key step is to prove useful energy estimates involving the scaling vector field for which the approach of the second author and Sogge provides guidance.
Clinical and Radiographic Factors Do Not Accurately Diagnose Smear-Negative Tuberculosis in HIV-infected Inpatients in Uganda: A Cross-Sectional Study
J. Lucian Davis,William Worodria,Harriet Kisembo,John Z. Metcalfe,Adithya Cattamanchi,Michael Kawooya,Rachel Kyeyune,Saskia den Boon,Krista Powell,Richard Okello,Samuel Yoo,Laurence Huang
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0009859
Abstract: Although World Health Organization guidelines recommend clinical judgment and chest radiography for diagnosing tuberculosis in HIV-infected adults with unexplained cough and negative sputum smears for acid-fast bacilli, the diagnostic performance of this approach is unknown. Therefore, we sought to assess the accuracy of symptoms, physical signs, and radiographic findings for diagnosing tuberculosis in this population in a low-income country with a high incidence of tuberculosis.
Bounds on the distribution of the number of gaps when circles and lines are covered by fragments: Theory and practical application to genomic and metagenomic projects
John Moriarty, Julian R Marchesi, Anthony Metcalfe
BMC Bioinformatics , 2007, DOI: 10.1186/1471-2105-8-70
Abstract: We give bounds on the probability distribution of the number of gaps when a circle is covered by fragments of fixed size. The absolute error in the approximation is typically on the order of 0.1% at 10× coverage depth. The method can be applied to coverage problems on the interval, including edge effects, and applications are given to metagenomic libraries and shotgun sequencing.The question of how a circle becomes covered when random arcs are marked off has arisen repeatedly in bioinformatics. As an example, a prokaryotic chromosome is typically circular and the clones extracted from it for genomic libraries or shotgun sequencing projects are randomly positioned arcs. The number of uncovered gaps is of particular interest: a genomic library ideally has no gaps, while one might seek to stop the undirected part of a shotgun sequencing project when a small number of gaps remain (we call this the 'stopping problem'). Coverage problems also arise in the culture-independent methods of metagenomics, since the number of clones coming from each genome in a mixed community is random. Accordingly, the question of the number of gaps has been treated by many authors, in both mathematical and biological contexts.We refer the reader to [1] for a review of the mathematical literature on circle covering problems and the exact distribution of the number of gaps when all arcs are of equal length. Driven by practical considerations, approximate distributions for the number of gaps have been given in the genomics literature: see for example [2-4]. These approximate distributions are easier to compute than the exact distributions. Some address modified coverage problems with particular biological relevance, such as the 'edge effects' which arise when certain arc positions cannot occur. Bounds for the probability of completely covering the circle are given in [5], but to the knowledge of the authors no bounds have been given for the distribution of the number of gaps. In this paper we gi
Almost Global Existence for 4-Dimensional Quasilinear Wave Equations in Exterior Domains
John A. Helms,Jason L. Metcalfe
Mathematics , 2014,
Abstract: This article focuses on almost global existence for quasilinear wave equations with small initial data in 4-dimensional exterior domains. The nonlinearity is allowed to depend on the solution at the quadratic level as well as its first and second derivatives. For this problem in the boundaryless setting, H\"{o}rmander proved that the lifespan is bounded below by $\exp(c/\epsilon)$ where $\epsilon>0$ denotes the size of the Cauchy data. Later Du, the second author, Sogge, and Zhou showed that this inequality also holds for star-shaped obstacles. Following up on the authors' work in the 3-dimensional case, we weaken the hypothesis on the geometry and only require that the obstacle allow for a sufficiently rapid decay of local energy for the linear homogeneous wave equation. The key innovation of this paper is the use of the boundary term estimates of the second author and Sogge in conjunction with a variant of an estimate of Klainerman and Sideris, which will be obtained via a Sobolev inequality of Du and Zhou.
Pharmaceutical Compounds in Wastewater: Wetland Treatment as a Potential Solution
John R. White,Marco A. Belmont,Chris D. Metcalfe
The Scientific World Journal , 2006, DOI: 10.1100/tsw.2006.287
Active feedback of a Fabry-Perot cavity to the emission of a single InAs/GaAs quantum dot
Michael Metcalfe,Andreas Muller,Glenn S. Solomon,John Lawall
Physics , 2010, DOI: 10.1364/JOSAB.26.002308
Abstract: We present a detailed study of the use of Fabry-Perot (FP) cavities for the spectroscopy of single InAs quantum dots (QDs). We derive optimal cavity characteristics and resolution limits, and measure photoluminescence linewidths as low as 0.9 GHz. By embedding the QDs in a planar cavity, we obtain a sufficiently large signal to actively feed back on the length of the FP to lock to the emission of a single QD with a stability below 2% of the QD linewidth. An integration time of approximately two seconds is found to yield an optimum compromise between shot noise and cavity length fluctuations.
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